Association between survivin promoter -31C/G polymorphism and genetic susceptibility to sporadic colorectal cancer

AIM: To investigate the association between -31C/G polymorphism in the promoter of survivin gene and the susceptibility to sporadic colorectal cancer (CRC) in southern Chinese population. METHODS: survivin -31C/G genotypes were determined by PCR-RFLP in 711 healthy controls and 702 CRC cases. RESULTS: The number of CRC patients carrying with CC genotype was much higher than that of controls (36.5 % vs 26.2%,2 =17.89,P<0.01). Compared to CC genotypes, CG, GG genotypes and G allele carriers had a significantly decreased risk of CRC, with the decrease being 0.61-fold (95% confidence interval=0.46-0.80, P<0.01), 0.52-fold (95% confidence interval=0.38-0.71,P<0.01) and 0.58-fold (95% confidence interval=0.45-0.74, P<0.01), respectively. CONCLUSION: survivin gene -31C/G polymorphism is associated with sporadic CRC risk, the G variant genotype is the independent protective factors against sporadic CRC in southern Chinese population.     

Investigating the correlation between MTDH/AEG-1 gene 5'-UTR polymorphism and genetic susceptibility to sporadic colorectal cancer

AIM: To assess the correlation between MTDH/AEG-1 gene 5'-UTR polymorphism and genetic susceptibility to sporadic colorectal cancer (CRC) in southern Chinese population by TaqMan-MGB fluorescence probes. METHODS: A case-control study was carried out on southern Chinese population to collect blood DNA samples (693 sporadic CRCs and 660 controls respectively) to investigate MTDH/AEG-1 gene 5'-UTR polymorphism by TaqMan-MGB probes. RESULTS: The distribution of MTDH/AEG-1 5'-UTR genotypes (-1 913C/G,-797G/A) had no significance between CRCs and controls. But GG genotype of -1 913C/G could increase the susceptibility of CRC in drinker(OR=1.71,95%CI=1.13-2.57) and female(OR=1.48, 95%CI= 1.01-2.17), -1 913GG had interaction with drinking and female gender to increase the risk of CRC( P<0.01); Mutated genotypes of -797(GA+AA) also could increase the susceptibility of CRC in drinker (OR=1.55,95%CI= 1.06-2.27) and person with family history of cancer(OR=3.48,95%CI= 1.60-7.57), -797(GA+AA) had interaction with drinking and positive family history of cancer to increase the risk of CRC( P<0.01). But both polymorphisms were not interacted with age, smoking and fatness. CONCLUSION: MTDH/AEG-1 gene 5'-UTR polymorphism has no significant relevance with sporadic CRC susceptibility, but is irrelevant with drinking, gender and family history of cancer to increase the risk of CRC.     

Distribution characteristics of polymorphisms of interleukin-22 gene in Guangxi population and their association with serum lipid levels

AIM: To investigate the distribution characteristics of interleukin-22 (IL-22) gene rs2227485C/T and rs2227491A/G polymorphisms in Guangxi people and the distribution differences with other ethnic groups, and to explore the difference levels of common lipid indexes in different genotypes. METHODS: SNaPshot technique and DNA sequencing were used in 280 Guangxi persons to examine IL-22 genotypes and to analyzed the distribution frequencies of allele and genotype in these sites. The distribution frequencies in different sexes, and the differences between groups and diffe-rence levels of common lipid indexes in different genotypes were analyzed statistically. RESULTS: Three genotypes of CC, CT and TT were found in rs2227485C/T with the frequency distribution of 17.1%, 49.3% and 33.6%, respectively. No significant difference between different sexes of each genotype and allele frequency in the Guangxi population was observed (P>0.05). Compared with the distribution frequencies of genotype and allele in HapMap-TSI, HapMap-HCB, HapMap-JPT and HapMap-MEX, those in Guangxi population showed statistically significant differences (P<0.05). Three genotypes of AA, AG and GG were found in rs2227491A/G with the frequency distribution of 16.1%, 52.8% and 31.1%, respectively. There was no significant difference between different sexes of each genotype and allele frequency in the Guangxi population (P>0.05). The significant differences of genotype frequencies among Guangxi population, HapMap-TSI, HapMap-JPT and HapMap-MEX were detected (P<0.05). Compared with the other 4 populations, allele frequencies in Guangxi population had significant difference (P <0.05). There were significant differences in the levels of HDL-C and LDL-C among the 3 genotypes of rs2227491A/G. The level of HDL-C had difference between AG/AA genotype and GG genotype. In addition, the level of LDL-C had difference between AG/GG genotype and AA genotype (P<0.05). CONCLUSION: rs2227485C/T and rs2227491A/G polymorphisms of IL-22 gene have differences in different populations. The rs2227491A/G polymorphism may be associated with serum lipid levels.     

