| Summary: | 碩士 === 高雄醫學大學 === 醫學研究所 === 100 === Previous literatures have shown taht fatty acid desaturase (FADS) gene polymorphisms are associated with risk of cardiovascular disease (CVD). n-3 polyunsaturated fatty acids (PUFA) have been implicated to have beneficial effects on the reducing risks of CVD. FADS gene encodes rate-limiting enzymes which are required for PUFA synthesis. Evidence indicates lipid-lowering drugs and FADS genetic variations can affect fatty acid compositions by modifying desaturase activities. Additionally, n-3 PUFAs may also interact with FADS SNPs to affect lipid concentrations. Up to date, there have been very limited human studies availble. This study aimed to investigate the independent and combined effects of lipid-lowering drugs and FADS SNPs on the fatty acid desaturase activities. Further, we aimed to explore whether plasma n-3 PUFA status interacts with FADS SNPs to affect plasma lipid concentrations. A total of 874 type 2 diabetic patients were cross-sectionally recruited from the Diabetes Management through Integrated Delivery System (DMIDS) cohort. FADS SNPs (rs174546, rs174547, rs174556, rs102275, rs174570, rs1535, rs174579, rs174589, rs174602, rs174620, rs2072114, and rs526126) were genotypped and compared the frequencies to the HapMap database. The genotype frequencies were comparable to the CHD (Chinese in Metropolitan Denver, Colorado, USA) population. The association between FADS variations and blood lipid concentrations were only found in those without use of lipid-lowering drug. There were total of 192 patients without use of lipid-lowering drug and age and sex-matched 192 patients with use of lipid-lowering drug were selected. Lipid-lowering drug use correlated with significantly higher Δ6 desaturase activities, but increases in Δ5 desaturase activities only reached a marginal significance (p=0.059). Stratified by lipid-lowering drug use,Δ6 desaturase activities among FADS polymorphisms (rs174546, rs174547, rs174556, rs102275, rs174570, rs1535, rs174579, rs174589, rs174602, and rs2072114) genotypes were significantly different in user as well as in non-user.Δ5 desaturase activities were only different in rs174546, rs174547, rs174556, rs102275, rs174570, and rs1535 genotypes in user as well as in non-user. However, there was no significant interaction between lipid-lowering drug use and FADS SNPs. In low ALA/LA, n-3/n-6 PUFA, and n-3 LCPUFA status, HDL concentrations were significantly different among FADS SNP genotypes (rs174547, rs174556, rs102275, rs174570, rs1535, rs174602, and rs2072114). In terms of LDL, only low ALA/LA status, LDL concentrations were significantly different among genotypes of SNP rs174546, rs174556, rs102275, rs174570, rs174602, and rs2072114. However, in the group of high ALA/LA, n-3/n-6 PUFA, and n-3 LCPUFA status in plasma, HDL and LDL concentrations did not differ.
In conclusion, HDL and LDL concentrations may be modified by FADS genetic variations only in those without use of lipid-lowering drug. Lipid-lowering drug significantly associated with elevated Δ6 desaturase activities. Δ5/Δ6 desaturase activities may also be modified by some FADS SNPs. In patients with low n-3 PUFA status, HDL and LDL concentrations were associated with FADS SNP genotypes.
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