Interethnic Differences in Single and Haplotype Structures of Folylpolyglutamate Synthase and Gamma-glutamyl Hydrolase Variants and Their Influence on Disease Susceptibility to Acute Lymphoblastic Leukemia in the Indian Population: An Exploratory Study

Abstract

AbstractAim: We aim to establish the genotype and haplotype frequencies of folylpolyglutamate synthase (FPGS rs10106 and rs1544105) and gamma-glutamyl hydrolase (GGH rs3758149 and rs11545078) variants in the South Indian population (SI) and to study the association of these variants with susceptibility to acute lymphoblastic leukemia (ALL). We also aim to compare the genotype and haplotype frequencies of studied variants with those of superpopulations from the 1000 Genomes Project collected in phase-3 and other published studies in the literature. Materials and Methods: A total of 220 unrelated healthy volunteers and 151 patients with ALL of both sexes were recruited for the study. Extracted DNA was subjected to genotyping by allelic discrimination using quantitative real-time-polymerase chain reaction. Genotype details of the studied variants in other ethnicities were obtained from 1000 genomes project Phase 3 data. Haploview software was used to construct haplotypes. Results:: In our study, the frequencies of FPGS rs1006'G' and rs1544105'A' alleles were found to be 37% and 37.2%, respectively, and the frequencies of GGH rs3758149'T' and GGH rs11545078'T' alleles were found to be 29.8% and 16.7%, respectively. Among the studied variants, FPGS rs1544105'AA' genotype carriers were found to be susceptible to the risk of ALL (odds ratio: 2.16; 95% confidence interval [CI]: 1.15–4.07; P = 0.02). Haplotype structures of FPGS and GGH variants in SI population were significantly different from other ethnicities (P < 0.05), except the South Asian superpopulation. Conclusion: FPGS rs1544105'AA' genotype was found to influence the risk for ALL. Intra and interethnic differences exist in the distribution of studied variants. Therefore, the impact of each variant on the susceptibility and outcome of diseases may differ between populations.