3 research outputs found
Role of CYP1A1 haplotypes in modulating susceptibility to coronary artery disease
349-355To
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 [m1 (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.
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