Association of Resistin Gene 3′-Untranslated Region +62G→A Polymorphism with Type 2 Diabetes and Hypertension in a Chinese Population

Abstract

Resistin, a recently discovered polypeptide, antagonizes insulin action and may play a part in the pathogenesis of insulin resistance. This study investigates whether resistin gene polymorphism can be associated with type 2 diabetes. We studied 1102 Chinese type 2 diabetes patients and 743 subjects without diabetes. The resistin 3'-untranslated region (UTR) +62G-->A polymorphism was determined by PCR. Type 2 diabetes subjects had a lower frequency of resistin gene 3'UTR +62A allele (GG:GA/AA, 83.5%:16.5%) than the controls (GG:GA/AA, 75.1%:24.9%; odds ratio, 1.524; 95% confidence interval, 1.268-1.831; P < 0.001). Unexpectedly, diabetic patients with the GG genotype had a higher prevalence of hypertension (GG:GA/AA, 49.8%:36.2%; odds ratio, 1.375; 95% confidence interval, 1.116-1.693; P = 0.001). Logistic regression analysis confirmed that the resistin gene 3'UTR +62G-->A polymorphism acts as an independent contributing factor to type 2 diabetes and hypertension. The mean systolic and diastolic blood pressure levels in diabetic subjects with the GG genotype (144 +/- 21/87 +/- 13 mm Hg) were significantly higher than those in subjects with GA/AA variants (139 +/- 21/84 +/- 14 mm Hg; P = 0.004 and P = 0.002, respectively). Multiple linear regression analysis showed resistin gene polymorphism to be an independent factor associated with systolic and diastolic blood pressures in type 2 diabetes patients. These findings suggest that resistin may play a role in the pathogenesis of type 2 diabetes and insulin resistance-related hypertension.

Plasma resistin concentration determined by common variants in the resistin gene and associated with metabolic traits in an aged Japanese population

“…Although SNPs in the promoter region of RETN have previously been associated with the circulating resistin level [21,23,25,29], only one previous study has demonstrated an association between resistin level and rs34861192 [29]; in that study, the number of participants was smaller than that in the present study. The rs3745368 polymorphism (also known as +62G→A) in the 3′ untranslated region of RETN has previously been associated with hypertension and type 2 diabetes [18,19,22]. , respectively (corrected by the Bonferroni method by multiplying the raw p values by 11).…”

“…Some studies have demonstrated an association between increased serum resistin concentration and metabolic disorders, including obesity, insulin resistance, type 2 diabetes, hypertension, dyslipidaemia and atherosclerotic cardiovascular disease [9][10][11][12][13][14][15]. Moreover, polymorphisms of the human resistin gene (RETN) have also been found to be associated with such disorders [16][17][18][19][20][21][22][23][24][25]. However, not all studies have reproduced such findings [26][27][28].…”

Resistin Promotes Smooth Muscle Cell Proliferation Through Activation of Extracellular Signal–Regulated Kinase 1/2 and Phosphatidylinositol 3-Kinase Pathways

“…15,16 Nevertheless, some genetic case-control studies have demonstrated that polymorphisms of the human resistin gene have been linked to insulin resistance in certain populations. [21][22][23] Moreover, resistin expression is positively correlated with insulin resistance in humans, 24,25 and serum resistin levels are elevated in human obesity 26 and type 2 diabetes. 17 The plasma concentrations of resistin in patients with insulin resistance remain to be carefully defined, although preliminary studies suggest that mean circulating resistin levels may be 40 ng/mL in diabetes (versus 15 ng/mL in lean nondiabetic patients).…”

Variation in the resistin gene is associated with obesity and insulin-related phenotypes in Finnish subjects

“…We genotyped four previously identified non-coding SNPs: −420C>G (rs1862513) from the promoter region [12,13,14,15,17], +156C>T (rs3219177) [13,14,15,17,18,21] and +298G>A (rs3745367) [14,17,18,19] from intron 2, and +1084G>A (rs3745368) from the 3′ untranslated region (UTR) on exon 4 [16,21] of the resistin gene on chromosome 19. These four SNPs were chosen because they had shown evidence of association with Type 2 diabetes-related traits in other study samples [12,13,14,15,16]. The SNPs had an allele frequency of >0.1 in Caucasians, and comprised four of the six common (>0.1) variations identified in previous studies that screened both coding and regulatory regions of the gene for polymorphisms [13,14,15,17,18,20,21].…”

“…Non-coding variants of the gene have been identified [12,13,14,15,16,17,18,19,20,21,22] and have been shown to be associated with variables related to weight [12,13], insulin [14,15] and blood pressure [16]. A recent study reported that a polymorphism in the promoter region was associated with resistin mRNA levels in abdominal subcutaneous fat [12].…”