Association of Polymorphism in Fatty Acid Desaturase Gene with the Risk of Type 2 Diabetes in Iranian Population

Mansouri, Vahid; Haghjooy Javanmard, Shaghayegh; Mahdavi, Manijeh; Tajedini, Mohammad Hasan

Association of Polymorphism in Fatty Acid Desaturase Gene with the Risk of Type 2 Diabetes in Iranian Population

Document Type : Original Article

Authors

¹ Department of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran

² Pediatric Inherited Diseases Research Center, Research Institute for Primordial Prevention of Noncommunicable Disease, Isfahan University of Medical Sciences, Isfahan, Iran

³ Applied Physiology Research Center, Isfahan University of Medical Sciences, Isfahan, Iran

Abstract

Background: The type 2 diabetes is one of the most common autoimmune diseases. Due to a key role in the metabolism of unsaturated fatty acids such as arachidonic acid, one of the most important precursors of immunity mediators, fatty acid desaturase (FADS) genes could have an important impact in the development of type 2 diabetes. Materials and Methods: This study aimed to determine the relationship between polymorphisms rs174537 in FADS1 gene and rs174575 in FADS2 gene with type 2 diabetes in Iranian population. After extracting genomic DNA, the locations of mutations and allele types were identified with high-resolution melting (HRM)-polymerase chain reaction method. Then, association between these mutations with metabolic syndrome, dyslipidemia, and type 2 diabetes was investigated using χ² correlation coefficients for variables and logistic regression. Results: The results showed that among 50 diabetic participants, 68% of patients have the mutant allele for rs174537 in FADS1 gene. This rate is 26% for rs174575 in FADS2 gene. Based on the results, it seems that participants having rs174537 mutant allele are more prone to become diabetic but it has a beneficial effect on total and low-density lipoprotein cholesterol and participants having rs174575 mutant are less prone to become diabetic, and also, it leads to higher triglycerides and body mass index (obesity). Conclusions: Detecting FADS1 and FADS2, gene polymorphisms using HRM can be an anticipating tool for making decision on initiating lifestyle modifications to prevent type 2 diabetes.

