Relationship between subclasses of serum HDL and LPL gene HindⅢ polymorphism in hyperlipidemia

AIM: To investigate lipoprotein lipase gene HindⅢ polymorphism and its relationship with serum lipids and apolipoprotein, serum HDL subclasses in patients with hyperlipoidemia. METHODS: Lipoprotein lipase gene HindⅢ polymorphism was assayed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The subclasses of serum HDL in 152 hyperlipoidemia patients and 128 healthy subjects were determined by two-dimensional gel electrophoresis conjunction with immunodetection method. RESULTS: H+H+ genotype and allele H+ in hyperlipoidemia and control groups were both the highest. In hyperlipidemia group, H+H+ genotypes tended to be higher than that in control group, while H+H- and H-H- genotypes were significantly lower (P<0.05). In hyperlipidemia group allele H+ carriers' frequency tended to be higher than that in control group (P<0.05). In hyperlipoidemia group, the genotype of H+H+ showed higher serum TG, apoB100 levels, TG/HDL-C ratio, preβ1-HDL, HDL3b and lower HDL2a, HDL2b compared with H-H- (P<0.05). In control group, the genotype of H+H+ had higher serum TG，HDL3c and lower HDL2a compared with H-H- (P<0.05). CONCLUSION: The HindⅢ polymorphism at intron 8 of LPL gene is associated with the general shift toward smaller size of HDL particle size in hyperlipoidemia, and the change of HDL subclasses distribution profile may be closely related to the pathogenesis of atherosclerosis in Chinese patients with hyperlipoidemia.     

Relationship of subclasses of serum HDL and Apo A-Ⅰ gene polymorphism in hyperlipidemia

AIM: To investigate apolipoprotein A-Ⅰ gene (Apo A-Ⅰ) polymorphism and its relationship with serum HDL subclasses in patients with hyperlipidemia (HL). METHODS: Apo A-Ⅰ genotype was assayed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The subclasses of serum HDL in 118 patients with hyperlipidemia and 109 healthy subjects were determined by two-dimensional gel electrophoresis conjunction with immunodetection method. RESULTS: Both in HL group and the control group, G/G and C/C genotypes were the most frequent at －78 bp and ＋83 bp of Apo A-Ⅰ gene, respectively. The frequency of rare A allele at －78 bp in HL group was significantly higher than that in control group. In HL group, subjects with G/A mutation had higher serum levels of TG, Apo C-Ⅲ, pre β1-HDL and HDL3a, and lower levels of HDL2a and HDL2b compared to the subjects with G/G genotype. CONCLUSION: The G/A transition in the －78 bp position of the Apo A-Ⅰ gene promoter in patients with hyperlipidemia is associated with HDL subclasses. There is a general shift toward smaller sized HDL, which, in turn, indicates that HDL maturation might be abnormal.     

Influences of apolipoprotein CII concentrations on high-density lipoprotein subclass distribution

AIM: To investigate the influence of serum apolipoprotein (apo) CII concentrations on the distribution of serum high-density lipoprotein (HDL) subclasses. METHODS: Serum HDL subclasses in 247 subjects were determined by two dimensional gel electrophoresis-immunodetection. RESULTS: With the increase in serum apolipoprotein CII levels, age, BMI, the contents of TG, TC, apoB100, apoCII, apoCIII, apoE, preβ1-HDL, preβ2-HDL, HDL3b and HDL3a increased significantly, but the contents of HDL-C, HDL2a and HDL2b decreased remarkably. The contents of preβ1-HDL increased with the rise in apoCII and apoA I levels, whereas the content of HDL2b increased with the rise in serum apoA I level in the same apoC II group, but decreased with the increase in serum apolipoprotein CII level in the same apoA I group. With the increase in the ratio of apoCII/ apoCIII, the content of preβ1-HDL elevated, but the content of HDL2b decreased. The correlation analysis illustrated that the apoCII level was positively correlated with preβ1-HDL (r=0.186, P<0.01), but inversely correlated with HDL2b (r=-0.149, P<0.05). The apoA I level was positively associated with all HDL subclasses (r in the range of 0.349-0.587, P<0.01). In addition, the apoCIII level was positively correlated with preβ1-HDL (r=0.184, P<0.01) and preβ2-HDL (r=0.178, P<0.01), while the apoE level was positively correlated with HDL3a (r=0.040, P<0.05). The apoB100 level was inversely correlated with HDL2a (r=-0.102, P<0.05). CONCLUSION: The particles of HDL show a general shift towards smaller size with the increase in apoCII levels, indicating that the maturation of HDL is abnormal. Whereas the contents of apoA I level correct the effect of apoCII on the distribution profile of HDL subclasses. The ratio of apoCII/apoCIII might also been taken as one of the indexes reflecting the distribution profile of serum HDL subclasses.     

