title: Association of 1347 G/A cytochrome P450 4F2 (CYP4F2) gene variant with hypertension and stroke.
abstract: Genetic variants of cytochrome P450 4F2 (CYP4F2) gene have been suggested to be risk factors for hypertension, cardiovascular diseases and stroke. In the present case-control study we investigated the association of 1347 G/A polymorphism (rs2108622) in the 11th exon region of CYP4F2 gene with hypertension, ischemic stroke and stroke subtypes classified according to TOAST (Trial of Org 10172 in Acute Stroke Treatment) classification. Five hundred and seven stroke patients (hypertensives: normotensives = 279:228) and four hundred and eighty seven, age and sex matched controls (males: females = 356:131) (hypertensives: normotensives = 148:339) were involved in the study. The genotypes were determined by PCR-RFLP technique. Genotypes were confirmed by subjecting the PCR products to sequencing. Significant difference was observed in the genotypic distribution and allelic frequency between the stroke patients and healthy controls. AA genotype and A allele associated significantly with stroke and hypertension [P = 0.009; OR = 1.59 (95% CI = 1.119-2.283) and P = 0.010; OR = 1.26 (95% CI = 1.056-1.502); P = 0.01; OR = 1.58 (95% CI = 1.11-2.272) and P = 0.010; OR = 1.25(95% CI = 1.054-1.504) respectively]. A stepwise logistic regression analysis confirmed these findings. To establish that this polymorphism is associated with stroke independent of hypertension; we compared stroke patients without hypertension with normotensive controls. Significant difference was observed in genotypic distribution and allelic frequency between the two groups (P = 0.001 and 0.002 respectively). Evaluating the association of this polymorphism with stroke subtypes we found significant associations with cardioembolic stroke (P < 0.001). In conclusion our study suggests that 1347A allele of CYP4F2 gene is an important risk factor for hypertension and ischemic stroke.
authors.affiliation: Department of Molecular Biology, Institute of Genetics and Hospital for Genetic Diseases, Osmania University, Begumpet, Hyderabad 500016, India. anjanadurani@yahoo.co.in
authors.forename: Anjana
authors.initials: A
authors.lastname: Munshi
authors.forename: Vandana
authors.initials: V
authors.lastname: Sharma
authors.forename: Subhash
authors.initials: S
authors.lastname: Kaul
authors.forename: Amal
authors.initials: A
authors.lastname: Al-Hazzani
authors.forename: Ali A
authors.initials: AA
authors.lastname: Alshatwi
authors.forename: Gowhar
authors.initials: G
authors.lastname: Shafi
authors.forename: Rajeshwar
authors.initials: R
authors.lastname: Koppula
authors.forename: Sai Babu
authors.initials: SB
authors.lastname: Mallemoggala
authors.forename: A
authors.initials: A
authors.lastname: Jyothy
mesh_terms: D001483:Base Sequence; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics*; D000072470:Cytochrome P450 Family 4; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006801:Humans; D006973:Hypertension / Q000453:epidemiology* / Q000235:genetics*; D008297:Male; D008969:Molecular Sequence Data; D016017:Odds Ratio; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012307:Risk Factors; D017422:Sequence Analysis, DNA; D020521:Stroke / Q000453:epidemiology* / Q000235:genetics*
chemical_list: D003577:Cytochrome P-450 Enzyme System; D000072470:Cytochrome P450 Family 4; C117480:CYP4F2 protein, human