The combined effects of genetic variation in the SIRT1 gene and dietary intake of n-3 and n-6 polyunsaturated fatty acids on serum LDL-C and HDL-C levels: a population based study

BACKGROUND: Dyslipidemia due to high total cholesterol, LDL-cholesterol, triglycerides, or low HDL-cholesterol is an important risk factor for coronary heart disease (CHD). Both SIRT1 and PUFAs can influence the expression of genes for nuclear receptors and transcription factors related to lipid metabolism such as LXRα, LXRβ, PPARα, SREBP-1c. METHODS: A total of 707 Japanese males and 723 females were randomly selected from the participants who visited a medical center for routine medical check-ups. We analyzed the combined effects of the genotype/haplotype of the SIRT1 gene and dietary n-6/n-3 PUFA intake ratio on the determination of serum lipid levels. RESULTS: We found that the SIRT1 gene marked with haplotype 2 was associated with decreased serum LDL-cholesterol and increased HDL-cholesterol levels. In addition, the associations between the SIRT1 haplotype 2 and decreased LDL-C and increased HDL-C levels were only observed in the low n-6/n-3 PUFA intake ratio group, but not in the high n-6/n-3 PUFA intake ratio group. CONCLUSIONS: Our findings indicate that the combination of genetic variation in the SIRT1 gene and dietary n-6 and/or n-3 PUFA intake influence the determination of inter-individual variations of serum levels of LDL-C and HDL-C.