Replication Study of 15 Recently Published Loci for Body Fat Distribution in the Japanese Population
Replication Study of 15 Recently Published Loci for Body Fat Distribution in the Japanese Population
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DOI：
10.5551/jat.14589
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发表时间：
2013-01-01
影响因子：
4.4
通讯作者：
Sekine, Akihiro
中科院分区：
文献类型：
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作者：
Hotta, Kikuko;Kitamoto, Aya;Sekine, Akihiro
目的：内脏脂肪蓄积通过增加发生代谢紊乱如2型糖尿病、血脂异常和高血压的风险，在发病率和死亡率中起着不可或缺的作用。最近，在欧洲血统人群中进行的全基因组关联研究发现了与脂肪分布相关的新的遗传位点，这些基因位点通过腰臀比和计算机断层扫描（CT）测量。本研究使用CT来调查在日本人群中赋予脂肪分布易感性的单核苷酸多态性（SNPs）是否与内脏脂肪面积（VFA）和皮下脂肪面积（SFA）相关。我们测量了1424名日本肥胖受试者的VFA和SFA在15个SNP位点进行基因分型，即TBX 15 rs 984222、DNM 3 rs 1011731、LYPLAL 1 rs 4846567、GRB 14 rs 10195252、NISCH rs6784615、ADAMTS9 rs6795735、CPEB 4 rs6861681、LY86 rs1294421、VEGFA rs6905288、RSPO3 rs9491696、NFE 2L3 rs1055144、ITPR 2 rs718314、HOXC 13 rs1443512、ZNRF 3 rs4823006和THNSL 2 rs1659258。LYPLAL 1 rs 4846567的G等位基因与VFA与SFA的比率增加（V/S比率; p=0.0020）呈临界相关。LYPLAL 1 rs 4846567对女性V/S比的影响（p=0.0078）强于男性（p=0.12）;然而，在多重比较的Bonferroni校正后，两个结果都不显著。NISCH rs6784615名义上与VFA（p=0.040）和V/S比（p=0.020）增加相关。其他SNPs分析没有显着相关的体重指数（BMI），VFA，或SFA.Conclusion：我们的研究结果表明，LYPLAL 1 rs 4846567和NISCH rs6784615可能会影响脂肪分布在日本人口。
Aim: Visceral fat accumulation plays an integral role in morbidity and mortality rates by increasing the risk of developing metabolic disorders such as type 2 diabetes, dyslipidemia, and hypertension. New genetic loci associated with fat distribution, measured by waist-hip ratios and computed tomography (CT), have recently been identified by genome-wide association studies in European-descent populations. This study used CT to investigate whether single nucleotide polymorphisms (SNPs) that confer susceptibility to fat distribution are associated with visceral fat area (VFA) and subcutaneous fat area (SFA) in the Japanese population.Methods: We measured the VFAs and SFAs of 1424 obese Japanese subjects (BMI >= 25 kg/m(2), 635 men and 789 women) that were genotyped at 15 SNPs, namely, TBX15 rs984222, DNM3 rs1011731, LYPLAL1 rs4846567, GRB14 rs10195252, NISCH rs6784615, ADAMTS9 rs6795735, CPEB4 rs6861681, LY86 rs1294421, VEGFA rs6905288, RSPO3 rs9491696, NFE2L3 rs1055144, ITPR2 rs718314, HOXC13 rs1443512, ZNRF3 rs4823006 and THNSL2 rs1659258.Results: The G-allele of LYPLAL1 rs4846567 was borderline associated with an increased ratio of VFA to SFA (V/S ratio; p=0.0020). LYPLAL1 rs4846567 had a stronger effect on the V/S ratio in women (p=0.0078) than in men (p=0.12); however, neither result was significant after Bonferroni correction for multiple comparisons. NISCH rs6784615 was nominally associated with increased VFA (p=0.040) and V/S ratio (p=0.020). The other SNPs analyzed were not significantly associated with body mass index (BMI), VFA, or SFA.Conclusion: Our results suggest that LYPLAL1 rs4846567 and NISCH rs6784615 may influence fat distribution in the Japanese population.