Subclasses of serum HDL in middle and old aged patients with hyperlipidemia in Chengdu City

AIM: To detect the change of composition and ratio of serum HDL subclasses and explore the relationship between these changes and the plasma lipid level in patients with hyperlipidemia. METHODS: The components of subclasses of serum HDL in 172 middle and old aged patients with hyperlipidemia and 115 healthy middle and old aged were determined by dimensional gel electrophoresis associated with immuno-blotting method. RESULTS: Compared to the healthy controls, the contents of pre β1-HDL，　HDL3b and HDL3a were significantly higher (P＜0.05 or P＜0.01), while that of HDL2b was significantly lower (P＜0.01) in middle and old aged patients with hyperlipidemia. The content of pre β1-HDL increased with age in healthy controls, whereas the HDL2b decreased. The content of pre β1-HDL was significantly higher (P＜0.05), while the HDL2b (P＜0.05) was significantly lower in men than in women in patients with hyperlipidemia and the healthy controls. In middle and old aged patients with hyperlipidemia, the content of pre β1-HDL was positively correlated with the serum TG, TC, apoB100, apoCⅡ, apoCⅢ, apoE and TG/HDL-C (r=0.432; r=0.243; r=0.341; r=0.259; r=0.335; r=0.308 and r=0.453, P＜0.05 or P＜0.01), while it was negatively correlated with HDL-C (r=－0.167, P＜0.05). The content of HDL2b was negatively correlated with TG, TC, apoCⅡ, apoCⅢ and TG/HDL-C (r=－0.296; r=－0.156; r=－0.182; r=－0.216; r=－0.203 and r=－0.313, P＜0.05 or P＜0.01), while it was positively correlated with HDL-C (r=0.124, P＜0.05). CONCLUSIONS: The particle of HDL in the middle and old aged patients with hyperlipidemia showed a general shift towards smaller size, which indicated that the reverse cholesterol transport might be weakened. Men had smaller HDL particle size than women.     

Relationship between HDL subclasses and TC/HDL-C,TG/HDL-C ratio

AIM: To study the relationship between HDL subclasses and TC/HDL-C, TG/HDL-C ratio in serum. METHODS: Apolipoprotein (apo) A-Ⅰ contents of serum HDL subclasses in 292 subjects were determined by two-dimensional gel electrophoresis associated with immunodection method. RESULTS: Compared with low TC/HDL-C ratio subgroup, apoA-Ⅰcontents of preβ1-HDL (P<0.01, in middle or high subgroup) and HDL3a (P<0.05, in high subgroup) were significantly higher, but those of HDL2b (P<0.01, in middle or high subgroup) and HDL2a (P<0.01, in high subgroup) were significantly lower. Compared with middle TC/HDL-C ratio subgroup, apoA-Ⅰ contents of preβ1-HDL, HDL3a were significantly higher (P<0.01, P<0.05), but those of HDL2a and HDL2b were significantly lower (P<0.01, P<0.01) in high subgroup. Compared with low TG/HDL-C ratio subgroup, apoA-Ⅰ contents of preβ1-HDL, HDL3a were significantly higher (P<0.01, P<0.05, in high subgroup), but those of HDL2a and HDL2b were significantly lower (P<0.01, in middle or high subgroup). Compared with middle TG/HDL-C ratio subgroup, apoA-Ⅰ contents of preβ1-HDL, HDL3a were significantly higher (P<0.01, P<0.05), but those of HDL2a and HDL2b were significantly lower (P<0.01). In addition, TC, TG, TC/HDL-C ratio and TG/HDL-C ratio showed a positive correlation with apoA-Ⅰ contents of small-sized preβ1-HDL and a negative correlation with those of large-sized HDL2b, but it was reversed for HDL-C. CONCLUSION: When TC/HDL-C>5 or TG/HDL-C>2.2 in serum, the particle size of HDL shifted towards smaller sizes, which indicates that reverse cholesterol transport might be weakened and HDL maturation might be abnormal.     

