Genetic variations in the CYP17A1 and NT5C2 genes are associated with a reduction in visceral and subcutaneous fat areas in Japanese women

Abstract

Visceral fat accumulation has an important role in increasing the morbidity and mortality rates, by increasing the risk of developing several metabolic disorders, such as type 2 diabetes, dyslipidemia and hypertension. New genetic loci that are associated with increased systolic and diastolic blood pressures have been identified by genome-wide association studies in Caucasian populations. This study investigates whether single nucleotide polymorphisms (SNPs) that confer susceptibility to high blood pressure are also associated with visceral fat obesity. We genotyped 1279 Japanese subjects (556 men and 723 women) who underwent computed tomography for measuring the visceral fat area (VFA) and subcutaneous fat area (SFA) at the following SNPs: FGF5 rs16998073, CACNB2 rs11014166, C10orf107 rs1530440, CYP17A1 rs1004467, NT5C2 rs11191548, PLEKHA7 rs381815, ATP2B1 rs2681472 and rs2681492, ARID3B rs6495112, CSK rs1378942, PLCD3 rs12946454, and ZNF652 rs16948048. In an additive model, risk alleles of the CYP17A1 rs1004467 and NT5C2 rs11191548 were found to be significantly associated with reduced SFA (P¼0.00011 and 0.0016, respectively). When the analysis was performed separately in men and women, significant associations of rs1004467 (additive model) and rs11191548 (recessive model) with reduced VFA (P¼0.0018 and 0.0022, respectively) and SFA (P¼0.00039 and 0.00059, respectively) were observed in women, but not in men. Our results suggest that polymorphisms in the CYP17A1 and NT5C2 genes influence a reduction in both visceral and subcutaneous fat mass in Japanese women.

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

“…A recent report also indicated that rs4846567 was strongly associated with the V/S ratio in women (p = 0.0004), but not men (p = 0.05) 14) . We have recently reported that 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 reductions in both VFA and SFA in women, but not in men 21) . Our studies and previous reports highlight the need for a better understanding of the underlying molecular mechanisms in the sex differences in the regulation of the distribution of body fat.…”

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

“…16,19 These patients agreed to undergo CT testing (in the supine position) to determine the VFA and SFA values at the umbilical level (L4-L5). Both VFA and SFA values were calculated using the FatScan software program (N2system, Osaka, Japan).…”

“…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. 19 Visceral fat obesity is also a risk factor for the development of type 2 diabetes. Several studies have investigated the association of type 2 diabetes loci from GWAS with body fat and BMI.…”

<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.…”

“…ADIPOQ polymorphisms are associated with insulin resistance in Japanese women Aya Kitamoto 1) , Takuya Kitamoto 1) , Rina So 2) , Tomoaki Matsuo 2) , Yoshio Nakata 2) , Hideyuki Hyogo 3) , Hidenori Ochi 3) , Takahiro Nakamura 4) , Seika Kamohara 5) , Nobuyuki Miyatake 6) , Kazuaki Kotani 7) , Ikuo Mineo 8) , Jun Wada 9) , Yuji Ogawa 10) , Masato Yoneda 10) , Atsushi Nakajima 10) , Tohru Funahashi 11) , Shigeru Miyazaki 12) , Katsuto Tokunaga 13) , Hiroaki Masuzaki 14) , Takato Ueno 15) , Kazuaki Chayama 3) , Kazuyuki Hamaguchi 16) , Kentaro Yamada 17) , Toshiaki Hanafusa 18) , Shinichi Oikawa 19) , Toshiie Sakata 20) , Kiyoji Tanaka 2) , Yuji Matsuzawa 7) and Kikuko Hotta 1)…”