MTHFR (C677T) CT genotype and CT-apoE3/3 genotypic combination predisposes the risk of ischemic stroke

• The genetics of IS is complex with several risk factors and combination of genes.
• Predisposition of MTHFR CT genotype/T allele in south Indian IS patients.
• apoE was not associated with ischemic stroke patients from south India.
• Higher risk of ‘CT-apoE33’ genotypic combination for IS.

The predisposition to ischemic stroke (IS) might involve interactions of several genes and environmental factors. The present study was aimed to evaluate the influence of polymorphisms in methylenetetrahydrofolate reductase (MTHFR-C677T) and apolipoprotein-E (apo-E) as risk factors for IS patients in south Indian population. 200 IS patients and 193 age and sex matched controls were genotyped for MTHFR-C677T and apoE by Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP) method. Statistically significant association was observed for MTHFR CT genotype (IS-Pooled: OR = 4.29; p = 5.01 × 10− 5; IS-Males: OR = 4.13; p = 0.001; IS-Females: OR = 8.62; p = 0.027; IS-Large Vessel Disease (LVD)- Pooled: OR = 4.14; p = 0.0002) and T allele (IS-Pooled: OR = 4.82; p = 1.49 × 10− 5; IS-Males: OR = 4.33; p = 0.0002; IS-Females: OR = 7.99; p = 0.031; IS-LVD-Pooled: OR = 4.13; p = 0.0001). Further, reduced frequencies of CC genotype (IS-Pooled: OR = 0.20; p = 9.80 × 10− 6; IS-Males: OR = 0.25; p = 0.001; IS-Females: OR = 0.12; p = 0.027; IS-LVD-Pooled: OR = 0.23; p = 0.0001) and C allele (IS-Pooled: OR = 0.21; p = 1.49 × 10− 5; IS-Males: OR = 0.23; p = 0.0002; IS-Females: OR = 0.13; p = 0.031; IS-LVD-Pooled: OR = 0.24; p = 0.0001) were observed in IS patients than the controls. No association was observed for apoE genotypes/alleles in IS/LVD cases. Our study demonstrated the presence of risk for MTHFR CT genotype/T allele and ‘CT-3/3’ (n = 33 vs. 5; OR = 7.42; p = 0.001) genotypic combination in the development of IS in south India. Further, follow-up study of these stroke cases i.e., in later stages of the disease whether they are developing the neurological disorders such as Alzheimer's Disease (AD) and vascular dementia (VaD) is needed to draw a fruitful conclusion in connection between neurological disorders and with these two polymorphisms, before translating it into clinical practice.