The Study On Relationship Between Polymorphism Of LRP6 Gene And Coronary Atherosclerosis

Background:Coronary heart disease is a multi-factor disease. The risk factors include age, smoking, hypertension, diabetes and genetic factors. According to the investigation on the coronary heart disease susceptibility, the incidence of coronary heart disease varies among different populations, even the same race in the same living condition. The genetic factors of coronary heart disease determine the individual susceptibility to external pathogenic factors. Therefore, in recent years, more and more researches have focused on the gene polymorphism of coronary artery disease. In the year of 2007,a large sample from an Iranian family demonstrated the correlation between autosomal dominant inheritance and premature coronary heart disease, hyperlipidemia, hypertension, type 2 diabetes and osteoporosis, which was attributed to C-to-T transition in exon 9 on the LRP6 gene, resulting in an arginine-to-cysteine substitution at codon 611 (R611C). The index case in this family was found to be homozygous for this mutation; while all other affected family members were heterozygous for the mutation, they still manifested premature coronary artery disease and metabolic syndrome. So far, research on that gene has not been reported.Objective:To investigate the relationship between LRP6R611C polymorphism and the susceptibility of coronary artery disease(CAD)in Han population in Ji Lin province.Methods:The genetic polymorphism of LRP6R611C was detected by Polymerase chain reaction/restriction fragment length polymorphism(PCR-RFLP)in 96 CAD patients and 98 control group patients who were diagnosed by coronary angiography.Results:The frequencies of R allele (CSP45I-treated PCR products with 171bp fragment) and C alleles (CSP45I-treated PCR products without 171bp fragment) were 0.86 and 0.14 respectively. The frequencies of R and C alleles were 86.5% and 13.5% in CAD group, compared with 85.7% and 14.3% in control group. There was no statistically significant difference between CAD group and control group in R/C allele frequencies and three genotype frequencies(RR/RC/RR)(P>0.05). Further statistical analysis showed that the incidence of coronary heart disease had no significant increase in the individuals who carry a mutant C allele than those with wild type -611RR(.OR=0.8765,95% CI=0.432-1.5324,P=0.721)And the result remain the same when we have adjusted the discrepancy of age,sex,hypertension,hyperlipidmia,smoking,diabetes and other risk factors by Logistic regression methods.(OR=0.7624,95%CI=1.01-6.03,P=0.736).Conclusion:Frequencies of the alleles and genotypes of R611C position of LRP6 gene were not significantly different between the CAD group and the control group.Compared with carriers with the wild type -611RR,the incidence of coronary heart disease in the individuals who carry mutant C allele had no significant difference, even our data has been adjusted by logistic regression methods, which should not be considered as a risk factor of cardiovascular disease in Han population in Ji Lin province. Because R611C position are in the uncoding region of LRP6 gene,it can not directly affect the expression of the relating protein. It may be in linkage disequilibrisum with other functional sites. But its mechanism needed further study.