EBM Research Center, Kyoto University Graduate School of Medicine, Kyoto, Japan.
J Hum Genet. 2011 Oct;56(10):716-9. doi: 10.1038/jhg.2011.86. Epub 2011 Jul 28.
Visceral fat accumulation has an important role in increasing morbidity and mortality rate by increasing the risk of developing several metabolic disorders, such as type 2 diabetes, dyslipidemia and hypertension. New genetic loci that contribute to the development of obesity have been identified by genome-wide association studies in Caucasian populations. We genotyped 1279 Japanese subjects (556 men and 723 women), who underwent computed tomography (CT) for measuring visceral fat area (VFA) and subcutaneous fat area (SFA), for the following single-nucleotide polymorphisms (SNPs): NEGR1 rs2815752, SEC16B rs10913469, TMEM18 rs6548238, ETV5 rs7647305, GNPDA2 rs10938397, BDNF rs6265 and rs925946, MTCH2 rs10838738, SH2B1 rs7498665, MAF rs1424233, and KCTD15 rs29941 and rs11084753. In the additive model, none of the SNPs were significantly associated with body mass index (BMI). The SH2B1 rs7498665 risk allele was found to be significantly associated with VFA (P=0.00047) but not with BMI or SFA. When the analysis was performed in men and women separately, no significant associations with VFA were observed (P=0.0099 in men and P=0.022 in women). None of the other SNPs were significantly associated with SFA. Our results suggest that there is a VFA-specific genetic factor and that a polymorphism in the SH2B1 gene influences the risk of visceral fat accumulation.
内脏脂肪堆积通过增加发生多种代谢紊乱的风险，如 2 型糖尿病、血脂异常和高血压，从而在增加发病率和死亡率方面起着重要作用。全基因组关联研究已经在白种人群中确定了有助于肥胖发展的新遗传位点。我们对 1279 名接受 CT 测量内脏脂肪面积 (VFA) 和皮下脂肪面积 (SFA) 的日本受试者（556 名男性和 723 名女性）进行了基因分型，用于以下单核苷酸多态性 (SNP)：NEGR1 rs2815752、SEC16B rs10913469、TMEM18 rs6548238、ETV5 rs7647305、GNPDA2 rs10938397、BDNF rs6265 和 rs925946、MTCH2 rs10838738、SH2B1 rs7498665、MAF rs1424233 和 KCTD15 rs29941 和 rs11084753。在加性模型中，没有一个 SNP 与体重指数 (BMI) 显著相关。发现 SH2B1 rs7498665 风险等位基因与 VFA 显著相关 (P=0.00047)，但与 BMI 或 SFA 无关。当分别在男性和女性中进行分析时，没有观察到与 VFA 显著相关的情况（男性 P=0.0099，女性 P=0.022）。其他 SNP 与 SFA 均无显著相关性。我们的研究结果表明存在 VFA 特异性遗传因素，并且 SH2B1 基因的多态性影响内脏脂肪堆积的风险。
