Genetic Bases of VitaminB12 Deficiency: Impact of MTHFR, TCN-II and GIF Polymorphisms on Vitamin B12 Level

Abstract

Vitamin B12 deficiency is associated with serious health problems such as neurological disorders. In Jordan, few studies have evaluated the level of vitamin B21 in the Jordanian population with different prevalence. Genetic predisposition, lifestyle, environment, socioeconomic status, and geographic have been linked to vitamin B12 deficiency. Polymorphisms in the GIF, MTHFR, and Transcobalamins, have been proposed to be associated with the level of vitamin B12. The aim of the current study was to evaluate the impact of certain polymorphisms in MTHFR, TCN-II and GIF genes on the level of vitamin B12 in the Jordanian population. Polymorphic sites of the MTHFR (c.677 C>T, rs1801133 and c.1286A>C, rs1801131), TCN2-776C>G (Arg259Pro) (rs1801198) and GIF-68 A>G (Q5R) genes were analyzed by RFLP and DNA sequencing in a group of vitamin B12 deficient individuals (n = 100). The control group included 100 matching individuals with a normal level of vitamin B12 (>200 ng/mL). Our results showed a significant association between the homologous variant of the TCN2 gene (G776G) and MTHFR c.677C>T genes and vitamin B12 deficiency. On the other hand, The MTHFR c.1286A>C variant and GIF variants did not show significant association with vitamin B12 deficiency. This study expounds the association of TCN2 and MTHFR polymorphisms with cobalamin levels in a Jordanian population and highlights the necessity of further studies to elucidate the molecular basis and impact of TCN2, GIF, and MTHFR gene polymorphisms on vitamin B12 deficiency and associated disorders.