Association of F XⅢVal34Leu with coronary heart disease

AIM: To investigate the distribution of coagulation factor XⅢ (FXⅢ) Val34Leu polymorphism in Chinese and the relationship between the polymorphism and coronary heart disease (CHD) or myocardial infarction. METHODS: A total of 195 patients with angiographically confirmed CHD and 203 controls were genotyped for the Val34Leu polymorphism by polymerase chain reaction-single strand conformational polymorphism (PCR-SSCP) analysis. RESULTS: The FXⅢ Val34Leu was found in 19 out of all 398 samples (4.8%) representing a Leu allele frequency of 2.4%. The distribution of FXⅢ genotype and allele was not significantly different between all patients and controls (P>0.05). The Val/Leu genotype and Leu allele frequencies in subjects without MI were significantly higher than that in subjects with MI (P<0.05). CONCLUSION: There is F XⅢ Val34Leu polymorphism in Han ethnic group.     

The interrelationships between serum HDL subpopulations and triacyglycerol

AIM: To Study the influence of plasma TG level on the contents of serum HDL subpopulations. METHODS: Classified by the contents of serum TG, the serum level of HDL subpopulations in 106 normal TC and 183 high TC subjects were analyzed by two-dimensional gel electrophoresis coupled with immunodection method. RESULTS: The apo-AⅠcontents of per-β1-HDL, HDL3c, HDL3b and HDL3a were higher in a certain extent in TC high subjects vs corresponding TC desirable subjects. The apo-AⅠ contents of per-β1-HDL （in borer-line high TG subgroup） and HDL3b （in very high TG subgroup） were significantly higher (P<0.05 or P<0.01), while the apo-AⅠ contents of HDL2b and HDL2a were all lower in TC high subjects vs corresponding TC normal subjects. With the increase in plasma TG levels, the apoA-Ⅰ content of pre-β1-HDL increased, and it was significantly higher (P<0.05 or P<0.01) in borderline-high TG(except TC desirable subjects), high TG and very high TG subgroups vs corresponding normal TG subgroup. Contents of HDL3b and HDL3a had the same tendency, and in TC high subjects contents of HDL3b (in very high TG subgroup) and HDL3a (in every subgroups, in which levels of TG were higher) were significantly higher (P＜0.05 and P＜0.01） than in normal TG subgroup. On contrast, the apoA-Ⅰcontents of HDL2b and HDL2a following with the increase of plasma TG levels tended to become lower. Contents of HDL2b were significantly lower (P<0.05) in high TG subgroup and very high TG subgroup vs corresponding normal TG subgroup, and in TC high subjects contents of HDL2a were significantly lower (P<0.05) in very high TG subgroups vs normal TG subgroup. CONCLUSION: Our data show the general shift toward smaller size of HDL particle size with the increase in TC and TG levels. Contents of TC and TG are very important to contents of HDL subclasses.     

Relationship between apolipoprotein E gene polymorphism and sporadic Alzheimer's disease

AIM: To evaluate the association between apolipoprotein E(apoE) gene polymorphism and sporadic Alzheimer's disease (AD). METHOD: A case-control study was undertaken detecting the polymorphism of apoE by polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP).RESULTS:(1)The frequencies of 3/4 genotype and 4 al ele in AD were significant ly higher than that in age-matched controls(P<0.05).(2)The frequency of G/G genotype for apoE IE1 in AD was significantly higher than that in age-mat ched control(P<0.05).(3)The apoE 4 al ele was associated with a tripling of the risk for AD compared with no 4 allele(odd ratio 2.932, 95%CI 1.379~6.226);Homozygosity of the G allele in IE1 was associated with adoubling of the risk for AD compared with the G/C and C/C genotypes(odd rat io 2.223, 95%CI 1.075~4.599).However, the IE1 G al ele is also closely associated with apoE 4.When the sample was split on the basis of apo Egenotype, the associat ion between IE1 G/G genotype and AD was no longer statistically significant.CONCLUSION: ApoE ε4 was a risk factor of AD, and the apparent association between IE1 G/G and AD is a consequence of the association between the ε4 and IE1 G/G genotype.     

