The ABCA1 Gene R230C Variant Is Associated with Decreased Risk of Premature Coronary Artery Disease: The Genetics of Atherosclerotic Disease (GEA) Study

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.

Fatty liver largely explains associations of subclinical hypothyroidism with insulin resistance, metabolic syndrome, and subclinical coronary atherosclerosis

“…The GEA study was designed to examine the genomic bases of CHD and assess relationships between traditional and emerging risk factors with clinical and subclinical atherosclerotic vascular diseases in an adult Mexican population (17). Briefly, a convenience sample of 1000 CHD patients and 1500 control subjects aged 35-70 years is being recruited from residents in Mexico City.…”

Low concentrations of phospholipids and plasma HDL cholesterol subclasses in asymptomatic subjects with high coronary calcium scores

“…The primary aim of the GEA Study was to investigate genetic factors associated with premature CAD, subclinical atherosclerosis and other coronary risk factors, in the Mexican population. The selection of patients from the GEA Study has been described previously [26]. All participants provided written informed consent, and the study complied with the Declaration of Helsinki and was approved by the Ethics Committee of the Instituto Nacional de Cardiología ''Ignacio Ch avez'' (INCICH).…”

PHACTR1 Gene Polymorphism Is Associated with Increased Risk of Developing Premature Coronary Artery Disease in Mexican Population

“…Patients and controls with previous history of liver, thyroid, malignant, or chronic renal disease, in addition those under corticosteroids treatment were excluded [22]. Physicians assessed all clinical variables and performed data collection.…”