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Investigating the Regulatory Effects of LEP rs7799039 Polymorphism on Obesity through In-vitro and In-silico Analysis

genetics
molecular-biology
nutrition
medical-genetics

Abstract

Backgraund. The LEP rs7799039 polymorphism has been identified as a potential genetic factor linked to obesity. Therefore, in this study, the association between the LEP rs7799039 polymorphism and obesity were investigated through in-silico and in-vitro analyses in the Turkish population.
Methods. A total of 183 individuals with obesity and 138 healthy controls were genotyped for the LEP rs7799039 polymorphism using TaqMan ® allelic discrimination assays. Allele and genotype frequencies were compared using Fisher’s exact test and chi-square (χ²) tests in Jamovi, with odds ratios (ORs) calculated. Functional effects of SNPs were assessed through bioinformatics tools including PredictSNP2, CADD, and GWAVA. Transcription factor binding sites in LEP promoter were analyzed using PROMO_v3.02 and JASPAR2024, and nucleosome positions were predicted using NuPoP package in R, and CpG islands were identified using the DBCAT tool.
Results. The A/A genotype was more prevalent in the patients with obesity (56.8%) compared to controls (36.2%), and the A allele frequency was also higher in individuals with obesity (68.3%) compared to controls (36.2%). In codominant, dominant, and recessive models, the A/A genotype showed odds ratios (OR) of 2.81 (95% CI: 1.63- 4.84), 2.24 (95% CI: 1.36-3.70), and 2.32 (95% CI: 1.47-3.65), respectively. In conclusion, LEP rs7799039 polymorphism as a potential genetic marker for obesity risk, highlighting the importance of transcription factor interactions involved in metabolic and glucocorticoid pathways by altering leptin gene regulation. This is among the first studies to examine transcription factor binding alterations at rs7799039 polymorphism, highlighting the importance of transcription factor-mediated gene expression changes in complex traits.
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