Multiple Common Variants In The LRP1 Gene With Circulating F â…§ Levels Confer Risk Of MI In A Chinese Han Population

Background and purpose:Low-density lipoprotein receptor-related protein (LRP1), a muLtifunctional endocytic receptor, plays a crucial role in celluLar uptake and degradation of clotting factor VIII (F VIII), which is recently reported to be an independent risk factor for arterial and venous thrombosis. We herein aimed to determine whether these variations confer susceptibility to myocardial infarction (MI) in a Chinese Han popuLation.Methods:By genotyping, the associations of 3 single nucleotide polymorphisms (SNPs),25 C＞G (rs35282763), D2080N (rs34577247 A>G) in the LRP1 gene and D1241E (rs 1800291 C＞G) in the F VIII gene with risk of MI were determined in a case-control of 347 pairs study. MuLtivariate logistic regression analysis was used to adjust effects of clinical covariates. The genotype-phenotype correlation was assessed in the subjects with MI and controls by chromogenic assay and enzyme-linked immunosorbent assay (ELISA) analysis.ResuLts:The resuLts indicated that 2080NN genotype was significantly associated with a reduced risk of MI when compared with 2080DD genotype (Odds ratios [OR]=0.252,95% confidence intervals [CI]:0.079-0.804, P=0.020). In addition, when compared with the combination of LRP1 2080DD/F VIIIDD, LRP1 2080 DN&NN/F VIII DD combination exhibited a significant relationship with a reduced risk of MI (P=0.017). Furthermore, the subjects carrying the 2080N allele showed lower F VIII activity levels than those with 2080D allele. LRP1 25CG (rs35282763) genotype distribution did not differ significantly between patients (25CC=206,25CG=212) and controls (25CC=191,25CG=126; P>0.05). The 25G allele was not associated with a reduced risk of MI (P>0.05). Further stratifications for age, sex, and other cardiovascuLar risk factors did not affect the negative findings.Conclusions:Our data showed that the variation at the LRP1 gene couLd contribute to a reduced risk of MI by moduLating F VIII levels. The presence of the G allele at the 25CG (rs35282763) polymorphism of the LRP1 was not associated with a reduced risk of MI, and no synergistic gene-environment interactions were detected. Genotyping for LRP1 25CG (rs35282763) polymorphism is not usefuL in assessing the individual risk of MI.