Sexual Dimorphism of a Genetic Risk Score for Obesity and Related Traits among Chinese Patients with Type 2 Diabetes

Abstract

Background: Obesity is more prevalent in men than in women in China, especially within the middle-aged population. Objectives: The present study aims to determine the contribution of sexual dimorphisms to obesity and related traits in terms of the mechanisms involving the obesity-related genetic variants among patients of Chinese Han ancestry with type 2 diabetes. Method: In the Chinese National Diabetes and Metabolic Disorders Study, 2,555 out of 4,036 patients with type 2 diabetes were treatment naive, including 1,142 men and 1,413 women. Single-nucleotide polymorphisms (SNP) from 18 genomic loci previously found to be associated with obesity-related traits were successfully genotyped, and a genetic risk score (GRS) was constructed by summing the risk alleles for obesity. Results: Single SNP analysis showed that genetic variants in SLC30A10, TMEM18, GNPDA2, PRL, TFAP2B, BDNF, MTCH2, FTO, and MC4R were nominally associated with waist circumference (WC), BMI, and risk for abdominal or general obesity in the untreated patients with type 2 diabetes, as well as in the total group of patients with type 2 diabetes (untreated and treated) (p < 0.05). Interactions between sex and SNP in PRL, MTCH2,and FTO were detected (p < 0.05). In the untreated patients with diabetes, the GRS was nominally associated with WC (β = 0.0032, SE = 0.0011; p = 0.003), BMI (β = 0.0030, SE = 0.0013; p = 0.027), and increased risk for abdominal (OR = 1.08; 95% CI 1.02–1.13; p = 0.004) or general obesity (OR = 1.07; 95% CI 1.02–1.13; p = 0.011) in men but not in women. GRS-sex interactions were detected in the determinant of WC (p = 0.019) and abdominal obesity (p = 0.016). Among patients aged 30–60 years, GRS was found to be significantly associated with WC (β = 0.0050, SE = 0.0016; p = 0.002) and abdominal obesity (OR = 1.10; 95% CI 1.04–1.17; p = 0.001) and nominally associated with BMI (β = 0.0057, SE = 0.0020; p = 0.005) and general obesity (OR = 1.07; 95% CI 1.01–1.14; p = 0.027) in men, whereas in women none of the associations were detected. GRS-sex interactions were present in the determinant of WC (p = 0.015), BMI (p = 0.032), and abdominal obesity (p = 0.012). Among patients aged 60 years or older, neither an association of GRS with obesity-related traits nor GRS-sex interactions were detected. Conclusions: Genetic factors contribute to obesity-related traits in a sex-dependent pattern among middle-aged Chinese, and men tend to be more susceptible to the genetic risk of obesity.

The Effect Sizes of PPARγ rs1801282, FTO rs9939609, and MC4R rs2229616 Variants on Type 2 Diabetes Mellitus Risk among the Western Saudi Population: A Cross-Sectional Prospective Study

“…Clearly, the frequency of the C allele is higher in the T2DM group (0.99) than in the control group (0.88). We found a strong association of MC4R rs2229616 variant with T2DM risk similar to the results from a study of patients of Chinese Han ancestry with T2DM [53]. No study on this MC4R SNP had been conducted on T2DM patients in the Arab populations.…”

Unique genetic variants of lean nonalcoholic fatty liver disease: a retrospective cohort study

“…Based on genome-wide association analysis data, genetic variants in FTO and TFAP2B , previously known as obesity susceptibility loci, impinge independently on the risk of metabolic syndrome [ 31 ]. Studies from Asia have revealed that genetic predisposition to the FTO and TFAP2B genes contributed to a sex-dependent pattern of obesity-related traits and remarkable accumulation of abdominal fat [ 32 , 33 ]. The transcription factor TFAP2B is involved in regulating adipocyte metabolism by stimulating glucose uptake and lipid accumulation while decreasing insulin sensitivity [ 34 ].…”

Sexual Dimorphism and Sex-2D : 4D Interactions on Fasting Lipid Variables in an Adult Ghanaian Population

“…One possible reason for the lack of significant association between 2D : 4D and adult circulating testosterone may be that Leydig cells (responsible for testosterone production in There is an association between estrogen levels and fasting lipid parameters in adults according to previous studies. Premenopausal women are said to have better lipid homeostasis with a less proatherogenic lipid profile than men although there are ethnic, genetic, and environmental variabilities [35][36][37][38]. Although the sex difference is not clearly understood, HDL-C tends to be higher while LDL-C, VLDL-C, and triglycerides levels are lower in premenopausal women than in age-matched men and this has been attributed to the activities of estrogen [2].…”