title: Role of CYP1A1 haplotypes in modulating susceptibility to coronary artery disease.
abstract: To investigate the role of cytochrome P450 1A1 (CYP1A1) haplotypes in modulating susceptibility to coronary artery disease (CAD), a case-control study was conducted by enrolling 352 CAD cases and 282 healthy controls. PCR-RFLP, multiplex PCR, competitive ELISA techniques were employed for the analysis of CYP1A1 [ml (T-->C), m2 (A-->G) and m4 (C-->A)] haplotypes, glutathione-S-transferase (GST)T1/GSTM1 null variants and plasma 8-oxo-2'deoxyguanosine (8-oxodG) respectively. Two CYP1A1 haplotypes, i.e. CAC and TGC showed independent association with CAD risk, while all-wild CYP1A1 haplotype i.e. TAC showed reduced risk for CAD. All the three variants showed mild linkage disequilibrium (D': 0.05 to 0.17). GSTT1 null variant also exerted independent association with CAD risk (OR: 2.53, 95% CI 1.55-4.12). Among the conventional risk factors, smoking showed synergetic interaction with CAC haplotype of CYP1A1 and GSTT1 null genotype in inflating CAD risk. High risk alleles of this pathway showed dose-dependent association with percentage of stenosis and number of vessels affected. Elevated 8-oxodG levels were observed in subjects with CYP1A1 CAC haplotype and GSTT1 null variant. Multiple linear regression model of these xenobiotic variants explained 36% variability in 8-oxodG levels. This study demonstrated the association of CYP1A1 haplotypes and GSTT1 null variant with CAD risk and this association was attributed to increased oxidative DNA damage.
authors.affiliation: Department of Clinical Pharmacology & Therapeutics, Nizam's Institute of Medical Sciences, Hyderabad 500082, India.
authors.forename: Sana Venkata Vijaya
authors.initials: SV
authors.lastname: Lakshmi
authors.forename: Shaik Mohammad
authors.initials: SM
authors.lastname: Naushad
authors.forename: Kankanala
authors.initials: K
authors.lastname: Saumya
authors.forename: Damera Seshagiri
authors.initials: DS
authors.lastname: Rao
authors.forename: Vijay Kumar
authors.initials: VK
authors.lastname: Kutala
mesh_terms: D000328:Adult; D000368:Aged; D003324:Coronary Artery Disease / Q000201:enzymology / Q000453:epidemiology* / Q000235:genetics*; D019363:Cytochrome P-450 CYP1A1 / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease / Q000453:epidemiology* / Q000235:genetics*; D006239:Haplotypes / Q000235:genetics*; D006801:Humans; D007194:India / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D015995:Prevalence; D018570:Risk Assessment; D012307:Risk Factors
chemical_list: D019363:Cytochrome P-450 CYP1A1