RESUMEN
Stroke is a major cause of morbidity and mortality worldwide. Genetic and environmental factors are involved in the pathogenesis of stroke. Hypertension, diabetes mellitus, and cigarette smoking are the major risk factors, and smoking doubles the risk of ischemic stroke. Smoking cessation decreased the risk for ischemic stroke. CYP1A1 is the phase I metabolizing enzyme which plays a key role in metabolic activation of polycyclic aromatic hydrocarbons which are present in cigarette smoke and considered carcinogenic. So far, the association of CYP1A1 gene polymorphism with stroke has not been investigated in Indian population. So, the study is taken up to evaluate the association of this polymorphism with ischemic stroke in a South Indian population. We genotyped 215 ischemic stroke patients and 162 age-matched controls using polymerase chain reaction-restriction fragment length polymorphism. Statistical analysis showed that CYP1A1 "CC" genotype is associated with five times increased risk of ischemic stroke (odds ratio (OR) = 5.14; 95% confidence interval (95% CI) = 1.14-23.14, p = 0.01), while "TT" (OR = 0.78, 95% CI = 0.51-1.19, p = 0.25) and "TC" (OR = 1.04, 95% CI = 0.67-1.60, p = 0.85) genotypes were nonsignificant with the increased risk of stroke. T and C allele frequencies in stroke were 76.5% and 23.5% as against 81.8% and 18.2% in control group, respectively, thus, suggesting no statistically significant differences in the T (OR = 0.72, 95% CI = 0.50-1.03, p = 0.07) and C (OR = 1.37, 95% CI = 0.96-1.97, p = 0.07) allele frequencies between the two groups. The distribution of CYP1A1 genotypes and allelic frequency within the stroke subtypes showed a significant association of CC genotype only in intracranial large artery atherosclerosis (OR = 5.21, 95% CI = 1.03-26.38, p = 0.02) while other subtypes did not show any association. Further analysis of CYP1A1 genotypes in patients and control subjects with smoking habit also showed a similar trend. Hence, we conclude that the CYP1A1 CC genotype is associated with the increased risk of ischemic stroke.
RESUMEN
BACKGROUND: Osteoporosis is a multifactorial disorder with a strong genetic component and ESR1 is suggested as a candidate gene for osteoporosis. Therefore the present study is aimed to investigate the role of ESR1 gene polymorphisms and its influence on estradiol levels and BMD in osteoporotic women of Indian ethnicity. METHODS: Four-hundred twenty-seven osteoporotic women and 460 age matched controls were included in the study. ESR1 gene polymorphism was assessed by PCR-RFLP method. Serum estradiol was measured by ELISA. RESULTS: The frequency of pp and xx genotypes as well as p and x alleles was significantly high in pre- and postmenopausal osteoporotics when compared to controls (p<0.001). They had low BMD and estradiol levels in comparison with PP and XX genotype individuals (p<0.05). CONCLUSION: The ESR1 gene is associated with low bone mass and low estradiol levels in all our study subjects. It is likely that the allele exerts its influence on the bone in early adulthood leading to an increased risk of osteoporosis later in life.