Association Between RORA Polymorphisms and Obesity.

RORα is a transcription factor encoded by RORA gene. This protein is involved in several metabolic conditions, including obesity. We assessed association between two polymorphisms within this gene (namely rs11639084 and rs4774388) and severe obesity in Iranian population. Both SNPs were associated with obesity in all models (P < 0.0001) except for over-dominant model. T allele of rs11639084 was associated with this trait with OR (95% CI) of 16.85 (13.11-21.67) and was considered as the risk allele. Allelic model best fit the data, since the AIC value for this model was the highest (AIC = 28.82). In the co-dominant model, TT genotype was associated with obesity with OR (95% CI) of 301.6 (137.4-662.1). This genotype was shown to be the risk genotype in the recessive model when compared with TC+CC (OR (95% CI) = 60.54 (30.35-120.7)). The C allele of rs4774388 was shown to be the risk allele with OR (95% CI) of 4.61 (3.72-5.71). In the recessive model, the CC genotype was associated with the mentioned trait with OR (95% CI) of 9.92 (6.62-14.8). This model best fit the data (AIC = 37.08). Cumulatively, the current study suggests contribution of RORα to the pathogenesis of obesity.

Association Between rs217727 and rs2839698 H19 Polymorphisms and Obesity.

Obesity is a worldwide health problem with an increasing trend. This condition has a significant genetic background. H19 lncRNA has been shown to protect from dietary obesity through decreasing levels of monoallelic genes in brown fat. In the current study, we aimed to find the association between two possibly functional H19 polymorphisms, namely rs217727 and rs2839698 and obesity in Iranian population. These polymorphisms have been shown to affect risk of some obesity-related conditions in different populations. The study included 414 obese cases and 392 controls. Notably, both rs2839698 and rs217727 were associated with obesity in the allelic model as well as all supposed inheritance models. In addition, after adjustment for gender, all P values remained significant. For rs2839698, the OR (95% CI) for T allele vs. C allele was 3.29 (2.67-4.05) (P-value < 0.0001). In the co-dominant model, both TT and CT genotypes were found to confer risk of obesity compared with CC genotype (OR (95% CI)= 14.02 (8.39-23.43) and 9.45 (6.36-14.04), respectively). Similarly, combination of TT and CT genotypes had an OR (95% CI) = 10.32 (7.03-15.17) when compared with CC genotype. For rs217727, the T allele was found to exert a protective effect (OR (95% CI) = 0.6 (0.48-0.75)). Moreover, in the co-dominant model, OR (95% CI) values for TT and TC genotypes vs. CC genotype were 0.23 (0.11-0.46) and 0.65 (0.49-0.87), respectively. Taken together, H19 polymorphisms may affect risk of obesity in Iranian population. It is necessary to conduct functional studies to confirm a causal relationship between the rs217727 and rs2839698 polymorphisms and obesity.

Associations between GRM7 polymorphisms and obesity in patients selected for sleeve gastrectomy.

Obesity is a worldwide problem in which genetic factors have a prominent role. We have selected two single nucleotide polymorphisms (SNPs) within glutamate metabotropic receptor 7 (GRM7) gene, namely rs6782011 and rs779867 to weigh their association with obesity in an Iranian cohort. The distribution of rs6782011 alleles was significantly different in the obese patients from normal controls (P < 0.0001; 434 obese patients vs. 297 normal controls). Distribution of alleles was also measured between sex-based groups of obese patients and controls. We detected remarkable differences between female obese cases and female control subjects (P < 0.0001; 374 female obese cases vs. 216 female normal controls); nevertheless, the difference in allele distribution was not significant for male cases compared with corresponding normal controls (p = 0.47; 60 male patients vs. 81 normal males). Contrariwise, distribution of rs779867 alleles was not significantly different between total obese patients compared with normal controls (P = 0.21; 434 obese patients vs. 297 normal BMI controls). There was also no significant difference for female and male obese patients compared with female and male normal BMI controls. Thus, GRM7 can be considered as a risk locus for obesity.