Expression of IL-1α and TNF-α modified by Toll-like receptor 4 genetic polymorphism is associated with colorectal carcinoma

AIM: To investigate the association of D299G, T399I and A896G polymorphisms of Toll-like receptor 4 (TLR4) and colorectal carcinoma (CRC). METHODS:
The genotypes of these 3 loci among 268 patients with CRC and 268 healthy controls were determined by polymerase chain reaction-restriction fragment lengthy polymorphism (PCR-RFLP). The protein levels of IL-1α, IL-8, TGF-β and TNF-α in the homogenate of CRC biopsies were measured by enzyme-linked immunosorbent assay (ELISA). RESULTS: No significant difference of the genotype frequencies of TLR4 A896G and D299G between the cases and the controls was observed. CT combined TT genotype of T399I was significantly associated with increased CRC risk. The individuals with the T allele of T399I showed a 1.843-fold increase in CRC risk as compared with the C allele. The concentrations of IL-1α and TNF-α in CRC biopsies were significantly elevated in the individuals with the genotype of T399I CT combined with TT as compared with the genotype of CC. CONCLUSION: TLR4 T399I promotes the development of CRC by modifying the expression of IL-1α and TNF-α in CRC tissues.     

Association of OPG gene single nucleotide polymorphisms with susceptibility to rheumatoid arthritis in Chinese Han population

AIM：To investigate the association of osteoprotegerin (OPG) gene single nucleotide polymorphisms (SNPs), 163A/G (rs3102735) and 245T/G (rs3134069), with susceptibility to rheumatoid arthritis (RA) in Chinese Han population. METHODS：A total of 205 patients with RA and 171 healthy control subjects were enrolled into this study. Genotyping was performed by polymerase chain reaction-based restriction fragment length polymorphism and subsequently confirmed by DNA sequencing. Odds ratio (OR) and 95% confidence intervals (CI) were calculated for the risk genotypes and alleles. RESULTS：OPG gene polymorphisms 163A/G and 245T/G were conformed to the Hardy-Weinberg equilibrium. The statistical differences in the genotypes of AA, AG and GG at 163A/G locus were found in RA and controls. The G allele was associated with an increased risk of RA, with OR of 1.219 (95％ CI: 1.066~2.339). No significant difference was observed between RA group and control group with respect to genotypic and allelic frequencies of OPG gene 245T/G (P>0.05）. CONCLUSION：The OPG gene 163A/G SNP may be associated with RA susceptibility, and G allele may be the risk factor for developing RA.     

Association between IL-6-572C/G as well as IFNAR1-168G/C and hepatitis B virus infection in populations of Dai and Han ethnicities in Yunnan Province

ATM: To explore the association between IL-6-572C/G (rs1800796) as well as interferon alpha receptor 1 (IFNAR1)-168G/C (rs2257167) and prognosis after hepatitis B virus (HBV) infection in populations of Dai and Han ethnicities in Yunnan Province. METHODS: The blood samples were collected from Dai people and Han people, each nation including 100 healthy controls and 200 infected individuals (100 spontaneous recovery individuals and 100 chronic patients). Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and DNA sequencing were used to identify the gene type. RESULTS: In Dai people, no significant difference was found between genetic polymorphism of -572C/G and prognosis after HBV infection. The differences of C and G alleles between spontaneous recovery group and chronic hepatitis B group, and healthy controls and HBV infection group were not statistically significant. Meanwhile, GG and CG genotypes were a vital protective factor for the person who developed into a chronic heptatitis B patient under the G allele dominance mode (GG+CG/CC) (P<0.05). In Han people, no statistically significance for IL-6-572C/G genotype and allele distribution in each group comparisons had been found, as well as the C allele recessive mode and C allele dominance mode. For the above 4 indicators, no statistically significant difference of IFNAR1-168C/G in Dai and Han people had been found.CONCLUSION: The GG+CG genotype of IL-6-572C/G may be a protective factor for the HBV-infected Dai people to develop into chronic hepatitis B patients. However, there is no significant association between the IFNAR1-168G/C polymorphism and prognosis after HBV infection in the 2 ethnicities.     

