Distribution of SLC6A4 Gene Polymorphisms in a Multi-Ethnic Pakistani Cohort with Major Depressive Disorder

Muhammad Faisal Afridi; Shahbaz Ahmad  Zakki; Rafiullah Rafiullah; Kulsoom Farhat

doi:10.51253/pafmj.v76iSUPPL-8.14163

Authors

Muhammad Faisal Afridi Department of Public Health & Nutrition, The University of Haripur, KPK Pakistan
Shahbaz Ahmad Zakki Department of Public Health & Nutrition, The University of Haripur, KPK Pakistan
Rafiullah Rafiullah Department of Biotechnology, Balochistan University of Information Technology, Engineering, and Management Sciences, Quetta Pakistan
Kulsoom Farhat Department of Pharmacology, Army Medical College, Rawalpindi/National University of Medical Sciences (NUMS) Pakistan

DOI:

https://doi.org/10.51253/pafmj.v76iSUPPL-8.14163

Keywords:

Gene polymorphisms, Pakistan, Major Depressive Disorder, SLC6A4 gene, Selective serotonin reuptake inhibitors

Abstract

Objective: To determine the distribution of SLC6A4 gene polymorphisms (5-HTTLPR and rs25531) in a multi-ethnic Pakistani population with Major Depressive Disorders.

Study Design: Multi-center cross-sectional study.

Place and Duration of Study: Tertiary care hospitals in Quetta, Pakistan from Apr 2023 to Oct 2024.

Methodology: Four hundred thirty Pakistani patients with Major Depressive Disorder from five ethnic groups (Punjabi, Sindhi, Pathan, Baloch, Kashmiri) were enrolled. Genotyping for 5-HTTLPR and rs25531 polymorphisms was performed using allele-specific PCR followed by restriction fragment length polymorphism. Allele and genotype frequencies were calculated, Hardy-Weinberg equilibrium tested, and inter-ethnic comparisons made. Functional classification was based on tri-allelic system (LA, LG, S).

Results: A total of 430 participants were included in the study. Mean age was 32.29 ± 6.80 years. S allele was more common than the L allele, with frequencies of 494 (57.4%) and 366 (42.6%), respectively. Pathan group had the highest frequency of the L allele (47.3%) while Sindhi group had lowest (39.4%). LA allele was common in Pathans (36.5%) and least common in Sindhis (30.8%). Therefore, difference between in allele distribution and ethnic group was statistically significant as p value = 0.012 and differences in treatment response among the three genotype groups were also statistically significant as p value < 0.001.

Conclusion: Pakistani population shows unique SLC6A4 genetic architecture with S allele predominance (0.574) and substantial LA allele representation (0.324). The high frequency of low-expression genotypes suggests many Pakistanis may be genetically predisposed to variable SSRI responses. These population-specific data are crucial for developing pharmacogenetic

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