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

Abstract

The predominant risk factor of metabolic syndrome is intra-abdominal fat accumulation, which is determined by waist circumference, waist-hip ratio measurements and visceral fat area (VFA); the latter can be accurately measured by performing computed tomography (CT). In addition to environmental factors, genetic factors play an important role in obesity and fat distribution. New genetic loci associated with body mass index (BMI) and adiposity have been identified by genome-wide association studies (GWASs). This study utilized CT to investigate whether single nucleotide polymorphisms (SNPs) that confer susceptibility to higher BMI are associated with VFA, subcutaneous fat area (SFA), and the ratio of VFA to SFA (V/S ratio). We measured the VFA and SFA of 1424 obese Japanese subjects (BMI ≥ 25 kg/m(2), 635 men and 789 women) who were genotyped for 13 single nucleotide polymorphisms (SNPs) reported by recent GWASs, namely, TNNI3K rs1514175, PTBP2 rs1555543, ADCY3 rs713586, IRS1 rs2943650, POC5 rs2112347, NUDT3 rs206936, LINGO2 rs10968576, STK33 rs4929949, MTIF3 rs4771122, SPRY2 rs534870, MAP2K5 rs2241423, QPCTL rs2287019, and ZC3H4 rs3810291. The G-allele of NUDT3 rs206936 was significantly associated with increased BMI (P = 5.3 × 10(-5)) and SFA (P = 0.00039) in the obese Japanese women. After adjustment with BMI, the association between rs206936 and SFA was not observed. This significant association was not observed in the men. The other SNPs analyzed were not significantly associated with BMI, VFA, SFA, or V/S ratio. Our results suggest that NUDT3 rs206936 is associated with BMI in Japanese women.

Genetic polymorphisms associated with pediatric‐onset type 2 diabetes: A family‐based transmission disequilibrium test and case‐control study

“…The genetic predisposition to obesity may contribute to the risk of T2D either by a mechanism mediated by or independently of the BMI. The SNPs LINGO2 /rs10968576, POC5 /rs2112347, and RPS10‐NUDT3 /rs206936 have been previously associated with obesity and related phenotypes (but not with T2D) . We found these variants associated with both obesity and T2D (but not independently of the obesity status).…”

Unravelling the genetic loci for growth and carcass traits in Chinese Bamaxiang pigs based on a 1.4 million SNP array

“…It was also reported that HMGA1 is a key modulator for IGF1 gene, which in turn was associated with body size in dogs (Sutter et al, ). NUDT3 involved in diadenosine polyphosphate catabolic process, and variants in this gene was reported to be associated with body mass index in humans (Kitamoto et al, ).…”

Systematic Functional Characterization of Resistance to PI3K Inhibition in Breast Cancer

“…For example, DYRK1B is a gene for which germ-line activating mutations (at codon R102C) predispose patients to early-onset diabetes and obesity, likely through enhanced adipogenesis (18). Similarly, NUDT3 has also been implicated in multiple genome-wide association studies (GWAS) to be an obesity-linked gene (19,20). It is possible that overexpression of those genes may alter the metabolic profile to render cells less sensitive to PI3K signaling.…”

“…Gain-of-function mutation in DYRK1B resulted in an inherited form of the metabolic syndrome in patients (18). NUDT3 is particularly associated with obesity in females (19,20). However, specific mechanisms through which alteration of metabolic profiles might confer resistance to PI3K inhibition in cancer remain uncharacterized.…”