Comment on "A common genetic variant is associated with adult and childhood obesity"

Contrary to the findings of Herbert et al. (Reports, 14 April 2006, p. 279), homozygous carriers of the C allele of the rs7566605 variant near the INSIG2 gene did not exhibit a significantly increased risk for obesity in a large population-based cross-sectional German study. A subgroup analysis, however, revealed that this allele significantly increased the risk for obesity in already overweight individuals.     

异常型窄脊江豚的体型参数及肝脏组织学分析

对2016年2月在上海崇明岛水域发现的1头超重雌性窄脊江豚东亚亚种遗骸作了年龄鉴定,并将体型参数、腹壁脂肪层及肝脏组织等与同龄的正常个体作了比较。分析显示,该江豚为2龄,体长115.0 cm、体质量29.9 kg、最大体围86.2 cm、体质指数(BMI)22.6 kg/m~2、体围指数(BGI)75.0%和腹部脂肪层厚度3.5~4.3 cm,均明显大于同一水域的其他8头同龄个体。参照人类体质指数(BMI)等判断肥胖的方法和标准,发现该江豚已达到肥胖程度。实验样本的肝脏质量占体质量3.3%,肝脂肪含量高达9.27%±1.67%,脂肪占肝脏切面的体积也达40.81%±2.09%,分别是正常或对照样本的1.4、2.63和1.75倍。肉眼观察发现,实验江豚的肝脏表面凹凸粗糙,内部出现了短肌纤维束脂肪样的病变。石蜡切片显示,低倍镜下有大量的嗜酸性粒细胞浸润;高倍镜下轻度病变部位的肝细胞已发生了明显的空泡状病变,高度病变部位仅可见完全坏死的肝细胞。研究表明,该肥胖江豚已发生了严重的脂肪肝病变,并与体型参数、腹壁脂肪厚度存在着相关性,这些发现对江豚的人工驯养和迁地保护具有积极的指导意义。     

FTO——肥胖相关新基因*

 FTO基因是最近发现的一个与肥胖相关的基因,广泛地分布于生物界中,在动物多种组织中均有表达,而在下丘脑中表达最高。FTO基因的表达产物是一种核酸修复酶,能作用于下丘脑弓状核,调节食欲和能量代谢。基因组关联分析发现：FTO基因内有许多单核苷酸多态性位点,这些单核苷酸多态性位点与肥胖和胰岛素敏感性有关,FTO基因的变异增加肥胖和2-型糖尿病的风险。FTO基因是肥胖和2型糖尿病的候选新基因。     

A common genetic variant is associated with adult and childhood obesity

Obesity is a heritable trait and a risk factor for many common diseases such as type 2 diabetes, heart disease, and hypertension. We used a dense whole-genome scan of DNA samples from the Framingham Heart Study participants to identify a common genetic variant near the INSIG2 gene associated with obesity. We have replicated the finding in four separate samples composed of individuals of Western European ancestry, African Americans, and children. The obesity-predisposing genotype is present in 10% of individuals. Our study suggests that common genetic polymorphisms are important determinants of obesity.     

A common variant on chromosome 9p21 affects the risk of myocardial infarction

The global endemic of cardiovascular diseases calls for improved risk assessment and treatment. Here, we describe an association between myocardial infarction (MI) and a common sequence variant on chromosome 9p21. This study included a total of 4587 cases and 12,767 controls. The identified variant, adjacent to the tumor suppressor genes CDKN2A and CDKN2B, was associated with the disease with high significance. Approximately 21% of individuals in the population are homozygous for this variant, and their estimated risk of suffering myocardial infarction is 1.64 times as great as that of noncarriers. The corresponding risk is 2.02 times as great for early-onset cases. The population attributable risk is 21% for MI in general and 31% for early-onset cases.     

牛AGPAT6基因遗传特征与奶牛产奶性能相关性研究

 【目的】研究牛AGPAT6基因的遗传多态及其对奶牛产奶性能的影响，以期找到可用的分子标记，为奶牛的分子育种提供依据。【方法】利用PCR-RFLPs方法分析了3个不同品系荷斯坦牛AGPAT6基因第3内含子PstI等7种酶切多态性，分析了2个多态位点对3个品系奶牛产奶量、乳脂率、乳蛋白率及乳中体细胞评分的影响。【结果】牛AGPAT6基因第3内含子的PstI-RFLPs和BanI-RFLPs普遍存在于中国荷斯坦、澳洲荷斯坦和加拿大荷斯坦3个试验群体。PstI-RFLPs和BanI-RFLPs与荷斯坦牛的乳脂率呈显著的相关(P <0.05)；PstI-RFLPs与荷斯坦牛的体细胞评分呈显著的相关(P <0.05)；BanI-RFLPs与荷斯坦牛的305 d产奶成年当量呈显著的相关（P < 0.05)。【结论】牛AGPAT6基因第3内含子的PstI酶切位点突变，等位基因B为乳脂率和体细胞评分的优势等位基因。BanI酶切位点突变，等位基因D为乳脂率的优势等位基因；等位基因C为产奶量的优势等位基因。     

