Implication of Leptin and Leptin Receptor Gene Variations in Type 2 Diabetes Mellitus: A Case-Control Study

Roohi Ashraf, Mosin Saleem Khan, Suhail Shafi Lone, Mohammad Hayat Bhat, Samia Rashid, Sabhiya Majid, Haamid Bashir

Abstract


Background: Global increase in the prevalence of type 2 diabetes mellitus (T2DM) has affected about 6% of the population and is one of the major healthcare challenges worldwide. Apart from other factors, genetics play a pivotal role in the development of diabetes. Recent studies have drawn attention to the role of leptin (LEP) and leptin receptor (LEPR) gene polymorphisms in the pathogenesis of T2DM, that being the reason for the uptake of this study.

Methods: A total of 390 T2DM cases and 408 controls matched with respect to age and gender were taken for the study. Biochemical analysis was performed on all study subjects. Polymerase chain reaction (PCR) amplification of the genomic regions encompassing the single nucleotide polymorphisms (SNPs) under study was followed by digestion using specific restriction enzymes to analyze the SNP genotype through restriction fragment length polymorphism (RFLP).

Results: Serum leptin levels were elevated in 57.9% (226 of 390) of cases as compared to 11.8% (48 of 408) of controls (P < 0.0001). Cases had significant homeostatic model assessment-insulin resistance (HOMA-IR) as compared to controls (5.3 ± 5.9 vs. 1.4 ± 0.4; P < 0.0001). In case of LEP G2548A SNP, the frequency of a variant genotype (GA + AA) was found to be higher for cases than controls (69.7% vs. 29.4%; P < 0.0001). For LEPR Q223R SNP, the frequency of a variant genotype (AG + GG) was found to be higher for cases than controls (69.2% vs. 23.6%; P < 0.0001).

Conclusion: We observed a significant association between the LEP/LEPR polymorphisms and T2DM in the ethnic population of Kashmir indicating that genetic susceptibility may play an important role in the pathogenesis of T2DM.




J Endocrinol Metab. 2022;12(1):19-31
doi: https://doi.org/10.14740/jem785

Keywords


Leptin; Leptin receptor; Polymorphism; T2DM; Restriction fragment length polymorphism

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