| Summary: | 碩士 === 高雄醫學大學 === 醫學研究所 === 101 === Cardiovascular disease (CVD) is considered one of the leading causes of death of type 2 diabetes. N-3 polyunsaturated fatty acids (PUFAs) have been shown to have beneficial effects on the risks of CVD. Fatty acid desaturase (FADS) gene encodes rate-limiting enzymes for PUFA synthesis, and its genetic variations have been shown to correlate with blood lipids concentrations and desaturase activities. Up to date, studies reporting these associations were mostly conducted in healthy populations. The aim of this study was to explore whether the FADS single nucleotide polymorphisms (SNPs) correlate with blood lipid concentrations and fatty acid desaturase activities in type 2 diabetes.
A total of 874 type 2 diabetic patients were cross-sectionally recruited from the Diabetes Management through Integrated Delivery System (DMIDS) cohort at 2008. We collected demographic information and analyzed clinical biomarkers. Nine FADS1/2 SNPs (FADS1: rs174537, rs174548, rs174550; FADS2: rs174575, rs174576, rs174583, rs498793 and rs2727270) were genotyped. Of which, 173 patients without using lowering lipid drugs (statin and fibrate) and with complete plasma fatty acid measures were selected into further analyses. ANOVA-based models and independent t-test analysis were applied to compare the differences of lipid concentrations and desaturase activities among FADS genotypes.
In our diabetic subjects, frequencies of FADS1 SNP rs174548 and FADS2 SNPs rs174576, rs174583 and rs498793 genotypes were comparable to those reported of the HapMap CHD (Chinese in Metropolitan Denver, Colorado, USA) population. The HapMap dataset provides human genome information only based on healthy population. Future investigation is needed to increase sample size in DM groups as well as to recruit a group of healthy control in order to examine and further compare the frequencies of FADS SNP with those documented in the literature.
Further, we found that FADS2 SNP rs174576 can be the tag SNP of rs174548, rs174550, rs174583 and rs2727270. These SNPs were in strong linkage disequilibrium (LD) (r2≥0.8). Our results showed that tag SNP rs174576 C allele was associated with higher concentrations of HDL-C, while was not associated with total cholesterol、triglyceride、non-HDL-C、LDL-C concentrations. In addition, rs174576 C allele carriers had higher levels of fatty acid desaturase activities, including Δ5 (20:4n-6/20:3n-6) and Δ6 (18:3n-6/18:2n-6) desaturase activities and n-3 (20:5 n-3/18:3 n-3) and n-6 (20:4 n-6/18:2 n-6) pathway activities. Other SNPs (rs174548, rs174550, rs174583 and rs2727270) in the same LD block also showed similar results, indicating that this LD block was associated with plasma cholesterol concentrations (HDL-C) and desaturase activities.
In conclusion, tag SNP rs174576 C allele was associated with higher concentrations of HDL-C. Further, tag SNP rs174576 as well as highly-correlated SNP including rs174548、rs174550、rs174583 and rs2727270 also appeared to associate withΔ5/Δ6 desaturase and n-3/n-6 pathway activities. Whether the genetic variation and their subsequent modeification in blood lipids as well as desaturase activities would exert effects on diabetic complications development such as risks of cardiovascular diseases warrant further study.
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