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

The purpose of the study is to evaluate the associations between polymorphisms of the human SA (SAH) gene, an acyl-CoA synthetase gene, with dyslipidemia and phenotypes of the insulin resistance syndrome in postmenopausal women. 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.-451G>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. There were significant differences in genetic distribution of the SAH gene promoter I/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 II 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. 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.