Abstract
Background ABCA1 genetic variation is known to play a role in HDL-C levels and various studies have also implicated ABCA1 variation in cardiovascular risk. The functional ABCA1/R230C variant is frequent in the Mexican population and has been consistently associated with low HDL-C concentrations. Although it has been associated with other cardiovascular risk factors such as obesity and type 2 diabetes mellitus, it is not known whether it is associated with coronary artery disease (CAD).AimThe purpose of the study was to analyze whether the ABCA1/R230C variant is associated with premature CAD in a case-control association study (GEA or Genetics of Atherosclerotic Disease), and to explore whether BMI modulates the effect of the C230 allele on other metabolic traits using a population-based design.ResultsThe C230 allele was significantly associated with both lower HDL-C levels and a lower risk of premature CAD as compared to controls (OR = 0.566; Padd = 1.499×10−5). In addition, BMI modulated the effect of R230C on body fat distribution, as the correlation between BMI and visceral to subcutaneous adipose tissue (a metric of the propensity to store fat viscerally as compared to subcutaneously) was negative in RR homozygous individuals, but positive in premenopausal women bearing the C230 allele, with a statistically significant interaction (P = 0.005). BMI-R230C interaction was also significant for triglyceride levels in women regardless of their menopausal status (P = 0.036).ConclusionThis is the first study assessing the effect of the R230C/ABCA1 variant in remature CAD. C230 was associated with both decreased HDL-C levels and a lower risk of premature CAD, and gender-specific BMI-R230C interactions were observed for different metabolic traits. These interactions may help explain inconsistencies in associations, and underscore the need to further analyze interactions of this functional and frequent variant with diet, exercise and other environmental factors.
Highlights
Epidemiological studies consistently demonstrate that a low plasma level of high density lipoprotein-cholesterol (HDL-C) is associated with increased risk of ischemic heart disease (IHD) [1]
C230 was associated with both decreased HDL-C levels and a lower risk of premature coronary artery disease (CAD), and gender-specific body mass index (BMI)-R230C interactions were observed for different metabolic traits
The purpose of the present study was to analyze whether the ATP-binding cassette A1 transporter (ABCA1)/R230C variant is associated with premature CAD and subclinical atherosclerosis in a case-control association study: GEA (Genetics of Atherosclerotic Disease)
Summary
Epidemiological studies consistently demonstrate that a low plasma level of high density lipoprotein-cholesterol (HDL-C) is associated with increased risk of ischemic heart disease (IHD) [1]. The 230C allele has a functional effect decreasing cholesterol efflux by approximately 30% in vitro and shows evidence of positive selection in Native Americans [13] This variant has been consistently associated with low HDL-C concentrations in various reports [13,14,15,16,17], and the sole presence of the C230 risk allele explains almost 4% of plasma HDL-C concentration variation, which is higher than all HDL-C variation associated with a single nucleotide polymorphism identified through genome-wide association studies in European and Asian populations [17]. It has been associated with other cardiovascular risk factors such as obesity and type 2 diabetes mellitus, it is not known whether it is associated with coronary artery disease (CAD)
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