Association of four insulin resistance genes with type 2 diabetes mellitus and hypertension in the Chinese Han population

Abstract

Insulin resistance plays an important role in the development of type 2 diabetes mellitus (T2DM) and hypertension. The purpose of the present study was to evaluate the association between four insulin resistance genes (ADIPOQ, LEPR, RETN, and TRIB3) and both T2DM and hypertension. A total of 768 Han Chinese subjects were recruited into this study, including 188 cases who had T2DM alone, 223 cases who had hypertension alone, 181 cases with both T2DM and hypertension, and 176 control subjects with neither T2DM nor hypertension. Twenty-three tag SNPs in four insulin resistance genes were genotyped and analyzed for association with T2DM and hypertension. One intron SNP (rs13306519) in LEPR and one 3′UTR SNP (rs1063537) in ADIPOQ demonstrated a significant association with T2DM (P = 0.024 and 0.014 respectively). Another intron SNP (rs12037879) in LEPR and a promoter region SNP (rs266729) in ADIPOQ were significantly associated with hypertension (P = 0.041 and 0.042, respectively). These associations survived the permutation test (P = 0.023, 0.018, 0.026, and 0.035, respectively). These associations were still found to be significant in the additive model after adjusting for potential confounding factors including age, sex, BMI, HDL, LDL, total cholesterol, and triglyceride levels (P = 0.024, 0.016, 0.04, and 0.043, respectively). No other gene variants were found to be significantly associated with T2DM or hypertension (P > 0.05). None of the studied gene variants were found to be significantly associated with T2DM+ hypertension (P > 0.05). A significant interaction was observed between two SNPs rs13306519 in LEPR and rs266729 in ADIPOQ for T2DM (P_int = 0.012, OR_int = 2.67) and hypertension (P_int = 0.0041, OR_int = 2.23). These findings suggest that variants in ADIPOQ and LEPR are risk factors for T2DM and hypertension in the Chinese population and that variants in RETN and TRIB3 are not major risk factors for these diseases.

c.+62G>A and g.-420C>G RETN Polymorphisms and the Risk of Developing Type 2 Diabetes and Obesity: Original Research on a Mexican Population and Meta-analysis

“…In our population, however, there were no differences in either genotype distribution or allelic frequencies for both polymorphisms examined between the Control group and the obesity or the T2D groups; therefore, no associations were found in any of the genetic models. These results were in accordance with previous reports for Asians, Northern Americans, and Europe [21,23,24,36,37,[39][40][41][42][43]45,46]. However, two studies, conducted in Asians [8] and Africans [9] population have shown an increased risk of developing T2D related to the g.-420C>G mutation.…”

“…Five studies were not written in English or Spanish, six lacked sufficient information, seven were not case-control studies, two were duplicate studies, three considered different BMI cutoffs for obesity, and one focused on children and were therefore excluded (Figure 1). From the remaining twenty-eight studies, eighteen focused on the g.-420C>G polymorphism [8,9,19,21,[23][24][25][26][35][36][37][38][39][40][41][42][43][44] and four on the c.+62A>G polymorphism [22,25,45,46]. Our current study was also considered for the meta-analysis.…”

KCNQ1 variants associate with hypertension in type 2 diabetes and affect smooth muscle contractility in vitro

“…BMI and WHR have been associated with hypertension, DM, and cardiovascular diseases, and act as risk factors for metabolic syndromes (Fasanmade et al, ; Jiang, Liu, Fang, Wang, & Li, ; Marcadenti et al, ; Zanella, Kohlmann, & Ribeiro, ). Previously, Jiang et al () reported that factors such as age, sex, BMI, levels of high density lipoprotein (HDL), low density lipoprotein (LDL), total cholesterol, and TG are associated with hypertension in patients with T2DM. Fasanmade et al () also reported that significantly higher age, mean BMI, waist circumference, and WHR were seen in patients with T2DM along with hypertension.…”

Untitled

“…ANOVA showed influence of Gln allele of rs1137101 polymorphism of LEPR gene (Table 3) Listed changes are traditionally linked with obesity in patients with DM2 [8,9] and presented in the table 3 according to decrease of influence degree of alleles of rs1137101 polymorphism of LEPR gene: increase of BMI > hyperleptinemia > dyslipidemia (increase of triglycerides and decrease of protective HDL), which were on the background of increase of insulin resistance.…”

“…Numeral data [8][9][10] shows that rs1137101 polymorphism of LEPR gene leads to disorder of structure and function of leptin receptor and blocks its expression with alteration of hormonal signal. We suggest that presence of allele Gln in genotype contributes increase of BMI, HOMO, leptin and triglyceride level, and decrease protective HDL.…”