Association of polymorphism of Fc receptor γ chain gene at position-29 in promoter with the susceptibility to systemic lupus erythematosus in southern Chinese

AIM:To detect the association between the polymorphism of Fc receptor γ chain gene at position-29 in promoter and systemic lupus erythematosus(SLE).METHODS:The genotypes at position -29 in promoter of Fc receptor γ chain gene were determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method in 180 patients with SLE and 140 ethnically matched controls in southern China.RESULTS:The frequencies of TT genotype(33.3%) and T allele (54.4%) at position -29 in patients with SLE were significantly higher than those in controls (17.2% and 42.9%, respectively), whereas, the frequencies of GG genotype (24.4%) and G allele (45.6%) in patients with SLE were remarkably lower than those in controls (31.4% and 57.1%, respectively) (P＜0.05). The TT genotype and T allele at position -29 were not associated with lupus nephritis in SLE patients (P＞0.05).CONCLUSION:Our results indicate that the T allele at position -29 in promoter of Fc receptor gene probably contributes to the susceptibility to SLE, but does not play a role in the occurrence of lupus nephritis.     

Association of IFN-γ and IL-4 gene polymorphisms with childhood bronchial asthmatic susceptibility and the levels of plasma IFN-γ,IL-4 and IgE

AIM: To investigate the gene polymorphisms of interferon-γ(IFN-γ) and interleukin-4(IL-4) and the association with asthmatic susceptibility and the levels of plasma IFN-γ, IL-4 and IgE of asthmatic children. METHODS: 100 asthmatic children and 122 control children were enrolled the study. The genotypes of IFN-γ gene-179G/T polymorphism, IL-4 gene-33C/T and-589C/T polymorphisms were tested by PCR-RFLP.The genotype of IFN-γ gene +874A/T polymorphism was tested by AS-PCR.The CA repeat polymorphism of IFN-γ gene was detected by capillary electrophoresis technique.The levels of serum IFN-γ, IL-4 and IgE were measured by ELISA. RESULTS: 100 asthmatic children and 122 control children were all GG homozygotes at -179 locus of IFN-γ gene.-179 locus of IFN-γ gene has no mutation. The genotypes and allele frequency of IFN-γ gene +874A/T and CA repeat polymorphisms showed no significant difference between asthmatic children and the control(P>0.05). An association was revealed between IFN-γ gene +874A/T polymorphism and the level of plasma IFN-γ.The level of IFN-γ was lower in AA genotype than in AT genotype(P<0.05). The genotypes and allele frequency of IL-4 gene -33C/T and -589C/T polymorphisms showed significant difference between asthmatic children and the control(P<0.05).The levels of plasma IL-4 and IgE were higher in TT genotype at -33 locus and -589 locus than those in CT genotype, but only -33C/T polymorphism was associated with the level of plasma IL-4(P<0.05). CONCLUSION: The IFN-γ gene +874A/T and CA repeat polymorphisms were not correlated with asthmatic susceptibility, but there is significant correlation between the level of IFN-γ and +874A/T polymorphism. TT genotype of IL-4 gene -33 locus and -589 locus maybe the susceptible genotype of asthma in children, and the -33 locus polymorphism is associated with the level of IL-4.     

Correlation between DDAH2 gene polymorphism and coronary heart disease

AIM: To investigate the relationship between single nucleotide polymorphism (SNP) of dimethylarginine dimethylamino acid hydrolase (DDAH) gene and coronary heart disease (CHD) in Chinese population. METHODS: The polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and ligase detection reaction (LDR) were used to detect the genotypes of SNP rs805305 and rs2272592 in 192 controls and 165 patients with coronary heart disease (CHD). RESULTS: Both the frequency of rs805305 CG+GG or G allele and the frequency of rs2272592 GA+AA or A allele had no significant difference between CHD and control (P＞0.05). These results were independent of age, gender, hypertension, diabetes and hyperlipidemia. CONCLUSION: The rs805305 and rs2272592 polymorphism of DDAH2 gene might not be related to the coronary heart disease (CHD) in Chinese.     

