Association between two common polymorphisms (single nucleotide polymorphism -250G/A and -514C/T) of the hepatic lipase gene and coronary artery disease in type 2 diabetic patients

Abstract

Background: Variations in the hepatic lipase (HL) gene are the potential candidate for coronary artery disease (CAD) especially in type 2 diabetes mellitus (T2DM) in diverse populations. We assessed the association of -514C/T and -250G/A polymorphisms in HL (LIPC) gene with CAD risk in Iranian population with type 2 diabetes.

Materials and methods: We evaluated 322 type 2 diabetic patients, 166 patients with normal angiograms as controls and 156 patients those identified with CAD undergoing their first coronary angiography as CAD cases. Genotyping of -514C/T and -250G/A polymorphisms in the promoter of the LIPC gene were studied by polymerase chain reaction (PCR)-restriction fragment length polymorphism technique.

Results: Genotype distributions in CAD cases (73.7%, 20.5%, and 5.8% for -250G/A) and (62.2%, 32.7%, and 5.1% for -514C/T) were significantly different from those in controls (60.8%, 37.4%, and 1.8% for -250G/A) and (51.2%, 48.2%, and 0.6% for -514C/T). CAD cases had lower A-allele frequency than controls (0.131 vs. 0.196, P = 0.028). The odds ratio for the presence of -250 (GG + GA) genotype and A allele in CAD cases were 2.206 (95% confidence interval [CI] =1.33-3.65, P = 0.002) and 1.609 (95% CI = 1.051 -2.463, P = 0.029) respectively. Haplotype analysis demonstrated a significant association between especially LIPC double mutant (-250 A/-514 T) haplotype and presence of CAD.

Conclusion: Our findings indicated that -250 G/A polymorphism rather than -514 C/T polymorphism of LIPC gene is more associated with the increased risk of CAD particularly in women with T2DM.

Keywords: LIPC gene; Type 2 diabetes; coronary artery disease; polymorphisms.

Figure 1

Product of polymerase chain reaction-restriction fragment length polymorphism for −250G/A genotypes of LIPC gene on the 2% agarose gel. Lane 1 is DNA size marker 100 bp, lane 2–5 and 8–10 are related to the GG genotype, lane 6, 7 are related to the GA genotype and lane 11 is related to the AA genotype

Figure 2

Product of polymerase chain reaction-restriction fragment length polymorphism for −514C/T genotypes of LIPC gene on the 2% agarose gel. Lane 1 is DNA size marker 100 bp, Lane 2 is related to the non-template control, lane 3–6 and 8,10,11,13-19, and 21 are related to the CC genotype, lane 21 is related to the CT genotype and lanes 7,9 and 12 are related to the TT genotype