Relationship between the E-selectin and oxidative stress in patients with obese type 2 diabetes mellitus

AIM: To investigate the relationship between the levels of soluble E-selectin and oxidative stress in patients with obese type 2 diabetes mellitus.METHODS: The level of E-selectin, the contents of ox-LDL and malondialdehyde (MDA) and activities of superoxide dismutase (SOD) were measured in patients with obese and non-obese type 2 diabetes mellitus.RESULTS: The levels of E-selectin, ox-LDL and MDA were higher in patients with obese type 2 diabetes mellitus than those in control group (P<0.05), and the contents of HDL-C, HDL2-C and HDL3-C were significantly lower than those in control group (P<0.01).The activity of SOD in patients with obese type 2 diabetes mellitus was significantly lower than that in control group.The contents of E-selectin and MDA were more markedly elevated in patients with obese type 2 diabetes mellitus than those in patients with non-obese type 2 diabetes mellitus (P<0.01,P<0.05) and the activity of SOD was also significantly lower than that in patients with non-obese type 2 diabetes mellitus (P<0.01).There was significantly positive correlation between E-selectin and HbA1c, waist circumference, TC, ox-LDL, MDA (r=0.352, P<0.05;r=0.634, P<0.05;r=0.517, P<0.05;r=0.480, P<0.05;r=0.572, P<0.05), and negatively correlation between E-selectin and HDL3-C (r=-0.374, P<0.05).CONCLUSION: The plasma level of E-selectin is markedly elevated in patients with obese type 2 diabetes mellitus.E-selectin is possibly associated with oxidative stress.     

High density lipoprotein subclasses and activities of protein kinase C

AIM: To investigate the relationship between high density lipoprotein (HDL) subclasses and the binding activities of hepatic cell and extra-hepatic cell HDL receptor and intracellular protein kinase C (PKC). METHODS: Using purified pre-β1 HDL and apoE-deficent HDL3 to react with human smooth muscle cells (SMC) and HepG2 cells, then the activities of pre-β1HDL and apoE-deficent HDL3 binding to SMC and HepG2 cells, and the effects of this two HDL subclasses on PKC activities in SMC and HepG2 cells were observed . RESULTS: The results showed that the value of Kd of pre-β1HDL binding to SMC HDL receptor was not only significantly lower than that of apoE-deficient HDL3 (P<0.05), but significantly lower than pre-β1 HDL binding to HepG2 HDL receptor (P<0.05). Cell PKC system was all activated by binding of the two HDL subclasses with SMC HDL receptor, and the effect of pre-β1HDL appeared to be stronger than apoE-deficent HDL3. No change in HepG2 cell PKC activity by binding the two HDL subclasses with HepG2 HDL receptor was observed. CONCLUSIONS: The results indicate that the ability of pre-β1HDL to promote efflux of cholesterol from extra-hepatic cells is stronger than that of apoE-deficent HDL3, and it seems that plasma pre-β1 HDL mainly interacts with extra-hepatic cell HDL receptor, subsequently, activates PKC signal transduction system and promotes the intracellular cholesterol efflux from cells.     

Relationship between polymorphism of angiotensin I converting enzyme gene insertion/deletion and ACE,PAI-1 activity in patients with myocardial infarction