Keywords

References

1.	Guadarrama-López AL, Valdés-Ramos R, Martínez-Carrillo BE. Type 2 diabetes, PUFAs, and Vitamin D: Their relation to inflammation. J Immunol Res 2014;2014:860703.
2.	WHO. Global Status Report on Noncommunicable Diseases 2014. World Health Oraganzation; 2014. p. 298.
3.	Albert MA, Glynn RJ, Buring J, Ridker PM. C-reactive protein levels among women of various ethnic groups living in the United States (from the women's health study). Am J Cardiol 2004;93:1238-42. [PUBMED]
4.	Sergeant S, Hugenschmidt CE, Rudock ME, Ziegler JT, Ivester P, Ainsworth HC, et al. Differences in arachidonic acid levels and fatty acid desaturase (FADS) gene variants in African Americans and European Americans with diabetes or the metabolic syndrome. Br J Nutr 2012;107:547-55. [PUBMED]
5.	Warensjö E, Sundström J, Lind L, Vessby B. Factor analysis of fatty acids in serum lipids as a measure of dietary fat quality in relation to the metabolic syndrome in men. Am J Clin Nutr 2006;84:442-8.
6.	Huang T, Bhulaidok S, Cai Z, Xu T, Xu F, Wahlqvist ML, et al. Plasma phospholipids n-3 polyunsaturated fatty acid is associated with metabolic syndrome. Mol Nutr Food Res 2010;54:1628-35. [PUBMED]
7.	Huang T, Sun J, Chen Y, Xie H, Xu D, Huang J, et al. Genetic variants in desaturase gene, erythrocyte fatty acids, and risk for type 2 diabetes in Chinese Hans. Nutrition 2014;30:897-902. [PUBMED]
8.	Huang T, Wahlqvist ML, Xu T, Xu A, Zhang A, Li D, et al. Increased plasma n-3 polyunsaturated fatty acid is associated with improved insulin sensitivity in type 2 diabetes in China. Mol Nutr Food Res 2010;54 Suppl 1:S112-9.
9.	Lemaitre RN, King IB, Mozaffarian D, Sotoodehnia N, Rea TD, Kuller LH, et al. Plasma phospholipid trans fatty acids, fatal ischemic heart disease, and sudden cardiac death in older adults: The cardiovascular health study. Circulation 2006;114:209-15. [PUBMED]
10.	Shannon J, King IB, Moshofsky R, Lampe JW, Gao DL, Ray RM, et al. Erythrocyte fatty acids and breast cancer risk: A case-control study in Shanghai, China. Am J Clin Nutr 2007;85:1090-7. [PUBMED]
11.	Innis SM. Perinatal biochemistry and physiology of long-chain polyunsaturated fatty acids. J Pediatr 2003;143:S1-8.
12.	Innis SM. Dietary omega 3 fatty acids and the developing brain. Brain Res 2008;1237:35-43. [PUBMED]
13.	Gillingham LG, Harding SV, Rideout TC, Yurkova N, Cunnane SC, Eck PK, et al. Dietary oils and FADS1-FADS2 genetic variants modulate [13C]α-linolenic acid metabolism and plasma fatty acid composition. Am J Clin Nutr 2013;97:195-207. [PUBMED]
14.	Li SW, Lin K, Ma P, Zhang ZL, Zhou YD, Lu SY, et al. FADS gene polymorphisms confer the risk of coronary artery disease in a Chinese Han population through the altered desaturase activities: Based on high-resolution melting analysis. PLoS One 2013;8:e55869. [PUBMED]
15.	Standl M, Lattka E, Stach B, Koletzko S, Bauer CP, von Berg A, et al. FADS1 FADS2 gene cluster, PUFA intake and blood lipids in children: Results from the GINIplus and LISAplus studies. PLoS One 2012;7:e37780. [PUBMED]
16.	Nakamura MT, Nara TY. Structure, function, and dietary regulation of delta6, delta5, and delta9 desaturases. Annu Rev Nutr 2004;24:345-76. [PUBMED]
17.	Beblo S, Reinhardt H, Demmelmair H, Muntau AC, Koletzko B. Effect of fish oil supplementation on fatty acid status, coordination, and fine motor skills in children with phenylketonuria. J Pediatr 2007;150:479-84. [PUBMED]
18.	Koletzko B, Cetin I, Brenna JT; Perinatal Lipid Intake Working Group, Child Health Foundation, Diabetic Pregnancy Study Group, et al. Dietary fat intakes for pregnant and lactating women. Br J Nutr 2007;98:873-7.
19.	Maes M, Smith R, Christophe A, Cosyns P, Desnyder R, Meltzer H, et al. Fatty acid composition in major depression: Decreased omega 3 fractions in cholesteryl esters and increased C20: 4 omega 6/C20:5 omega 3 ratio in cholesteryl esters and phospholipids. J Affect Disord 1996;38:35-46.
20.	Muskiet FA, Kemperman RF. Folate and long-chain polyunsaturated fatty acids in psychiatric disease. J Nutr Biochem 2006;17:717-27. [PUBMED]
21.	Nakada T, Kwee IL, Ellis WG. Membrane fatty acid composition shows delta-6-desaturase abnormalities in Alzheimer's disease. Neuroreport 1990;1:153-5. [PUBMED]
22.	Das UN. Essential fatty acid metabolism in patients with essential hypertension, diabetes mellitus and coronary heart disease. Prostaglandins Leukot Essent Fatty Acids 1995;52:387-91. [PUBMED]
23.	van Doormaal JJ, Muskiet FA, van Ballegooie E, Sluiter WJ, Doorenbos H. The plasma and erythrocyte fatty acid composition of poorly controlled, insulin-dependent (type I) diabetic patients and the effect of improved metabolic control. Clin Chim Acta 1984;144:203-12. [PUBMED]
24.	Vessby B. Dietary fat, fatty acid composition in plasma and the metabolic syndrome. Curr Opin Lipidol 2003;14:15-9. [PUBMED]
