Corroborating evidence for the correlation between the MTHFR C677T single nucleotide variant and smoking in Croatian subjects independent of ischemic stroke

Abstract

Hyperhomocysteinaemia is a risk factor for ischemic stroke development. Single nucleotide variation in the methylenetetrahydrofolate reductase gene (MTHFR, C677T polymorphism, T allele) causes a Ala222Val mutation that is associated with hyperhomocysteinemia, cardiovascular disease and stroke. The homozygous TT genotype of MTHFR may also be linked to tobacco smoking in patients from distinct demographic groups. This study evaluated the association of T allele with smoking in a cohort of 301 Croatian adults, including 187 healthy controls and 114 patients with ischemic stroke (IS) and proven ischemic cerebral infarction based on Computed Tomography (CT). Exclusion criteria were hemorrhagic cerebral infarction on CT scan, medical history of diabetes mellitus, and age (>60 years). Cholesterol, triglycerides (TG), low-density lipoprotein (LDL), high-density lipoprotein (HDL) and C-reactive protein (CRP) were biochemically analyzed. A positive correlation between the TT genotype of MTHFR and smoking was observed within our entire study cohort (p = 0.011). In the control group, the relative frequency of the TT genotype in smokers is complemented by the prevalence of the CC genotype among non-smokers. Hence, our study with Croatian subjects corroborates previous studies indicating that the TT MTHFR variant is linked to smoking. This positive correlation between the TT genotype and smoking represents a confounding parameter that must be accounted for to permit evaluation of statistical associations with stroke and biochemical markers in blood and single nucleotide variations in the MTHFR gene.