Genetic polymorphisms of RTN4 gene in Chinese Guangxi population

AIM: To investigate the distribution characteristics of rs2920891A/C and rs17046647A/G polymorphisms of RTN4 gene in Guangxi population, and to compare the differences among different populations. METHODS: The genotypes of RTN4 gene at rs2920891A/C and rs17046647A/G in 323 healthy persons of Guangxi were performed by the technique of SNaPshot and DNA sequencing. The results were compared with the alleles and genotypes of other populations (HapMap-CEU, HapMap-HCB, HapMap-JPT and HapMap-YRI in HapMap). RESULTS: In Guangxi population, 3 genotypes, AA, AC and CC, and 2 alleles, A and C, were found in rs2920891A/C. The allele frequencies between male and female showed significant differences (P<0.05). The genotype and allele frequencies compared with HapMap-JPT, HapMap-CEU and HapMap-YRI had differences with statistical significance (P<0.05). Three genotypes, AA, AG and GG, and 2 alleles, A and G, were found in rs17046647A/G. The genotype and allele frequencies between male and female showed no significant differences (P>0.05), but there were significant differences of the genotype and allele frequencies as compared with HapMap-JPT, HapMap-CEU and HapMap-YRI (P<0.01).CONCLUSION: The rs2920891A/C and rs17046647A/G polymorphisms of RTN4 gene in Chinese Guangxi population are different from those in other races.     

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.     

Association analysis between two SNPs in SNCA and PARK16 genes and Parkinson disease in a Han Chinese population in Liaoning area

AIM: To investigate the genotypic frequency of rs3857059 in SNCA gene and rs16856139 in PARK16 gene for determining the potential genetic risk factors of Parkinson disease (PD) in a Han Chinese population in Liaoning area of China. METHODS: The genomic DNA from 213 PD patients and 214 matched controls was amplified in the multiplex PCR system and subsequently genotyped by digestion with endonuclease Pvu II. Genetic parameter and association studies were carried out with SPSS 13.0 and PLINK 1.07 software. RESULTS: We accurately detected all genotypes in the 2 loci with PCR-restriction fragment length polymorphism (RFLP) techniques. The gene frequency of G allele in the rs3857059 locus was higher in PD group than that in control group with statistical significance (χ²= 7.592,P<0.01, OR=0.677, 95% CI=0.517~0.888). The T allele frequency in the rs16856139 locus was lower in PD group than that in control group and statistical result revealed a significant difference (χ²=11.511, P<0.01, OR=0.390, 95% CI=0.227~0.669). CONCLUSION: The 2 SNPs investigated in SNCA and PARK16 genes are likely to play roles as common risk factors for PD disease in the Han Chinese population.     

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.     

Family-based transmission disequilibrium association study on TGFβ1 -509C/T polymorphism and IgA nephropathy

AIM: To investigate the relationship between transforming groupth factor beta 1 (TGFβ1)-509C/T polymorphism and IgA nephropathy using family-based analysis of transmission disequilibrium test and haplotype relative risk. METHODS: The genotypes of TGFβ1 -509C/T were determined by PCR-RFLP and direct sequencing. Two family-based designs, transmission disequilibrium test (TDT) and haplotype-based haplotype relative risk (HRR) were employed for the data analysis. The patients were followed up and clinical data retrieved and compared. RESULTS: ① No transmission disequilibrium was found from heterozygous parents onto patients in our 106 trios analyzed by TDT （χ2=0.559, P>0.05）. ② No increased risks of contracting the disease oweing to-509C/T polymorphism of TGFβ1 in our 130 trios analyzed by either genotype-based HRR or haplotype-based HRR （χ2=0.667, P>0.05; χ2=0.650, P>0.05, HRR=0.878）. ③ 296 cases of IgA nephropathy were tracked for nearly two years, the results showed that the CC genotype frequency was very significantly higher in patients with renal function deterioration ［χ2 (CC/others)=10.402, P<0.01, OR=2.900］. CONCLUSION: TGFβ1-509 CC genotype may be associated with progression of IgA nephropathy, but the -509C/T polymorphism is not associated with susceptibility to this disease in Chinese Han population.     