AIM:To explore the relationship between polymorphism of angiotensin I converting enzyme gene insertion/deletion (I/D) and ACE, PAI-1 activity in patients with myocardial infarction (MI). METHODS:Ninety-three patients with MI and eighty-seven healthy controls were tested. ACE genomic DNA was amplified using the polymerase chain reaction (PCR). Serum ACE activity was measured by colorimetry, plasma level of PAI-1 activity was determined by spectrophotometric assay. RESULTS:① The frequency of ACE DD genotype and D alleles (32.3% and 54.3%) in MI group was significantly higher than those in control group (12.6% and 37.4%, P<0.01, respectively). ② The ACE activity in serum (216.00±58.26)U/L and plasma PAI-1 activity (0.85±0.19)AU/mL in MI group were significantly higher than those in control group (170.19±48.99)U/L, (0.66±0.20)AU/mL, P<0.01, respectively. The serum ACE activity was positively correlated with plasma PAI-1 activity both in MI group and control group (r=0.7108 and r=0.7829;P<0.01, respectively). ③ In MI group, the serum ACE activity and plasma PAI-1 activity showed a significantly higher level in subjects with DD genotype (251.64±57.76)U/L, (0.96±0.16)AU/mL than those with ID (211.47±51.87)U/L, (0.82±0.18) AU/mL and Ⅱ genotypes (179.84±52.65)U/L, (0.71±0.17)AU/mL. The serum ACE activity and plasma PAI-1 activity were significantly higher in subjects with ID genotype than those with II genotype (P<0.05). In control group, the serum ACE activity and plasma PAI-1 activity showed a significantly higher level in subjects with DD genotype (195.53±54.76)U/L, (0.78±0.20)AU/mL than the subjects with Ⅱ genotype (154.98±52.74)U/L, (0.59±0.17)AU/mL (P<0.05). CONCLUSION:The increased ACE activity caused by DD polymorphism may play an important role in elevating the level of plasma PAI-1. The DD genotype of ACE is associated with high PAI-1 level. The genetic variation of ACE contributes to the balance of fibrinolytic pathway, indicating the pathogenesis mechanisms linking to the ACE I/D genotype and MI.     

Effects of Shan He Jian Fei Granule on the expression of leptin,adiponectin and resistin in obese rats induced by high-fat feeding

AIM: To study the effects of Shan He Jian Fei Granule (SHJFG), a Chinese medicine, on weight-reduction and fat-decrease in adiposity rats, and to observe the changes of leptin, adiponectin and resistin. METHODS: After the models were prepared successfully, the rats were randomly divided into four groups: normal group, low dosage, middle dosage, high dosage and obesity control group. After 8 weeks interference with SHJFG, the weight and the naso-anal length of each rat was measured and Lees index were calculated. The levels of TG, TC, LDL, HDL and leptin in serum were carefully determined. The gene expressions of adiponectin and resistin in adipose tissues of rats were determined by RT-PCR. RESULTS: Compared to high-fat diet group, the body weights, the Lees indexes, the weight of fat tissues and levels of TG, TC, LDL and leptin in SHJFG groups significantly decreased (P<0.05). Adiponectin mRNA expression in SHJFG group significantly increased (P<0.05), and the resistin mRNA expression also significantly increased. CONCLUSION: SHJFG significantly decreases the body weight and the serum levels of TG, TC and LDL in obese rats. The effects of SHJFG in raising the mRNA expressions of adiponectin and resistin in fat tissues may be one of the main role that results in lowering body weight in obese rats.     

Relationship between matrix metalloproteinase 2-735C→T genetic polymorphism in promoter region and coronary atherosclerosis

AIM: To investigate the relationship between matrix metalloproteinase 2 ( MMP-2 )-735C→T polymorphism in the promoter region and coronary atherosclerosis (CAS) in Han population of China. METHODS: This study was conducted with a CAS group including 309 patients confirmed by angiography and 311 control healthy subjects. Genotype of -735C→T functional promoter polymorphism of the MMP-2 gene was determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The relationship between the polymorphism in MMP-2 gene and CAS was analyzed. RESULTS: The frequency of CC genotype (86.1%) in CAS group was significantly higher than that in control group (79.7%), but the frequency of CT+TT genotype (13.9%) in CAS group was significantly lower than that in control group (20.3%). The statistical difference between CAS group and controls was significant(χ²=4.398,P<0.05). The frequency of -735C in CAS group (92.6%) was higher than that in control group (89.1%) and the frequency of -735T in CAS group (7.4%) was lower than that in control group (10.9%), with the statistical significant difference (χ²=4.521, P<0.05). The degree of stenosis in coronary artery did not significantly relate to the MMP-2 gene -735C→T polymorphism in the promoter region. CONCLUSION: The genetic polymorphism in MMP-2 promoter region (-735C→T) is associated with the susceptibility to CAS in Han population of China. CC genotype and C allele may be a genetic marker. The -735C→T polymorphism may be useful as a predictor of CAS.     

