Homologous G776G Variant of Transcobalamin-II Gene is Linked to Vitamin B12 Deficiency

Abstract

Abstract. Vitamin B12 (Cobalamin) deficiency, due to improper internalization of cobalamin, is a metabolic disorder prevalent in impoverished and elderly populations and is associated with megaloblastic anemia and dementia. It has been suggested that mutations in transcobalamin II ( TCN2) or gastric intrinsic factor (GIF) proteins can alter their binding efficiency to cobalamin or reduce the ability of their receptors to internalize them. In this case-control study, the correlation between vitamin B12 deficiency and alternative alleles of TCN2 and GIF was investigated in a Jordanian population. One hundred individuals with vitamin B12 deficiency (B12 < 200 mg/mL) were enrolled in our study to evaluate the TCN2 and GIF polymorphisms. The control group (B12 > 200 mg/mL) included 100 individuals. Our results indicated a significant association between the homologous variant of the TCN2 gene (G776G) and vitamin B12 deficiency, and an intermediate phenotype in heterozygous individuals ( p < 0.001, OR = 5.6, 95% CI = 2.95 to 10.63). The GIF gene, however, showed no correlation between the A68G variant and vitamin B12 deficiency ( p = 0.2). This study expounds the association of TCN2 polymorphism with cobalamin levels in a Jordanian population and highlights the necessity of further studies to elucidate the molecular basis and impact of TCN2 and GIF genes polymorphisms on vitamin B12 deficiency and associated disorders.