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Fatty acid desaturase 2 (FADS 2) rs174575 (C/G) polymorphism, circulating lipid levels and susceptibility to type-2 diabetes mellitus.

ABSTRACT: Several factors influence an individual's susceptibility in inter-individual lipid changes and its role in the onset of type-2 diabetes mellitus (T2DM). Considering the above fact, the present investigation focuses on determining the association between fatty acid desaturase 2 (FADS2) rs174575 (C/G) polymorphism, circulating lipid levels and susceptibility to type-2 diabetes mellitus. As per the inclusion and exclusion criteria a total of 429 subjects (non-diabetic-216; diabetic-213) were recruited for the study. Glycemic and lipid profile status were assessed using commercially available kits. Based on the previous reports SNP rs174575 of fatty acid desaturase gene (FADS2) was selected and identified using the dbSNP database. The amplified products were sequenced by means of Sanger sequencing method. Lipid profile status and apolipoprotein levels revealed statistically significant difference between the groups. Three models were assessed namely, recessive model (CC vs CG + GG), dominant model (CC + CG vs GG) and additive model (CC vs CG vs GG). The recessive model, displayed a statistically significant variations between the circulating lipid levels in T2DM. The multivariate model with genotype (G allele carriers), triglyceride (TG) and insulin served as a predictive model. The study results potentiate the functional link between FADS2 gene polymorphism, lipid levels and type-2 diabetes mellitus.

SUBMITTER: Shetty SS

PROVIDER: S-EPMC8222307 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:ObjectiveMaternal abnormal fatty acid desaturation has previously been linked to gestational diabetes mellitus (GDM). However, few studies have investigated this relationship longitudinally throughout pregnancy. In this study, we investigated the relationship between GDM and desaturase activities across the pregnancy trimesters.MethodsA total of 661 women (GDM = 189, non-GDM = 472) were selected from the Complex Lipids in Mothers and Babies (CLIMB) cohort study. Clinical information and maternal serum were collected at 11-14, 22-28, and 32-34 weeks of gestation. Totally, 20 serum fatty acids were quantified using gas chromatography-mass spectrometry (GC-MS) analysis at each timepoint. Polyunsaturated fatty acid (PUFA) product-to-precursor ratios were used to estimate desaturase and elongase activities including delta-5 desaturase, delta-6 desaturase, stearoyl-CoA desaturase, and elongase.ResultsAfter adjusting for major potential confounders including maternal age, BMI, primiparity, smoking, and alcohol consumption, we observed a significant increase in the levels of γ-linolenic acid (GLA) and eicosatrienoic acid (DGLA) in the first trimester of women with GDM, whereas GLA and DGLA were reduced in the third trimester, when compared to the non-GDM group. Arachidonic acid (AA) showed an upward trend in the GDM group throughout pregnancy. Estimated delta-6 desaturase and delta-5 desaturase activity were elevated in the first trimester (OR = 1.40, 95% CI 1.03-1.91; OR = 0.56, 95% CI 0.32-0.96) but attenuated in the third trimester (OR = 0.78, 95% CI 0.58-1.07; OR = 2.64, 95% CI 1.46-4.78) in GDM pregnancies, respective to controls. Estimated delta-9-18 desaturase activity (OR = 3.70, 95% CI 1.49-9.19) was increased in women with GDM in later pregnancy.ConclusionsOur study highlights the potential importance of fatty acid desaturase activities, particularly estimated delta-5 desaturase and delta-9-18 desaturase in the pathophysiology of GDM. These findings may have applications for the early diagnosis and management of GDM.

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Fatty acid desaturase 2 (FADS 2) rs174575 (C/G) polymorphism, circulating lipid levels and susceptibility to type-2 diabetes mellitus.

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