Polymorphisms in NRXN3, TFAP2B, MSRA, LYPLAL1, FTO and MC4R and their effect on visceral fat area in the Japanese population

Abstract

The predominant risk factor of metabolic syndrome is intra-abdominal fat accumulation, which is determined by waist circumference and waist-hip ratio measurements and visceral fat area (VFA) that is measured by computed tomography (CT). There is evidence that waist circumference and waist-hip ratio in the Caucasian population are associated with variations in several genes, including neurexin 3 (NRXN3), transcription factor AP-2b (TFAP2B), methionine sulfoxide reductase A (MSRA), lysophospholipase-like-1 (LYPLAL1), fat mass and obesity associated (FTO) and melanocortin 4 receptor (MC4R) genes. To investigate the relationship between VFA and subcutaneous fat area (SFA) and these genes in the recruited Japanese population, we genotyped 8 single-nucleotide polymorphisms (SNPs) in these 6 genes from 1228 subjects. Multiple regression analysis revealed that gender, age, and rs1558902 and rs1421085 genotypes (additive model) in FTO were significantly associated with body mass index (BMI; P¼0.0039 and 0.0039, respectively), SFA (P¼0.0027 and 0.0023, respectively) and VFA (P¼0.045 and 0.040, respectively). However, SNPs in other genes, namely, NRXN3, TFAP2B, MSRA, LYPLAL1 and MC4R were not significantly associated with BMI, SFA or VFA. Our data suggest that some SNPs, which were identified in genome-wide studies in the Caucasians, also confer susceptibility to fat distribution in the Japanese subjects.

Association of variations in the FTO, SCG3 and MTMR9 genes with metabolic syndrome in a Japanese population

“…[15][16][17][18][19] We confirmed that some of these SNPs are also associated with obesity and visceral fat area as determined by computed tomography in the Japanese population. [20][21][22] In this study, we investigated the association between metabolic syndrome and 33 SNPs related to obesity and the obesity-related phenotype. We found that SNPs in the fat mass and obesity associated (FTO), SCG3 and MTMR9 genes are associated with metabolic syndrome.…”

Association between type 2 diabetes genetic susceptibility loci and visceral and subcutaneous fat area as determined by computed tomography

“…9,10 Among the reported loci, we have reported that the rs1558902 and rs1421085 genotypes of the fat mass-and obesityassociated gene (FTO) were significantly associated with VFA, as well as with subcutaneous fat area (SFA) and body mass index (BMI). 11 GWAS and meta-analysis of GWAS have also identified metabolic syndrome trait-associated genetic variations, including obesity, type 2 diabetes, dyslipidemia and hypertension. 12 We have previously reported that among the single-nucleotide polymorphisms (SNPs) susceptible to obesity, [13][14][15] rs7498665 in the SH2B adaptor protein 1 (SH2B1) gene was associated with VFA, 16 and that among hypertension-susceptible SNPs, 17,18 rs1004467 in the cytochrome P450, family 17, subfamily A, polypeptide 1 (CYP17A1) gene and rs11191548 in the 5¢-nucleotidase, cytosolic II (NT5C2) gene were significantly associated with both reduced VFA and SFA in women, indicating a genetic background to central obesity.…”

Computed tomography analysis of the association between the SH2B1 rs7498665 single-nucleotide polymorphism and visceral fat area

“…6,7 In a previous study, we have reported that the rs1558902 and rs1421085 genotypes of the fat mass and obesity-associated gene (FTO) were significantly associated with VFA, as well as with subcutaneous fat area (SFA) and body mass index (BMI). 8 We performed a large-scale, case-control association study and found that secretogranin III (SCG3) 9 and myotubularin-related protein 9 (MTMR9) 10 conferred susceptibility to an obese phenotype in the Japanese population. Recent progress in genome-wide association studies has increased the number of known genetic susceptibility loci for obesity.…”