Leptin and Leptin Receptor Gene Variants and Their Association with Antipsychotic-Induced Weight Gain in a Sri Lankan Schizophrenia Cohort

Antipsychotic-induced weight gain (AIWG) is a significant clinical challenge. Leptin (LEP) and Leptin receptor (LEPR) play crucial roles in appetite and energy homeostasis, making them plausible candidates for influencing AIWG. This study investigated the associations of LEP and LEPR gene polymorphisms with AIWG in a Sri Lankan population. Five single nucleotide polymorphisms (SNPs), rs1137101 and rs1327118 (LEPR), and rs10954173, rs3828942, and rs2167270 (LEP), were genotyped via competitive amplification of differentially melting amplicons (CADMA) with high-resolution melt analysis (HRMA) and validated via the MassARRAY System. Statistical analyses, including association, interaction, and haplotype analyses, were performed using the SNPstats online tool. While initial analyses revealed only an association between rs1327118 and AIWG (odds ratio (OR): 1.80, 95% CI: 1.09–2.97, p = 0.02) in the dominant model, interaction analyses revealed significant drug-specific effects for LEP variants such as rs3828942 (protective effect of olanzapine) and rs2167270 (susceptible for weight gain against clozapine). Haplotype analyses also suggested a statistical tendency of the GGG haplotype of LEP variants (p = 0.053), highlighting the complex interplay of genetic and environmental factors in AIWG.