Relationship between blood pressure and fibrinogenic expression of fibrinogen Bβ-chain gene polymorphisms

AIM: To study the correlation between blood pressure and 6 common fibrinogen (Fg) Bβ-chain gene polymorphisms (Bβ-854G/A,-455G/A,-249C/T,-148C/T, 448G/A, Bcl-1G/A), and to investigate the effect of blood pressure on plasma fibrinogen concentration and the functional expression of fibrinogen. METHODS: 1 391 subjects from Kailuan Group Corporation were enrolled for medical examination and questionnaire survey. Venous blood were collected in the early morning to measure Fg concentration, fibrin monomer polymerized velocity (FMPV), absorbance maximum (A_max) and FMPV/A_max. The blood pressure was also measured and the subjects were accordingly divided into hypertension group (HG) and the normal blood pressure group (NG). The 6 gene polymorphisms were detected by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). RESULTS: No differences of the genotype frequencies of the 6 sites between hypertension group (HG) and normal blood pressure group (NG) were found (P>0.05). No differences of Fg concentration and FMPV/A_max between HG group and NG group were observed (P>0.05). However, FMPV and A_max in HG group were lower than those in NG group (P<0.05). In HG and NG group, the Fg concentration, FMPV, A_max, FMPV/A_max in the subjects with Bβ-854 mutated genotype were all higher than those in the subjects with wild genotype (P<0.05). In NG group, the Fg concentration and FMPV in the subjects with Bβ Bcl-1 mutated genotype were higher than those in the subjects with wild genotype (P<0.05). Fg, FMPV and A_max in the subjects with Bβ-854 and Bcl-1 mutated genotype in HG group were lower than those in NG group (P<0.05). CONCLUSION: Fg Bβ-854 is one of the main gene situs of regulating the functional expression of fibrinogen. Bcl-1 mutated genotype increases plasma Fg concentration and FMPV. Hypertension decreases the effect of this regulation, and affects the process of fibrin monomer aggregation into dimer, resulting in a special type of coagulation dysfunction.     

Relationship between 936C/T polymorphism in 3’-untranslated region of vascular endothelial growth factor gene and diabetic retinopathy in China

AIM: To study the distribution of 936C/T polymorphism in 3’- untranslated region of vascular endothelial growth factor (VEGF) gene in Chinese Han population and to analyze the relationship between the polymorphism and diabetic retinopathy (DR). METHODS: Two hundred and fifty-four patients with type 2 diabetes mellitus recruited in this study were divided into NPDR group (non-proliferative diabetic retinopathy), PDR group (proliferative diabetic retinopathy) and DM (diabetes without retinopathy) group. The normal control group consisted of 120 subjects. Genotypes were identified by PCR-RFLP among all the subjects, while other clinical parameters were measured. Serum levels of VEGF were tested by the method of ELISA. RESULTS: The frequencies of both genotype CC and allele C were significantly higher in NPDR group and PDR group than those in NC group (²=9.934, ²=4.899, P<0.05 and ²=10.895, ²=5.714, P<0.05) and DM group (²=7.490, ²=4.448, P<0.05 and ²=8.333, ²=5.227, P<0.05). However, the frequencies of genotype (TT+CT) and allele T were significantly lower in NPDR group and PDR group than those in NC group (²=9.934, ²=10.895, P<0.01 and ²=4.899, ²=5.714, P<0.05) and DM group (²=7.490, ²=8.333, P<0.01 and ²=4.448, ²=5.227, P<0.05). Multivariate logistic regression analysis showed that the levels of glycohemoglobin(HbA1c), total cholesterol(TC),low-density lipoprotein cholesterol(LDL-C) and plasma VEGF presented a positive correlation with DR, respectively, and the 936C/T mutation of VEGF exhibited a negative correlation with DR (β=-1.027, OR=0.343, P<0.01, CI: 0.157-0.723). CONCLUSION: Allele 936C of VEGF may be a genetic marker susceptible to DR, while allele 936T may be a protective genetic marker of DR. The 936C/T mutation of VEGF may be a protective factor against DR.     

