An association analysis between ApoA1 polymorphisms and the high-density lipoprotein (HDL) cholesterol level and myocardial infarction (MI) in Japanese

Abstract

Association studies were performed to confirm the effect of polymorphisms in apolipoprotein A1 (ApoA1) on the high-density lipoprotein cholesterol (HDL-C) level and the incidence of myocardial infarction (MI). A sequence analysis identified nine polymorphisms in ApoA1. After considering linkage disequilibrium, four polymorphisms in ApoA1and four polymorphisms in the 5¢-flanking regions and 3¢-flanking regions from the JSNP database were determined in 1,880 subjects recruited from the Suita study, which represents the general population in Japan. Of the eight polymorphisms tested, the ApoA1 T84C polymorphism had the greatest effect on the levels of HDL-C (P=0.0005, P c =0.0040 corrected by the Bonferroni method) and triglyceride (P<0.0001, P c =0.0008). The ApoA1 MspI polymorphism was not associated with HDL-C or triglyceride levels. We confirmed that the ApoA1 T84C polymorphism was associated with the HDL-C level but not the triglyceride level in patients with MI (n=637). Moreover, this polymorphism was associated with the incidence of MI in male subjects (P=0.0326). A logistic analysis indicated that the frequency of MI in the CC genotype was lower than that in the CT+TT genotype (P=0.0145, OR=0.4955, 95% CI: 0.2746-0.8525). The ApoA1 T84C polymorphism is an important marker for the HDL-C level and may be a new risk marker for MI in Japanese.

The APOA1/C3/A4/A5 gene cluster, lipid metabolism and cardiovascular disease risk

“…In brief, the APOA1 (À75G > A) polymorphism has been found to be associated by some with elevated APOA1 and HDLcholesterol concentrations [39][40][41][42][43], suggesting a protective effect for the minor allele. However, these findings are far from being consistent and they appear to be significantly modified by environmental factors [44]. The variants À482C > T and À455T > C at the insulin response element in the promoter region of the APOC3 gene, which are in strong LD with the most studied variant APOC3-SstI (3238C > G) [23 ,45], primarily affect plasma triglyceride concentrations [46,47]; and carriers of the minor allele may have an increased risk of coronary artery disease (CAD) [46].…”

ApoA1 and ApoA1-specific self-antibodies in cardiovascular disease

“…Plasma HDL cholesterol and ApoA1 levels are associated with lower CVD risk, especially MI risk. 23,24 However, atherosclerosis-related oxidative stress and inflammation lead to oxidation and other modifications of mature ApoA1, a phenomenon that can switch atheroprorective properties of native apoA1 to proatherogenic properties of modified ApoA1. 25 ApoA1 modification could induce formation of ApoA1-specific IgG antibodies that exhibit pro-inflammatory properties.…”

Assessment of MEF2A Mutations in Myocardial Infarction in Japanese Patients

“…[12][13][14] We excluded young subjects from the control group, because they might develop MI in their 50 s and 60 s. The MI group consisted of 379 randomly selected inpatients and outpatients with documented MI who were admitted to the Division of Cardiology at the National Cardiovascular Center between May 2001 and April 2003 (MI group). 15 The characteristics of the study population are shown in Table 1. All subjects gave written informed consent and the present study was approved by the Ethics Committee of the National Cardiovascular Center and by the Committee on Genetic Analysis and Gene Therapy of the National Cardiovascular Center.…”