Importance of gene variants and co-factors of folate metabolic pathway in the etiology of idiopathic intellectual disability

Abstract

Different components of the folate metabolic cycle are crucial for maintaining integrity of DNA. The present study was aimed at exploring the role of some important constituents of the folate cycle in the etiology of idiopathic intellectual disability (IID). Nuclear families with IID probands (n = 226) and ethnically matched controls (n = 181) were recruited for micronucleus, karyotype, genetic polymorphism (MTR rs1805087, MTRR rs1801394, and DHFR rs70991108), folate, vitamin B6, vitamin B12, and cysteine analysis. Significant difference in genotype frequencies in IID probands and their parents were observed for rs1805087 (P = 0.03, 0.02), rs1801394 (P = 0.03, 0.001), and rs70991108 ((P = 0.03, 0.02) as compared to controls. IID probands showed significantly higher micronucleus frequency (P = 0.01) and decreased vitamin B6 level (P = 0.002). A strong correlation between rs1801394 ‘G’ allele and micronucleus was also noticed. From the present investigation, a role of genetic polymorphisms and vitamin B6 levels could be hypothesized in the etiology of IID.