Genetic polymorphism of caspase-7 isoform β in patients with rheumatoid arthritis

AIM: To investigate the association between the rs2227309 polymorphism of cysteinyl aspartate-specific protease-7 (caspase-7) isoform β and the genetic susceptibility in rheumatoid arthritis (RA) patients in Taizhou of China. METHODS: Genotyping of rs2227309 of caspase-7 isoform β gene was performed in 204 RA patients and 203 matched healthy controls using TaqMan single nucleotide polymorphism (SNP) genotyping assays. RESULTS: The genotype frequencies of GG, AG and AA of caspase-7 polymorphism in the RA patients were 33.3%, 53.4% and 13.2%, respectively, and 33.0%, 44.3% and 22.7% in the healthy individuals,respectively. There was a significant difference in caspase-7 genotype frequencies between the RA patients and healthy controls (P<0.05). The frequency of GG+AG genotype in RA patients was higher than that in healthy controls with significant difference (P<0.05, OR=1.921, 95%CI: 1.140~3.236). The frequencies of the G allele were 60.0% and 55.2% in the RA patients and the healthy individuals,respectively. No significant difference was observed in allele frequency between the RA patients and healthy controls (P>0.05, OR=1.221, 95%CI: 0.924~1.613). CONCLUSION: The rs2227309 polymorphism of caspase-7 isoform β gene is associated with the susceptibility to rheumatoid arthritis. The high production of the non-functional variant of caspase-7 may reduce the apoptosis of rheumatoid synovial cells, indicating the mechanism of this association.     

Association of rs2162459 polymorphism in CYP7A1 gene with effectiveness of atorvastatin in northern Chinese Han population

AIM：To investigate the association of the polymorphism of rs2162459 locus in cytochrome P-450, family 7, subfamily A, polypeptide 1 (CYP7A1) gene, encoding cholesterol 7α-hydroxylase, with the effectiveness of atorvastatin in northern Chinese Han population. METHODS：Clinical data and blood samples of 200 cases of hyperlipidemia patients were collected. The variants of rs2162459 in CYP7A1 gene were detected by multiplex SNaPshot technology. Several genetic models were constructed to analyse the association of gene polymorphism with the effectiveness of atorvastatin by logistic regression method. RESULTS：The polymorphism of rs2162459 was consistent with Hardy-Weinberg equilibrium. The baseline high-density lipoprotein cholesterol (HDL-C) concentrations in three genotypes of AA, GA and GG were (136±0.94) mmol/L, (1.16±0.38) mmol/L and (1.07±0.28) mmol/L, respectively (P<0.05). There were differences in the genotypic frequency and allelic frequency between atorvastatin effective and ineffective groups (both P<005). Significant differences in regulating HDL-C level among the three genotypes of rs2162459 were found after logistic regression. The results of additive model, generalized model and dominant model, presented as OR (95% CI), were 1.74 (1.09~2.77), 2.86 (1.13~7.25) and 2.21 (1.12~4.33), respectively. CONCLUSION: The baseline HDL-C level in the carriers of GG genotype is lower than that in the carriers of the other two genotypes. The HDL-C-elevating effect of atorvastatin on GG genotype carriers is more significant than that on AA genotype carriers.     

Association of S100B polymorphisms with systemic lupus erythematosus in Guangxi population

AIM: To explore the association of rs9984765, rs2839356 and rs2186358 polymorphisms in S100B gene with the susceptibility to systemic lupus erythematosus (SLE). METHODS: SLE patients (n=313) and age-and sex-matched healthy controls (n=396) were recruited in this study. The genotypes of the 3 sites were determined by single-base extension PCR (SBE-PCR) and DNA sequencing. RESULTS: No difference between the SLE patients and controls in the genotype and allele frequencies of rs9984765 and rs2186358 was observed. However, the frequency distribution of rs2839356 C allele was significantly different in the 2 groups (P=0.040). Stratification analysis showed that the frequency of rs2839356 C allele was higher in the patients with neurologic disorder than the patients without neurologic disorder (P=0.023).CONCLUSION: S100B gene rs9984765 and rs2186358 polymorphisms may not contribute to the susceptibility of SLE in Guangxi population. The rs2839356 C allele might be correlated with the SLE patients with neurologic disorder.     

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.