Complement factor H polymorphism in age-related macular degeneration

Age-related macular degeneration (AMD) is a major cause of blindness in the elderly. We report a genome-wide screen of 96 cases and 50 controls for polymorphisms associated with AMD. Among 116,204 single-nucleotide polymorphisms genotyped, an intronic and common variant in the complement factor H gene (CFH) is strongly associated with AMD (nominal P value <10(-7)). In individuals homozygous for the risk allele, the likelihood of AMD is increased by a factor of 7.4 (95% confidence interval 2.9 to 19). Resequencing revealed a polymorphism in linkage disequilibrium with the risk allele representing a tyrosine-histidine change at amino acid 402. This polymorphism is in a region of CFH that binds heparin and C-reactive protein. The CFH gene is located on chromosome 1 in a region repeatedly linked to AMD in family-based studies.     

牛DGAT1基因K232A取代对3个品种奶牛群体部分经济性状的影响

利用单链构向多态性方法检测了牛DGAT1基因第8外元AA→GC碱基突变,分析了该突变在三河牛、中国荷斯坦奶牛和中国西门塔尔奶牛中等位基因的分布频率,以及该突变对这3个品种奶牛群体产奶量、乳脂和乳蛋白含量的影响,并分析了该突变在鲁西牛、晋南牛、秦川牛和南阳牛中等位基因分布频率。结果表明,编码赖氨酸的等位基因K在三河牛、中国荷斯坦牛和中国西门塔尔牛中的分布频率分别为0.17,0.33和0.04,在鲁西牛、晋南牛、秦川牛和南阳牛4个中国地方品种中的分布频率分别为0.72,0.39,0.46和0.83;K232A取代与三河牛的平均乳脂率相关(P=0.017),KK和KA基因型个体的平均乳脂率分别较AA基因型个体高0.80%和0.41%。     

光周期和高脂食物对雌性高山姬鼠能量代谢和产热的影响

为了研究光周期和高脂食物对小型哺乳动物能量代谢和产热的影响,将成年雌性高山姬鼠分别驯化于长光照低脂、高脂食物和短光照低脂、高脂食物条件下,7周后测定动物的体重、能量摄入、产热、身体组成、血清瘦素浓度以及体脂含量等参数。结果发现:1)短光照抑制体重增长,降低血清瘦素浓度,增加非颤抖性产热;2)高脂食物使摄入能减少,消化率和体脂含量提高,但未显著影响体重、基础代谢率、非颤抖性产热和血清瘦素浓度;3)血清瘦素浓度与摄入能不相关,但与体脂重量正相关。结果暗示:短光照下瘦素作用敏感性增加和产热能力增强,可能介导了抵抗高脂食物诱导的肥胖。在野外条件下,高山姬鼠能通过能量代谢和产热的适应性调节避免体重的过度增长,有利于降低捕食风险,增强生存能力。     

Integration of association and computational methods reveals functional variants of LEPR gene for abdominal fat content in chickens

Leptin receptor(LEPR) plays a vital role in obesity in humans and animals. The objective of this study is to assess LEPR functional variants for chicken adipose deposition by integration of association and in-silico analysis using a unique chicken population, the Northeast Agricultural University broiler lines divergently selected for abdominal fat content(NEAUHLF). Five online bioinformatics tools were used to predict the functionality of the single nucleotide polymorphisms(SNPs) in coding region. Further, the possible structure–function relationship of high confidence SNPs was determined by bioinformatics analyses, including the conservation and stability analysis based on amino acid residues, prediction of protein ligand-binding sites, and the superposition of protein tertiary structure. Meanwhile, we analyzed the association between abdominal fat traits and 20 polymorphisms of chicken LEPR gene. The integrated results showed that rs731962924(N867 I) and rs13684622(C1002 R) could lead to striking changes in the structure and function of proteins, of which rs13684622(C1002 R) was significantly associated with abdominal fat weight(AFW, P=0.0413) and abdominal fat percentage(AFP, P=0.0260) in chickens. Therefore, we are of the opinion that rs13684622(C1002 R) may be an essential functional SNP affecting chicken abdominal fat deposition, and potentially applied to improvement of broiler abdominal fat in molecular marker-assisted selection(MAS) program. Additionally, the coupling of association with computer electronic predictive analysis provides a new avenue to identify important molecular markers for breeders.     