Serum lipid levels and ApoB gene Xba I and 3'-VNTR polymorphisms in longevous elderly Han population in Zhejiang

AIM: To study the levels of serum lipids and the effects of apolipoprotein B (ApoB) gene Xba I-restriction fragment length polymorphism (RFLP) and 3'-variable-number tandem repeat (VNTR) polymorphism on serum lipid and apolipoprotein levels in longevous elderly Han population in Zhejiang. METHODS: Physical and laboratory examinations were performed on longevous elders, children of longevous elders, normal control people and children of non-longevous elders, and the Xba I-RFLP and 3'-VNTR polymorphism in ApoB gene were genotyped. RESULTS: The serum levels of triglyceride (TG), low-density lipoprotein cholesterol (LDL-C) and ApoB were negatively correlated with longevity (P<0.05), while the level of high-density lipoprotein cholesterol (HDL-C) was positively correlated with longevity (P<0.01). The levels of total cholesterol (TC), LDL-C and ApoB were higher and the HDL-C level was lower in the people with Xba I-RFLP X⁺X^- genotype than those in the people with Xba I-RFLP X^-X^- genotype (P<0.01). The levels of TC, TG, LDL-C and ApoB were higher and the HDL-C level was lower in the people with 3'-VNTR large allele than those in the people with 3'-VNTR minor allele (P<0.01). CONCLUSION: High TG, LDL-C and ApoB levels and low HDL-C level are not conductive to longevity. Serum lipid levels in the people with Xba I-RFLP X^-X^- genotype or 3'-VNTR minor allele are healthy and conductive to longevity.     

Relationship between HDL subclass distribution and plasma glucose and lipid levels in patients with metabolic syndrome

AIM: To investigate high-density lipoprotein(HDL) subclass distribution and to analyze the relationship between HDL subclasses with plasma glucose and lipids in metabolic syndrome(MS). METHODS: Apolipoprotein A-I(apoA-I) contents of plasma HDL subclasses were determined by two-dimensional gel electrophoresis associated with immunodetection. The concentrations of lipids and apolipoproteins in the plasma were measured by an automated biochemical analyzer. RESULTS: Compared with the controls, the levels of fasting plasma glucose(FPG), total cholesterol(TC), triglyceride(TG), low-density lipoprotein cholesterol(LDL-C), LDL-C/high-density lipoprotein cholesterol(HDL-C), apolipoprotein B₁₀₀(apoB₁₀₀), apoB₁₀₀/apoA-I, systolic blood pressure(SBP), body mass index(BMI) and HDL_3b were increased in the MS patients(P<0.05). Meanwhile, HDL-C, apoA-I and preβ₂-HDL, HDL_2a and HDL_2b were decreased in the MS patients(P<0.01). With the increase in the plasma glucose level, the contents of HDL_2a and HDL_2b were decreased in the MS patients(P<0.05), while preβ₁-HDL was increased(P<0.05). With the decrease in the HDL-C level, the content of HDL_2b was decreased in the MS patients(P<0.01), while preβ₁-HDL was increased(P<0.01). With the increase in the TG level and the decrease in the HDL-C level, the content of HDL_2b had a decreasing trend and the content of small-particle preβ₁-HDL had an increasing trend, indicating that HDL maturation metabolism was disrupted. The correlation analysis showed that FPG was negatively correlated with the levels of HDL_2a and HDL_2b, HDL-C was negatively correlated with the level of preβ₁-HDL and positively correlated with the level of HDL_2b, and TG was positively correlated with the levels of preβ₁-HDL and HDL_3b. CONCLUSION: With the increases in the plasma glucose and TG, and the decrease in HDL-C in the MS patients, HDL particles have minifying tendency, and the maturation metabolism of HDL particles is disrupted.     

Influence of obesity on first-phase insulin secretion in individuals with different glucose tolerance

