Association of vitamin B12 transporter protein (transcobalamin II) genetic polymorphisms with risk of stroke: An observational pilot study in north Indian population

Abstract Background Vitamin B12 is an essential coenzyme for homocysteine remethylation. So, its deficiency could lead to homocysteine accumulation, a modifiable risk factor for coronary artery disease, deep vein thrombosis and stroke. Transcobalamin II (TCN2) protein responsible for intracellular delivery of vitamin B12 levels, might have change in structure due to genetic variation leading to the altered delivery of vitamin B12. TCN2 gene polymorphism has been associated with increased risk of coronary artery disease, however to the best of our knowledge, no previous study has documented its effect in stroke in India. Aim To explore TCN2 gene polymorphisms status and its association with risk of stroke in North Indian population. Methods An observational study including 154 subjects (84 stroke cases and 70 healthy) was conducted. Genotyping of TCN2 gene SNP 776C > G was done by PCR-RFLP and that of 1196G > A and 1043C > T by allele-specific PCR. Serum level of vitamin B12, and homocysteine were measured by ELISA, and Enzymatic Cycling method respectively. Results Subjects with 776GG genotype had 2.5 times higher risk of developing stroke as compared to 776CC genotype (OR = 2.5, 95%CI = 1.06–5.88; P = .04). Moreover, 776GG had a significantly lower vitamin B12 (P = .04) and a significantly higher homocysteine (P = .004) as compared to 776CC. SNP 1196G > A did not show a significant association with risk of stroke, vitamin B12 and homocysteine levels. 1043CT genotype showed significantly lower risk of stroke (OR = 0.34, 95%CI = 0.13–0.90; P = .03), though had no significant association with vitamin B12 and homocysteine levels. Conclusion SNP 776C > G may be used as a genetic marker for predicting increased risk of stroke. Whereas, 1043CT genotype may have a protective association against the risk of stroke.