Abstract
Polyunsaturated fatty acids (PUFA) correlate with risk of dyslipidemia and cardiovascular diseases. Fatty acid desaturase (FADS) single nucleotide polymorphisms (SNPs) modulate circulating PUFA concentrations. This study examined influence of FADS1 and FADS2 genetic variants on desaturase activities and blood lipid concentrations in type 2 diabetes patients, and further assessed their interrelationships. Selected SNPs (FADS1: rs174547, rs174548, rs174550; FADS2: rs174575, rs174576, rs174583, rs498793 and rs2727270) were genotyped in 820 type 2 diabetes patients and compared with those reported in the HapMap. Patient subgroups (n = 176) without taking lipid-lowering medicine were studied to assess influence of tag SNPs including rs174547, rs174575, rs498793 and rs2727270 on delta-5 desaturase (D5D: 20:4 (n-6)/20:3 (n-6)) and delta-6 desaturase (D6D:18:3 (n-6)/18:2 (n-6)) activities, and blood lipids. FADS1 rs174547 TT/TC/CC and FADS2 rs2727270 CC/CT/TT were significantly (p for trend < 0.05) associated with reduced HDL-C, D5D and D6D activities. Upon adjustment for confounders, D5D (p = 0.006) correlated significantly and D6D marginally (p = 0.07) correlated with increased HDL-C levels, whereas rs174547 and rs2727270 polymorphisms were not associated. D6D andD5D activities may play a role in modulating HDL-C levels in type 2 diabetes. Future studies with larger sample sizes are needed to investigate how FADS genetic variations interact with desaturase activities or PUFAs in the metabolism of lipoproteins in diabetic patients.
Highlights
Type 2 diabetes mellitus is a well-established risk factor for cardiovascular diseases, and is frequently accompanied by metabolic abnormalities including hypertriglyceridemia, high low-density lipoprotein cholesterol (LDL-C) or low high-density lipoprotein cholesterol (HDL-C) [1,2]
Recent gene and genome-wide association studies (GWAS) have shown that polymorphisms in the Fatty acid desaturase (FADS) gene cluster have an important impact on lipid profiles and glucose homeostasis, [8,9,10] and they play a role in modifying risk of metabolic diseases
This study found Fatty acid desaturase 1 (FADS1) rs174547 and fatty acid desaturase 2 (FADS2) rs2727270 genotypes were significantly correlated with decreased delta-5 desaturase (D5D) and delta-6 desaturase (D6D) activities and decreased HDL-C concentrations in patients with type 2 diabetes
Summary
Type 2 diabetes mellitus is a well-established risk factor for cardiovascular diseases, and is frequently accompanied by metabolic abnormalities including hypertriglyceridemia, high low-density lipoprotein cholesterol (LDL-C) or low high-density lipoprotein cholesterol (HDL-C) [1,2]. Adults with diabetes have heart disease-related mortality rates that are two to four times higher than those without diabetes [4]. It is, important to study risk factors for the development of dyslipidemia in patients with type 2 diabetes. Recent gene and genome-wide association studies (GWAS) have shown that polymorphisms in the FADS gene cluster have an important impact on lipid profiles and glucose homeostasis, [8,9,10] and they play a role in modifying risk of metabolic diseases
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