AIM: To explore the influence of obesity on the first-phase insulin secretion in the individuals with different glucose tolerance. METHODS: Thirty-eight subjects with normal glucose tolerance without family history of diabetes (normal control,NC), 32 subjects with normal glucose tolerance (NGT) who were the first-degree relatives of type 2 diabetic patients, 67 patients with impaired glucose regulation (IGR) and 35 newly-diagnosed type 2 diabetic patients (T2DM) were enrolled in the study. The patients in the 4 groups were further divided into 2 subgroups: overweight/obesity and normal weight subgroups. All subjects received oral glucose-insulin release test (OG-IRT) and intravenous glucose tolerance test (IVGTT). Acute insulin response at 3~5 min (AIR3-5) was used to reflect first-phase insulin secretion,and insulin sensitivity index (ISI) was used to reflect insulin sensitivity. The influence of obesity on the islet β-cell function and insulin sensitivity in the individuals with different glucose tolerance was observed. RESULTS: The level of AIR3-5 in NC overweight/obesity subgroup was significantly higher than that in normal weight subgroup (P<0.05), while there was no significant difference between other subgroups (P>0.05). No significant difference in the level of ISI between the patients of IGR in overweight/obesity subgroup and normal weight subgroup was observed, while in the other 3 overweight/obesity subgroups, ISI was lower than that in normal weight subgroups (P<0.05). ISI was negatively correlated with body mass index and waist circumference in all groups (P<0.05). ISI was also positively correlated with AIR3-5 in NC group and negatively correlated in the other 3 groups (P<0.05). CONCLUSION: The impact of obesity on insulin secretion is not the same in the subjects with different glucose tolerance. With the aggravation of insulin resistance, the first-phase insulin secretion in the subjects with normal glucose tolerance without family history of diabetes increases for compensation, while that in the normal glucose tolerance subjects who are the first-degree relatives of type 2 diabetic patients, the patients with impaired glucose regulation and the type 2 diabetic patients could not increase for compensation.     

Correlation of adiponectin gene SNP+45 T/G polymorphism with coronary heart disease

AIM: To investigate the relationship between adiponectin gene SNP+45 polymorphism and coronary heart disease (CHD) in south China Han population. METHODS: The nondiabetic CHD patients diagnosed by the coronary angiography were selected as CHD subjects (153 cases), and 73 healthy adults served as normal control subjects. The polymerase chain reaction- restriction fragment length polymorphism (PCR-RFLP) was performed to identify the distribution pattern of adiponectin gene SNP+45 in all subjects. The levels of plasma adiponectin were measured by ELISA. RESULTS: The frequency of T/G + G/G genotype and G allele in CHD patients were significantly higher than those in control subjects (P<0.05). Logistic regression analysis revealed that the adiponectin gene SNP+45 T/G+G/G genotype had a strong positive association with CHD (OR: 2.132, 95.0% CI: 1.034-4.397, P＜0.05). The plasma adiponectin was negatively associated with CHD (OR: 0.868, 95.0% CI: 0.785-0.959, P<0.05). CONCLUSION: The T/G+ G/G genotype was a possible risk factor for CHD in southern China Han population.     

Effects of intranasal Escherichia coli on glucolipid metabolism in high-fat diet-induced obese mice

AIM: To study whether the pulmonary infection of Escherichia coli (E. coli) interferes the glucolipid metabolism in high-fat diet-induced obese mice. METHODS: High-fat diet-induced obese mice (n=48) and normal chow-fed control mice (n=48) were intranasally infused with 40 μL fluid containing 4×10⁹ CFUs E. coli. The serum, periepididymal adipose tissue and liver were obtained at 0 d, 1 d, 2 d, 3 d and 4 d after infection. The body mass, periepididymal adipose tissue and liver were weighed, and the levels of fasting blood glucose (FBG), fasting blood insulin (FINS), free fatty acid (FFA) and very-low-density lipoprotein (VLDL) were measured by ELISA. The serum total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C), and hepatic TG contents were detected, and the hepatic steatosis was observed under microscope with oil red O staining. RESULTS: Compared with day 0, the body mass, fat mass and fat index were decreased significantly from day 1 to day 4 after infection (P<0.05). The levels of FBG, FINS and HOMA-IR were apparently raised from day 2 to day 4 after infection (P<0.05). The contents of serum FFA, TG and VLDL were increased markedly from day 1 to day 4 after infection (P<0.05). However, the concentrations of serum TC, LDL-C and HDL-C were decreased obviously from day 1 to day 3 (P<0.05). The liver mass, liver index and TG content were significantly increased from day 1 to day 4 (P<0.05). Consistently, the lipid droplet accumulation in the liver cells was increased obviously at day 2 and day 4 after infection. Compared with control group, except the levels of serum TC, LDL-C and HDL-C in obese group substantially decreased, the other indexes were increased by different degrees during the whole experiment period (P<0.05). CONCLUSION: Pulmonary infection of Escherichia coli exacerbates the disorder of glucose and lipid metabolism in high-fat diet-induced obese mice, which contributes the development of insulin resistance and hepatic steatosis.