Genetic variants in DBC1 , SIRT1 , UCP2 and ADRB2 as potential biomarkers for severe obesity and metabolic complications

Obesity is a multifactorial disease associated with the development of many comorbidities. This disease is associated with several metabolic alterations; however, it has been shown that some individuals with obesity do not exhibit metabolic syndrome. Adipose tissue neutralizes the detrimental effects of circulating fatty acids, ectopic deposition, and inflammation, among others, through its esterification into neutral lipids that are stored in the adipocyte. However, when the adipocyte is overloaded, i.e., its expansion capacity is exceeded, this protection is lost, resulting in fatty acid toxicity with ectopic fat accumulation in peripheral tissues and inflammation. In this line, this study aimed to investigate whether polymorphisms in genes that control adipose tissue fat storage capacity are potential biomarkers for severe obesity susceptibility and also metabolic complications. This study enrolled 305 individuals with severe obesity (cases, BMI≥35 kg/m ) and 196 individuals with normal weight (controls, 18.5≤BMI≤24.9 kg/m ). Demographic, anthropometric, biochemical, and blood pressure variables were collected from the participants. Plasma levels of leptin, resistin, MCP1, and PAI1 were measured by Bio-Plex 200 Multiplexing Analyzer System. Genomic DNA was extracted and variants in (rs17060940), (rs7895833 and rs1467568), (rs660339), (rs1801282) and (rs1042713 and rs1042714) genes were genotyped by PCR allelic discrimination using TaqMan assays. Our findings indicated that rs7895833 polymorphism was a risk factor for severe obesity development in the overdominant model. rs1467568 and rs660339 were associated with anthropometric traits. rs1467568 G allele was related to lower medians of body adipose index and hip circumference, while the rs660339 AA genotype was associate with increased body mass index. Additionally, rs17060940 influenced glycated hemoglobin. Regarding metabolic alterations, 27% of individuals with obesity presented balanced metabolic status in our cohort. Furthermore, rs1467568 AG genotype increased 2.5 times the risk of developing metabolic alterations. No statistically significant results were observed with and polymorphisms. This study revealed that rs7895833 and rs1467568 are potential biomarkers for severe obesity susceptibility and the development of unbalanced metabolic status in obesity, respectively. rs660339 and rs17060940 also showed a significant role in obesity related-traits.