Molecular basis for the reduced catalytic activity of the naturally occurring T560M mutant of human 12/15-lipoxygenase that has been implicated in coronary artery disease.
We resequenced ALOX15 and then genotyped a common promoter and a less common novel coding SNP (T560M) in 1809 subjects with CAD and 1734 controls from Kaiser Permanente including a subset of participants of the Coronary Artery Risk Development in Young Adults study.
The carriers of the C allele (the CC homozygote and the CT heterozygote) of rs7217186:T>C and the carriers of the A allele (the AA homozygote and the GA heterozygote) of rs2619112</span>:G>A displayed elevated odds ratios (ORs) for CAD compared with the TT homozygotes and GG homozygotes, respectively, after adjusting for other potential confounders including age, sex, body mass index, systolic blood pressure, diastolic blood pressure, glucose, triglyceride, total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and smoking status (adjusted odds ratio [OR] = 3.2, 95% confidence interval [CI]: 1.335-7.665, P = 0.009 and adjusted OR = 3.5, 95% CI: 1.343-9.330, P = 0.011).
In summary, the present study shows that after adjustment for other confounding CAD factors, rs7217186</span>:T>C and rs2619112:G>A of ALOX15 are associated with increased risk of CAD in this Chinese Han population.