MedWire News: Common genetic polymorphisms in the adenosine triphosphate–binding cassette transporter A1 gene (ABCA1) are associated with variation in high-density lipoprotein (HDL) cholesterol and risk for coronary heart disease (CHD) in patients with Type 2 diabetes mellitus, report researchers.
“Patients with Type 2 diabetes mellitus have a high coronary risk partly because of low levels of HDL cholesterol,” explain Frédéric Fumeron (INSERM, Paris, France) and team.
“Many common genetic variations in ABCA1 have been reported to be associated with variations in serum lipid levels, HDL cholesterol levels in particular, and may also be associated with coronary artery disease risk.”
The researchers recruited a cohort of Type 2 diabetics to assess links between genotypes of five single nucleotide polymorphisms (SNPs) of ABCA1 (+69C/T, +378G/C, R219K, I883M, and R1587K) and variation in HDL cholesterol concentration and coronary risk.
The cohort consisted of the 3129 French participants of the DIABHYCAR (Noninsulin Dependent Diabetes, Hypertension, Microalbuminuria or Proteinuria, Cardiovascular Events, and Ramipril) study, who took part in a randomized controlled trial to assess the effectiveness of low doses of the antihypertensive drug ramipril versus placebo. Patients were aged a minimum of 50 years and were followed-up for an average of 4 years at 6-monthly intervals.
At baseline, 482 participants had CHD (prevalent) and an additional 223 individuals developed CHD (incident) during the study period. CHD was defined as either a history or occurrence of myocardial infarction and/or angina pectoris.
The authors found that carriers of the C allele of +378G/C had significantly lower, and carriers of the M allele of I883M had significantly higher levels of HDL cholesterol than noncarriers.
No connection was observed between genotypes of these polymorphisms and incident CHD during the study period.
However, the frequency of the K allele of R219K was significantly lower in patients with prevalent CHD at baseline, with CHD patients 20% less likely to be carriers of the K allele than participants without CHD.
In addition, the K allele of R1587K was present at a higher frequency in patients with angina pectoris at baseline, with carriers 27% more likely to have prevalent angina pectoris than noncarriers.
Finally, homozygotes for the T allele of C69T were 72% less likely to have had prior myocardial infarction at the start of the study than those with alternate genotypes. Of note, the associations of these polymorphisms with prevalent CHD were independent of HDL cholesterol level, which Fumeron et al believe indicates that “variation in ABCA1 associated with CHD exerts its effects principally by modifying reverse cholesterol transport in macrophages.”
These results are published in the journal Metabolism: Clinical and Experimental.
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