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, LXRß, 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.

The combined effect of the T2DM susceptibility genes is an important risk factor for T2DM in non-obese Japanese: a population based case-control study.

BACKGROUND: Type 2 diabetes mellitus (T2DM) is a complex endocrine and metabolic disorder. Recently, several genome-wide association studies (GWAS) have identified many novel susceptibility loci for T2DM, and indicated that there are common genetic causes contributing to the susceptibility to T2DM in multiple populations worldwide. In addition, clinical and epidemiological studies have indicated that obesity is a major risk factor for T2DM. However, the prevalence of obesity varies among the various ethnic groups. We aimed to determine the combined effects of these susceptibility loci and obesity/overweight for development of T2DM in the Japanese. METHODS: Single nucleotide polymorphisms (SNPs) in or near 17 susceptibility loci for T2DM, identified through GWAS in Caucasian and Asian populations, were genotyped in 333 cases with T2DM and 417 control subjects. RESULTS: We confirmed that the cumulative number of risk alleles based on 17 susceptibility loci for T2DM was an important risk factor in the development of T2DM in Japanese population (P<0.0001), although the effect of each risk allele was relatively small. In addition, the significant association between an increased number of risk alleles and an increased risk of T2DM was observed in the non-obese group (P<0.0001 for trend), but not in the obese/overweight group (P=0.88 for trend). CONCLUSIONS: Our findings indicate that there is an etiological heterogeneity of T2DM between obese/overweight and non-obese subjects.

Val1483Ile polymorphism in the fatty acid synthase gene was associated with depressive symptoms under the influence of psychological stress.

BACKGROUND: To study the association between lipid-metabolism and depressive symptoms, genetic polymorphisms in serotonin transporter linked promoter region (5-HTTLPR) and fatty acid synthase gene (FASN) were investigated. METHOD: A cross-sectional study was conducted on 177 women (n = 166) and men (n = 15) recruited from workers in a hospital and nursing homes in Japan. Depressive symptoms were assessed by the Center for Epidemiologic Studies Depression (CES-D) scale and perceived psychological stress was measured using visual analogue scale (VAS). The genotypes of 5-HTTLPR (insertion/deletion; L/S), and FASN (Val1483Ile) were determined by the PCR methods. Linear regression analysis was performed, in which CES-D scores served as a dependent variable, and VAS scores, gene polymorphism, and confounders as independent variables. RESULTS: Under the influence of perceived stress, S/S carriers of the 5-HTTLPR gene showed significantly higher CES-D scores in comparison with L/L+L/S carriers (F = 8.2, standardised ß = 0.15, p < 0.05). Regression analysis also confirmed that CES-D scores in participants with Ile/Ile+Val/Ile genotypes of the FASN gene were significantly higher than those with Val/Val genotype (F = 8.4, standardised ß = 0.16, p<0.05). In relation to physical features, BMI among participants with S/S genotype of 5-HTTLPR was significantly lower compared with those with L/L+L/S genotypes. CONCLUSIONS: The Val1483Ile polymorphism in the FASN was associated with depressive symptoms under the influence of psychological stress. The S variant of 5-HTTLPR was related with less obese.