Effect of ABCA1 variant on atherogenic dyslipidaemia in patients with Type 2 diabetes treated with rosiglitazone

Abstract

AIMS: To investigate the effect of two common ATP-binding cassette transporter 1 (ABCA1) polymorphisms (rs4149263 and rs2020927) on atherogenic dyslipidaemia in Korean Type 2 diabetic patients who were treated with rosiglitazone.

PATIENTS AND METHODS: Two hundred and fifty-six patients with Type 2 diabetes who had never previously received peroxisome proliferator-activated receptor gamma (PPAR-gamma) agonists or lipid-lowering treatment were treated with 4 mg of rosiglitazone daily for 12 weeks without any adjustment to their glucose-lowering regimen. The primary outcome was the change in atherogenic index of plasma (AIP), calculated as log [triglyceride (mmol/l)/high-density lipoprotein cholesterol (mmol/l)], before and after rosiglitazone treatment. The effect of rosiglitazone on the change in AIP was compared across the ABCA1 single nucleotide polymorphisms (SNPs) rs41429263 and rs2020927.

RESULTS: Before adjustment, the change in AIP at 12 weeks was significantly different across the rs4149263 genotypes [median (interquartile range): -0.05 (-0.21, 0.09) for TT; 0.02 (-0.09, 0.17) for TC; and 0.11 (0.03, 0.25) for CC; P = 0.003], but not across the rs2020927 [-0.04 (-0.18, 0.10) for TT; 0.03 (-0.17, 0.15) for TC; and -0.03 (-0.13, 0.10) for CC; P = 0.401]. After controlling for age, gender and duration of diabetes, the presence of the C-allele was significantly associated with an increase in AIP by 0.13 [95% confidence interval (CI), 0.04-0.21; P = 0.003]. This association did not change significantly when body mass index and pretreatment metabolic parameters were additionally controlled for (the change in AIP: 0.14; 95% CI, 0.04-0.24; P = 0.007).

CONCLUSIONS: The ABCA1 SNP rs4149263 may be associated with the change in atherogenic lipid profile in Type 2 diabetes treated with rosiglitazone.