Relationship of phosphodiesterase 4D (PDE4D) gene polymorphisms with risk of ischemic stroke: a hospital based case-control study.
Stroke remains a leading cause of death and disability worldwide. Ischemic stroke (IS) accounts for around 80-85% of total stroke and is a complex polygenic multi-factorial disorder which is affected by a complex combination of vascular, environmental, and genetic factors. The study was conducted with an aim to examine the relationship of single nucleotide polymorphisms (SNPs) of PDE4D (T83C, C87T, and C45T) gene with increasing risk of IS in patients in North Indian population. In this hospital-based case-control study, 250 IS subjects and 250 age-and sex-matched control subjects were enrolled from the Neurosciences Centre, A.I.I.M.S., New Delhi, India. Deoxyribonucleic acids (DNAs) were extracted using the conventional Phenol-Chloroform isolation method. Different genotypes were determined by Polymerase chain reaction- Restriction fragment length polymorphism method. Odds ratio (OR) and 95% Confidence Interval (CI) of relationship of polymorphisms with risk of IS were calculated by conditional multivariable regression analysis. High blood pressure, low socioeconomic status, dyslipidemia, diabetes, and family history of stroke were observed to be statistically significant risk factors for IS. Multivariable adjusted analysis demonstrated a statistically significant relationship between SNP 83 of PDE4D gene polymorphism and increasing odds of IS under the dominant model of inheritance (OR, 1.59; 95% CI, 1.02 to 2.50; p value = 0.04) after adjustment of potential confounding variables. Stratified analysis on the basis of TOAST classification demonstrated a statistically significant association for increasing 2.73 times odds for developing large vessel disease stroke as compared to controls (OR, 2.73; 95% CI, 1.16 to 0.02; p value = 0.02). We did not find any significant association of SNPs (C87T and C45T) of the PDE4D gene with the risk of IS. SNP 83 of PDE4D gene may increase the risk for developing IS whereas SNP 87 and SNP45 of PDE4D may not be associated with the risk of IS in the North Indian population. Prospective cohort studies are required to corroborate these findings.