Human SA gene polymorphisms are associated with non-high-density lipoprotein cholesterol in postmenopausal women: A pilot study

Objective: The purpose of the study is to evaluate the associations between polymorphisms of the human SA (SAN) gene, an acyl-CoA synthetase gene. with dyslipidemia and phenotypes of the insulin resistance syndrome in postmenopausal women. Methods: One hundred and forty-two postmenopausal women were recruited for the study. Each subject received anthropometric and blood pressure measurements, fasting sampling for lipids, and a 75-g oral glucose tolerance test for insulin resistance. Genotypes of two polymorphisms in the promoter region (c.-962ins/del, c.-451 G > A), one missense variant (c.1077G > C, p.K359N) in exon 8, and one in intron 12 (A > G) of the SAH gene, were determined. Results: There were significant differences in genetic distribution of the SAH gene promoter 1/D polymorphism between the two groups of subjects by non-high-density lipoprotein cholesterol (non-HDL-C) levels (p=0.004). The subjects with the DD genotype was associated with high levels of non-HDL-C (>160 mg/dL) as compared with the ID or 11 genotypes (p=0.002). Furthermore, three haplotypes were constructed based on the promoter I/D and the exon 8 G/C polymorphisms. Homozygosity for SAH haplotype 3 was associated with increased adiposity, insulin resistance, and elevated levels of non-HDL-C in the post menopausal women. The subjects with haplotype 3 had double the risk to have higher non-HDL-C levels than those with haplotype 1. Conclusion: Our results suggest that the polymorphisms of the SAH gene are associated with non-HDL-C levels in postmenopausal women. Further studies with larger sample sizes or different populations are warranted to confirm our preliminary findings. Crown Copyright (c) 2008 Published by Elsevier Ireland Ltd. All rights reserved.