| BackgroundCoronary artery disease (CAD) is not only a major cause of death and disability in western countries, but also become an important cause of morbidity and mortality in China. The pathogenesis of CAD is very complex, which is now considered that CAD is caused by genetic and environmental factors. Recently, the role of gene in the pathogenesis of CAD attracts more and more attention. Arachidonate 12/15-lipoxygenase (12/15-LOX) can induce the development of CAD by multiple mechanisms. ALOX15 is the gene that encodes the human 12/15-LOX. Some researchers have detected the association of the single nucleotide polymorphisms (SNPs) of ALOX15 with CAD or carotid atheromatous plaque, but the detected conclusions are not accordant with one another. And there are no related reports in China. Our study aims to investigate whether the SNPs of ALOX15 are associated with susceptibility to CAD, and then provide basis for early diagnosis and prophylaxis of CAD.Objectives1. To research the distribution of the genotypes and alleles of rs7217186 and rs2619112 in the Chinese Han population from Shandong Province.2. To evaluate the association of ALOX15's polymorphisms, rs7217186 and rs2619112, with the susceptibility to CAD.Subjects and methodsWe adopted the method of the case-control study. From September 18,2006 to March18,2008, a total of 1127 subjects were recruited in Qilu Hospital, Shandong University, China. The CAD group consisted of 519 CAD patients (362 males,157 females,61.3±10.755 year of age) consecutively recruited from the inpatients in this hospital and were confirmed by coronary angiography to have one or more coronary arteries with≥50% luminal stenosis. Those with history of other diseases such as hyperthyroidism, secondary hypertension, chronic liver disease, chronic renal disease, acute infection and hematologic diseases were not included in this study. As the control group, we selected 608 healthy adults (401 males,207 females,60.4±10.730 year of age) matched for gender and age presented at our Hospital for the annual health examination. The genotypes of rs7217186 and rs2619112 were selected and genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The relationship between the SNPs of ALOX15 and CAD were determined.Results1. Clinical characteristics of the control group and CAD group:There was no difference in age or gender between the CAD patients and the healthy adults (P>0.05). Compared to the control group, the CAD group had higher BMI, SBP, DBP, as well as higher levels of Glu, TG and LDL-C but lower level of HDL-C (all P<0.05). However, the serum level of TC from the CAD group was nearly equal to that from the control group (P>0.05).2. Associations of the polymorphisms (rs7217186 and rs2619112) with CAD(1) Distribution of the genotypes and alleles of rs7217186 and rs2619112 in the two groups:There was no significant difference in the distribution of the three genotypes at either loci of rs7217186 and rs2619112 between the CAD and control group (both P>0.05). The frequencies of the two alleles were also comparable between CAD and control group at both loci (both P>0.05). After adjusting for other potential confounders including age, gender, BMI, SBP, DBP, Glu, TG, TC, HDL-C, LDL-C and smoking status, the distribution of the genotypes of rs2619112 was still similar between the two groups (P=0.051). However, there was a significant difference in the distribution of genotypes at rs7217186 between the two groups (P＜0.05). (2) The association between ALOX15 genotypes and the severity of CAD:There was no association between the number of affected coronary arteries and the two polymorphisms (P>0.05), and Gensini score was not significantly different in the genotypes of rs7217186 or rs2619112.(3) The association between ALOX15 genotypes and CAD in the dominant and recessive manners:The two SNPs are not associated with CAD in the dominant or recessive manner by single factor analysis. But after adjusting those aforementioned confounders, the CC homozygote and the CT heterozygote of rs7217186 showed a significantly higher risk of CAD compared with the TT homozygote (P<0.05), and the AA homozygote and the AG heterozygote of rs2619112 also showed a higher risk than the GG homozygote (P＜0.05).(4) The associations between rs7217186 or rs2619112 and CAD in age subgroup: The allele C for rs7217186 and the allele A for rs2619112 each significantly increased the risk of CAD in subjects with age< 60 years after adjusting those aforementioned confounders (P<0.05), while in subjects of≥60 years, the statistical significance was not detected in the two polymorphic sites (P> 0.05).(5) The associations between rs7217186 or rs2619112 and CAD in gender subgroup:After adjusting those confounders, CC and CT genotypes of rs7217186 were found to have a higher risk of CAD in female subjects (P<0.05), while the AA and GA genotypes of rs2619112 displayed a significantly increased risk of CAD only in male subjects (P<0.05). The association between the polymorphism and CAD risk was not statistically significant in males for rs7217186 or females for rs2619112.(6) Haplotype analyses of SNPs:In our study, four haplotypes were formed by the two SNPs, including CA, CG, TA and TG. The distribution of the four haplotypes was showed no significant difference between the two groups (P>0.05).Conclusions1. rs7217186 of ALOX15 was associated with CAD, and the C allele was an independent predictor of CAD, which had a higher risk in young adult or in female.2. rs2619112 of ALOX15 was associated with CAD, and the A allele was an independent predictor of CAD, which had a higher risk in young adult or in male. 3. rs7217186 and rs2619112 were not associated with the severity of CAD.4. The four haplotypes formed by rs7217186 and rs2619112 of ALOX15, were not significantly associated with the susceptibility to CAD. |
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