Replication Study of 15 Recently Published Loci for Body Fat Distribution in the Japanese Population

Abstract

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.

The genetics of fat distribution

“…While confirming six of the 14 loci described above for WHR (TBX15-WARS2, GRB14, ADAMTS9, LY86, RSPO3, ITPR2-SSPN), two novel regions have been shown to associate significantly with WC and WHR (LHX2 and RREB1, respectively; both adjusted for BMI) in individuals of African ancestry [81]. Furthermore, recent analyses of the 14 WHR loci confirmed the potential role in FD for LYPLAL1 and NISCH in a Japanese population [82].…”

“…Although most of the previous GWAS were conducted in cohorts of European ancestry, recent studies have replicated the previously identified associations in various ethnic populations [81,82]. While confirming six of the 14 loci described above for WHR (TBX15-WARS2, GRB14, ADAMTS9, LY86, RSPO3, ITPR2-SSPN), two novel regions have been shown to associate significantly with WC and WHR (LHX2 and RREB1, respectively; both adjusted for BMI) in individuals of African ancestry [81].…”

<i>NUDT3</i> rs206936 is associated with body mass index in obese Japanese women

“…We have recently reported that SNPs in the CYP17A1 and NT5C2 genes were significantly associated with both reduced VFA and SFA in women, but not in men [33]. In addition, LYPLAL1 rs4846567 has a stronger effect on the V/S ratio in women than in men [13,16]. Therefore, some of the genetic variants may contribute the sex-specific genetic variances in fat distribution, possibly through sex steroids on transcription.…”

“…Very recently, 3 genetic loci associated with VFA and subcutaneous fat area (SFA) determined using CT were identified by GWASs [13]. We have examined the reported loci, and determined that single nucleotide polymorphisms (SNPs) in the fat mass-and obesity-associated (FTO) gene were significantly linked to SFA and that lysophospholipase-like protein 1 (LYPLAL1) rs4846567 is associated with the ratio of VFA to SFA (V/S ratio) in the Japanese population [14][15][16].…”

<i>ADIPOQ</i> polymorphisms are associated with insulin resistance in Japanese women

“…Visceral fat is evaluated by waist circumference, waist-hip ratio, bioelectrical impedance, or more precisely, measurement of visceral fat area (VFA) using computed tomography (CT) [1,15]. Numerous studies have shown that VFA is influenced by genetic loci [16][17][18][19][20][21]. However, despite the observation that ADIPOQ is a promising candidate gene for visceral fat accumulation [22,23], few studies have reported a link between ADIPOQ polymorphisms and VFA.…”