恰恰舞对单纯性肥胖女大学生体能影响的实证研究

通过整群抽样、实验干预、统计分析等方法，研究以恰恰舞为主的综合干预措施对单纯性肥胖女大 学生体能的影响效果。结果发现：干预后受试者身体形态、身体机能、身体素质指标中，除身高、握力干 预前、后差异不具显著性外，体重、BMI、腰围、WHR、体脂肪率、肺活量(mL)、台阶评定指数、仰卧起坐 （个）、立定跳远（cm）指标，干预前、后差异均具显著性。结果表明：以恰恰舞为主的综合干预措施对 改善单纯性肥胖女大学生的体能起到了积极的作用。     

不同冠型鸡H-FABP基因单核苷酸多态性与脂肪性状的关联分析

以H-FABP为候选基因设计8对引物,采用PCR-SSCP技术对单冠、玫瑰冠、豆冠、胡桃冠4种不同冠型鸡H-FABP基因进行多态性分析,探讨H-FABP基因各位点对不同冠型鸡腹脂质量、IMF性状的影响。结果表明,8对H-FABP基因引物中有6对具有SNP多态,而且6对引物均仅检测到A和B两个等位基因,4种冠型鸡的B基因在H-89、H-110、H-775位点中为优势基因,A基因在H-274、H-1910位点中为优势基因,4种冠型鸡的基因杂合度、多态信息含量均在0.5以下,H-FABP基因对单冠鸡、玫瑰冠鸡和胡桃冠鸡3种冠鸡的腹脂质量、IMF有极显著或显著影响,可作为这3种冠型鸡腹脂质量和IMF选育的候选基因。     

Variant of SCN5A sodium channel implicated in risk of cardiac arrhythmia

Every year, approximately 450,000 individuals in the United States die suddenly of cardiac arrhythmia. We identified a variant of the cardiac sodium channel gene SCN5A that is associated with arrhythmia in African Americans (P = 0.000028) and linked with arrhythmia risk in an African-American family (P = 0.005). In transfected cells, the variant allele (Y1102) accelerated channel activation, increasing the likelihood of abnormal cardiac repolarization and arrhythmia. About 13.2% of African Americans carry the Y1102 allele. Because Y1102 has a subtle effect on risk, most carriers will never have an arrhythmia. However, Y1102 may be a useful molecular marker for the prediction of arrhythmia susceptibility in the context of additional acquired risk factors such as the use of certain medications.     

A variant of the HTRA1 gene increases susceptibility to age-related macular degeneration

Age-related macular degeneration (AMD) is the most common cause of irreversible vision loss in the developed world and has a strong genetic predisposition. A locus at human chromosome 10q26 affects the risk of AMD, but the precise gene(s) have not been identified. We genotyped 581 AMD cases and 309 normal controls in a Caucasian cohort in Utah. We demonstrate that a single-nucleotide polymorphism, rs11200638, in the promoter region of HTRA1 is the most likely causal variant for AMD at 10q26 and is estimated to confer a population attributable risk of 49.3%. The HTRA1 gene encodes a secreted serine protease. Preliminary analysis of lymphocytes and retinal pigment epithelium from four AMD patients revealed that the risk allele was associated with elevated expression levels of HTRA1 mRNA and protein. We also found that drusen in the eyes of AMD patients were strongly immunolabeled with HTRA1 antibody. Together, these findings support a key role for HTRA1 in AMD susceptibility and identify a potential new pathway for AMD pathogenesis.     

Genetic variant BDNF (Val66Met) polymorphism alters anxiety-related behavior

A common single-nucleotide polymorphism in the brain-derived neurotrophic factor (BDNF) gene, a methionine (Met) substitution for valine (Val) at codon 66 (Val66Met), is associated with alterations in brain anatomy and memory, but its relevance to clinical disorders is unclear. We generated a variant BDNF mouse (BDNF(Met/Met)) that reproduces the phenotypic hallmarks in humans with the variant allele. BDNF(Met) was expressed in brain at normal levels, but its secretion from neurons was defective. When placed in stressful settings, BDNF(Met/Met) mice exhibited increased anxiety-related behaviors that were not normalized by the antidepressant, fluoxetine. A variant BDNF may thus play a key role in genetic predispositions to anxiety and depressive disorders.     

Do Improvements of living standards lead to growth of obesity? Evidence from Chinese adults

This study estimates the impacts of income on body mass indices(BMIs) of male and female adults from both urban and rural areas in China under the neoclassic theory of obesity, using China Health and Nutrition Survey data during 1991–2011.Results of this study show that incomes has a significant inverted U-shaped impact on weight for both urban and rural males while having a negative effect on weight for urban females and positive effect on BMI for rural female, suggesting that further income growth is expected to lead to continuing growth of obesity for both urban and rural male adults as well as for rural female adults. Moreover, the strenuousness of physical activity, which is represented by types of jobs, significantly reduced the BMI for all adults except for urban females, implying that a decrease in the strenuousness of physical activity stemming from economic development and technological changes is an important factor leading to the growth of obesity for all adults and rural female adults.     

