Association of Candidate Gene Polymorphism with Metabolic Syndrome among Mongolian Subjects: A Case-Control Study

Abstract

Metabolic syndrome (MetS) is complex and determined by the interaction between genetic and environmental factors and their influence on obesity, insulin resistance, and related traits associated with diabetes and cardiovascular disease risk. Some dynamic markers, including adiponectin (ADIPOQ), brain-derived neurotrophic factor (BDNF), and lipoprotein lipase (LPL), are implicated in MetS; however, the influence of their genetic variants on MetS susceptibility varies in racial and ethnic groups. We investigated the association of single nucleotide polymorphism (SNP)-SNP interactions among nine SNPs in six genes with MetS’s genetic predisposition in Mongolian subjects. A total of 160 patients with MetS for the case group and 144 healthy individuals for the control group were selected to participate in this study. Regression analysis of individual SNPs showed that the ADIPOQ + 45GG (odds ratio (OR) = 2.09, p = 0.011) and P+P+ of LPL PvuII (OR = 2.10, p = 0.038) carriers had an increased risk of MetS. Conversely, G allele of LPL S447X (OR = 0.45, p = 0.036) and PGC-1α 482Ser (OR = 0.26, p = 0.001) allele were estimated as protective factors, respectively. Moreover, a haplotype containing the G-P+-G combination was related to MetS. Significant loci were also related to body mass index (BMI), systolic blood pressure (SBP), serum high-density lipoprotein cholesterol (HDL-C), triglyceride (TG), and fasting blood glucose (FBG), adipokines, and insulin as well as insulin resistance (p < 0.05). Our results confirm that ADIPOQ + 45T > G, LPL PvII, and PGC-1α Gly482Ser loci are associated with MetS in Mongolian subjects.

Development of a Structural Equation Model to Examine the Relationships between Genetic Polymorphisms and Cardiovascular Risk Factors

“…For example, there is a body of evidence that suggests that some genetic mutations or polymorphisms that occur in the genes of the lipid profile parameters [51][52][53] and metabolic markers [54][55][56][57] have a minimal or no effect on the outcomes of these CVR factors. While on the other hand, some studies have demonstrated a significant effect of polymorphisms on the CVR factors such as the lipid profile [58,59] and metabolic markers [60,61]. This inconsistency in all these reports is what makes the exact role of these polymorphisms on CVR factors still unclear and, therefore, warrants further investigations using a standardized approach with more robust genetic tools such as SEM [13].…”

Polymorphism in Adiponectin and Adiponectin Receptor Genes in Diabetes Mellitus Pathogenesis

“…The pathogenesis of nephropathy is tightly bound to glucose toxicity, increased blood pressure, and cholesterol levels, which, as mentioned earlier, were associated with the GG genotype of the ADIPOQ gene (+45T > G rs2241766) [ 23 ]. It was also discovered that the GG genotype of the ADIPOQ polymorphism (+45T > G rs2241766) is associated with the phenotypes of hypertension and dyslipidemia in Asian populations [ 24 ].…”

Association between Adiponectin and Leptin Receptor Genetic Polymorphisms and Clinical Manifestations of Metabolic Syndrome

“…This polymorphism is located at the 5′ end of the promoter region of LEP , and it is suggested that this region may contain inhibitory elements from transcription in adipocytes [ 10 ]. The G allele of the ADIPOQ (rs2241766) gene is associated with the risk of hypertension and dyslipidaemia [ 11 , 12 ]. The effect of this variant on pre-mRNA splicing or mRNA stability is well known, suggesting an allele-specific differential expression of adiponectin.…”