腹部脂肪相关的新基因！

在2014年1月6日的《Human Molecular Genetics》杂志上发表的一项最新研究中，美国路易斯维尔大学的研究人员，发现了与腹部脂肪相关的5个新基因，使科学家们向“治疗肥胖或肥胖相关疾病的药物疗法开发”迈出了更近的一步。

　　

　　　多余的腹部脂肪可能是一些疾病的前兆，如心血管疾病、2型糖尿病和癌症。一个人腹部脂肪的衡量，反映在腰围和臀围的比例上，据估计，约30%至60%的腰臀比（waist-to-hip ratio，WHR）是遗传所致。美国路易斯维尔大学公共卫生与信息科学学院的助理教授Kira Taylor博士及其团队，发现了与WHR增长相关的5个新基因，使科学家们向“治疗肥胖或肥胖相关疾病的药物疗法开发”迈出了更近的一步。这项研究成果发表在2014年1月6日的《Human Molecular Genetics》杂志上。
　　　该研究团队对超过57,000名欧洲血统的人进行了分析，寻找增加高WTH比例风险的基因。他们调查了被认为涉及心血管或代谢特征的2,000个基因中的50,000个以上的遗传变异。
　　　他们的这项分析，确定了与男性和女性中WHR增高有关的3个新基因，发现两个似乎只影响女性WHR的新基因。在后者这两个基因中，有一个基因SHC1，可能与已知参与肥胖、在脂肪组织中高表达的其他17个蛋白相互作用。此外，研究团队在SHC1中发现的遗传变异，与引起蛋白中一个氨基酸改变的另一个变异相关，可能会改变蛋白质的功能或表达。
　　　Taylor说：“这是第一次证明，SHC1与腹部脂肪有关。我们相信，这一发现，为药物化学（最终是个性化医学）提供了很好的机会。如果科学家们能够找到一种方式来调节此基因的表达，我们就有可能减少腹部多余脂肪的风险及其后果，例如心血管疾病。”
　　　之前已经有研究发现，缺乏SHC1蛋白的小鼠更瘦，表明这个分子通过为正常生长和发育供应过多的营养，在新陈代谢失衡和细胞过早退化中发挥作用。
　　　另外有证据表明，SHC1能够激活胰岛素受体，触发多个影响脂肪细胞生长的信号事件。（生物通：王英）

原文摘要：
Gene-centric meta-analyses for central adiposity traits in up to 57 412 individuals of European descent confirm known loci and reveal several novel associations
Abstract: Waist circumference (WC) and waist-to-hip ratio (WHR) are surrogate measures of central adiposity that are associated with adverse cardiovascular events, type 2 diabetes and cancer independent of body mass index (BMI). WC and WHR are highly heritable with multiple susceptibility loci identified to date. We assessed the association between SNPs and BMI-adjusted WC and WHR and unadjusted WC in up to 57 412 individuals of European descent from 22 cohorts collaborating with the NHLBI's Candidate Gene Association Resource (CARe) project. The study population consisted of women and men aged 20-80 years. Study participants were genotyped using the ITMAT/Broad/CARE array, which includes ∼50 000 cosmopolitan tagged SNPs across ∼2100 cardiovascular-related genes. Each trait was modeled as a function of age, study site and principal components to control for population stratification, and we conducted a fixed-effects meta-analysis. No new loci for WC were observed. For WHR analyses, three novel loci were significantly associated (P < 2.4 × 10-6). Previously unreported rs2811337-G near TMCC1 was associated with increased WHR (β ± SE, 0.048 ± 0.008, P = 7.7 × 10-9) as was rs7302703-G in HOXC10 (β = 0.044 ± 0.008, P = 2.9 × 10-7) and rs936108-C in PEMT (β = 0.035 ± 0.007, P = 1.9 × 10-6). Sex-stratified analyses revealed two additional novel signals among females only, rs12076073-A in SHC1 (β = 0.10 ± 0.02, P = 1.9 × 10-6) and rs1037575-A in ATBDB4 (β = 0.046 ± 0.01, P = 2.2 × 10-6), supporting an already established sexual dimorphism of central adiposity-related genetic variants. Functional analysis using ENCODE and eQTL databases revealed that several of these loci are in regulatory regions or regions with differential expression in adipose tissue.