25.	Glew RH, Okolie H, Huang YS, Chuang LT, Suberu O, Crossey M, et al. Abnormalities in the fatty-acid composition of the serum phospholipids of stroke patients. J Natl Med Assoc 2004;96:826-32. [PUBMED]
26.	Leaf A. Prevention of sudden cardiac death by n-3 polyunsaturated fatty acids. Fundam Clin Pharmacol 2006;20:525-38. [PUBMED]
27.	Goldring MB, Berenbaum F. The regulation of chondrocyte function by proinflammatory mediators: Prostaglandins and nitric oxide. Clin Orthop Relat Res 2004;427 S37-46.
28.	Duchén K, Björkstén B. Polyunsaturated n-3 fatty acids and the development of atopic disease. Lipids 2001;36:1033-42.
29.	Kompauer I, Demmelmair H, Koletzko B, Bolte G, Linseisen J, Heinrich J, et al. Association of fatty acids in serum phospholipids with hay fever, specific and total immunoglobulin E. Br J Nutr 2005;93:529-35.
30.	Trak-Fellermeier MA, Brasche S, Winkler G, Koletzko B, Heinrich J. Food and fatty acid intake and atopic disease in adults. Eur Respir J 2004;23:575-82. [PUBMED]
31.	Lattka E, Illig T, Heinrich J, Koletzko B. Do FADS genotypes enhance our knowledge about fatty acid related phenotypes? Clin Nutr 2010;29:277-87. [PUBMED]
32.	Guillou H, Zadravec D, Martin PG, Jacobsson A. The key roles of elongases and desaturases in mammalian fatty acid metabolism: Insights from transgenic mice. Prog Lipid Res 2010;49:186-99. [PUBMED]
33.	Malerba G, Schaeffer L, Xumerle L, Klopp N, Trabetti E, Biscuola M, et al. SNPs of the FADS gene cluster are associated with polyunsaturated fatty acids in a cohort of patients with cardiovascular disease. Lipids 2008;43:289-99. [PUBMED]
34.	Martinelli N, Girelli D, Malerba G, Guarini P, Illig T, Trabetti E, et al. FADS genotypes and desaturase activity estimated by the ratio of arachidonic acid to linoleic acid are associated with inflammation and coronary artery disease. Am J Clin Nutr 2008;88:941-9. [PUBMED]
35.	Rzehak P, Heinrich J, Klopp N, Schaeffer L, Hoff S, Wolfram G, et al. Evidence for an association between genetic variants of the fatty acid desaturase 1 fatty acid desaturase 2 (FADS1 FADS2) gene cluster and the fatty acid composition of erythrocyte membranes. Br J Nutr 2009;101:20-6. [PUBMED]
36.	Schaeffer L, Gohlke H, Müller M, Heid IM, Palmer LJ, Kompauer I, et al. Common genetic variants of the FADS1 FADS2 gene cluster and their reconstructed haplotypes are associated with the fatty acid composition in phospholipids. Hum Mol Genet 2006;15:1745-56.
37.	Xie L, Innis SM. Genetic variants of the FADS1 FADS2 gene cluster are associated with altered (n-6) and (n-3) essential fatty acids in plasma and erythrocyte phospholipids in women during pregnancy and in breast milk during lactation. J Nutr 2008;138:2222-8. [PUBMED]
38.	Kröger J, Schulze MB. Recent insights into the relation of Δ5 desaturase and Δ6 desaturase activity to the development of type 2 diabetes. Curr Opin Lipidol 2012;23:4-10.
39.	Warensjö E, Rosell M, Hellenius ML, Vessby B, De Faire U, Risérus U, et al. Associations between estimated fatty acid desaturase activities in serum lipids and adipose tissue in humans: Links to obesity and insulin resistance. Lipids Health Dis 2009;8:37.
40.	Vessby B, Gustafsson IB, Tengblad S, Boberg M, Andersson A. Desaturation and elongation of fatty acids and insulin action. Ann N Y Acad Sci 2002;967:183-95. [PUBMED]
41.	Dupuis J, Langenberg C, Prokopenko I, Saxena R, Soranzo N, Jackson AU, et al. New genetic loci implicated in fasting glucose homeostasis and their impact on type 2 diabetes risk. Nat Genet 2010;42:105-16. [PUBMED]
42.	Florez JC, Jablonski KA, McAteer JB, Franks PW, Mason CC, Mather K, et al. Effects of genetic variants previously associated with fasting glucose and insulin in the diabetes prevention program. PLoS One 2012;7:e44424. [PUBMED]
43.	Ingelsson E, Langenberg C, Hivert MF, Prokopenko I, Lyssenko V, Dupuis J, et al. Detailed physiologic characterization reveals diverse mechanisms for novel genetic loci regulating glucose and insulin metabolism in humans. Diabetes 2010;59:1266-75. [PUBMED]
44.	Kim OY, Lim HH, Yang LI, Chae JS, Lee JH. Fatty acid desaturase (FADS) gene polymorphisms and insulin resistance in association with serum phospholipid polyunsaturated fatty acid composition in healthy Korean men: Cross-sectional study. Nutr Metab (Lond) 2011;8:24.
45.	Lu Y, Feskens EJ, Dollé ME, Imholz S, Verschuren WM, Müller M, et al. Dietary n-3 and n-6 polyunsaturated fatty acid intake interacts with FADS1 genetic variation to affect total and HDL-cholesterol concentrations in the doetinchem cohort study. Am J Clin Nutr 2010;92:258-65.
46.	Sjögren P, Sierra-Johnson J, Gertow K, Rosell M, Vessby B, de Faire U, et al. Fatty acid desaturases in human adipose tissue: Relationships between gene expression, desaturation indexes and insulin resistance. Diabetologia 2008;51:328-35.

Advanced Biomedical Research