Association of −394C>G and −420C>G polymorphisms in the RETN gene with T2DM and CHD and a new potential SNP might be exist in exon 3 of RETN gene in Chinese

Abstract

Genetic variations of the human RETN gene are associated with metabolic phenotypes, including obesity, insulin sensitivity, diabetes, and coronary heart disease (CHD). There are few studies of two gene variants, -394C>G and -420C>G, in Chinese population. This study investigated the distribution of RETN gene, single nucleotide polymorphisms (SNPs), in Chinese Han population and the association of the polymorphisms with type 2 diabetes mellitus (T2DM) and CHD. In a population-based, case-control genetic association study, a total of 961 subjects were recruited from the community, including 318 T2DM patients, 273 CHD patients, and 370 unrelated healthy control individuals. Serum lipid levels were detected. Two SNPs of RETN gene, -394C>G and -420C>G, were genotyped by PCR-RFLP. Unknown Polymorphisms were screened with the technique of denaturing high performance liquid chromatography (DHPLC). The frequencies of RETN -394G allele in T2DM group, CHD group, and control group were 0.3066, 0.3555, and 0.3481, respectively, which are met with the Hardy-Weinberg equilibrium. There is a significant difference of the comparison of sex in T2DM group of RETN gene SNP-394C>G (P < 0.05). Compared with controls, there was no significant difference in the distribution of genotypes and allele frequencies of -394C>G polymorphic site in T2DM patients and CHD patients, respectively. No direct association was found between the -394C>G polymorphism and T2DM or CHD. The frequencies of RETN -420G allele in T2DM group, CHD group, and control group were 0.4009, 0.3725, and 0.3859, respectively, which are met with the Hardy-Weinberg equilibrium. The frequencies of RETN -420G allele in T2DM groups and control groups of Chinese population are significantly different from those in European population (0.40 vs. 0.27, 0.39 vs. 0.26) (P < 0.01). Compared with controls, there was no significant difference in distribution of genotypes and allele frequencies of -420C>G polymorphic site in T2DM patients and CHD patients, respectively. No direct association was found between the -420C>G polymorphism and T2DM or CHD. In addition, we found new potential SNP +593G>C in exon 3 of RETN gene using DHPLC. The RETN gene exhibits sex and ethnic differences. +593G>C of RETN gene might be a new potential SNP in exon 3 of RETN gene. Association between SNP -394C>G and -420C>G of RETN gene with T2DM and CHD in Chinese needs more exploration.

Association Between FourResistinPolymorphisms, Obesity, and Metabolic Syndrome Parameters in Tunisian Volunteers

“…The lack of association between 44G/A, 62G/A, and 394C/G SNPs and obesity risk in our study was also reported in many studies (Cao and Hegele, 2001;Wang et al, 2002;Sentinelli et al, 2002;Chi et al, 2009;Hivert et al, 2009;Asano et al, 2010). Therefore, the effect of SNPs on obesity is quite variable.…”

“…The genotypes for each resistin polymorphism 420C/G and 394C/G [promoter] and 44G/A and 62G/A [3¢-UTR] were determined by polymerase chain reaction (PCR)-restriction fragment length polymorphism as described by Cao and Hegele (2001), Duman et al (2007), Tang et al (2008), and Chi et al (2009). PCR products and the digest product were resolved by 2% agarose gel electrophoresis and visualized by ethidium bromide staining.…”

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.…”

“…Solaleh and Motawi found in Asians and Africans [9,8], an augmented risk of developing T2D was associated with the g.-420C>G polymorphism, whereas Chi and Chen found in Asia and Northern America no risk [23,24]. In the same manner, in Africans there was a positive association between obesity and the g.-420C>G polymorphism [25,26]; whereas, Apasalamy failed to observe any change in risk [19].…”