Extended longevity in mice lacking the insulin receptor in adipose tissue

Caloric restriction has been shown to increase longevity in organisms ranging from yeast to mammals. In some organisms, this has been associated with a decreased fat mass and alterations in insulin/insulin-like growth factor 1 (IGF-1) pathways. To further explore these associations with enhanced longevity, we studied mice with a fat-specific insulin receptor knockout (FIRKO). These animals have reduced fat mass and are protected against age-related obesity and its subsequent metabolic abnormalities, although their food intake is normal. Both male and female FIRKO mice were found to have an increase in mean life-span of approximately 134 days (18%), with parallel increases in median and maximum life-spans. Thus, a reduction of fat mass without caloric restriction can be associated with increased longevity in mice, possibly through effects on insulin signaling.     

桑椹醋减肥与抗疲劳作用的动物试验

为了了解桑椹醋的减肥与抗疲劳作用,利用高脂肪营养饲料建立小鼠营养性肥胖模型,设立普通对照组(饲喂基础饲料)、营养对照组(饲喂营养饲料)和试验组(饲喂营养饲料和桑椹醋),对桑椹醋的减肥降脂功能进行了研究;并通过游泳耐疲劳试验,设立试验组(饲喂基础饲料和桑椹醋)和对照组(饲喂基础饲料),对桑椹醋的抗疲劳作用进行了测定分析。结果表明,在30 d小鼠喂养试验中,营养对照组、普通对照组和试验组小鼠生长发育均正常,与普通对照组相比,营养对照组小鼠质量显著(P<0.05)增加,小鼠生殖器周围脂肪总质量、脂肪系数、胆固醇和甘油三酯等指标均显著(P<0.05)提高,表明营养性肥胖模型建模可行;饲喂桑椹醋的试验组小鼠质量增长速度明显低于对照组,胆固醇和甘油三酯含量也有明显降低,并且游泳存活时间极显著(P<0.01)长于对照组,说明桑椹醋有一定的减肥功能和抗疲劳作用。     

章鱼胺对营养性肥胖小鼠减肥作用的研究

采用高脂饲料建立小鼠肥胖模型,以小鼠体重、Lee's指数、脂肪湿重、脂肪系数、血清总胆固醇(TC)、甘油三脂(TC)及高密度脂蛋白(HDL-C)等指标的变化,研究章鱼胺对小鼠的减肥作用.结果表明,肥胖对照组小鼠较普通对照组小鼠的体重、脂肪湿重、脂肪系数、血清总胆固醇(TC)、甘油三脂(TG)及高密度脂蛋白(HDL-C)含量均显著增加(P<0.05),表明营养肥胖模型构建成功;章鱼胺各剂量组及阳性对照组中小鼠的体重、脂肪湿重、脂肪系数、血清总胆固醇(TC)与模型组存在显著性差异(P<0.05),其中Lee's指数和甘油三脂(TG)的中、高剂量组与模型组存在显著性差异(P<0.05);章鱼胺对营养性肥胖小鼠有一定的减肥降脂作用.     

多囊卵巢综合征临床分型与中医证型的相关性分析

目的 探讨多囊卵巢综合征（polycystic ovarian syndrome,PCOS）患者不同临床分型与中医证型的相关性。方法 将132例多囊卵巢综合征患者根据睾酮（T）水平及体质量指数（BMI）,分为高雄组、非高雄组及肥型、瘦型、正常型;根据中医四诊分类,将PCOS患者辨证分型,主要分为肾虚肝郁证、肾虚血瘀证、肾虚痰阻证、肝郁血瘀证、脾虚痰湿证、肝经湿热证、痰瘀互结证七大证。观察不同的临床分型与中医证型的规律。结果 132例PCOS患者中,肾虚肝郁证45.5%,肾虚血瘀证11.3%,肾虚痰阻证1.5%,肝郁血瘀证16.7%,脾虚痰湿证0.8%,肝经湿热证9.1%,痰瘀互结证15.1%;肥型18.9%,瘦型18.9%,正常型62.2%。BMI从低到高的证型依次为肾虚肝郁证、肝郁血瘀证、肝经湿热证、肾虚血瘀证、肾虚痰阻证、脾虚痰湿证、痰瘀互结证。T水平从低到高依次为肥型、正常型、瘦型。不同中医证型、体型、雄激素水平无明显差异（P>0.05）,组间无统计学意义。结论 肾虚肝郁证临床较为多见,PCOS病理因素主要与虚、郁、瘀、痰相关。肝郁者的BMI偏低,形态多瘦,而痰湿者的BMI较高,形体多肥。瘦型PCOS患者T水平较肥型高。不同中医证型分类与T水平无关。