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Genetic variants in FADS1 and ELOVL2 increase level of arachidonic acid and the risk of Alzheimer's disease in the Tunisian population.

Abstract

Polyunsaturated fatty acids (PUFAs) are closely related to various physiological conditions. In several age-related diseases including Alzheimer's disease (AD) altered PUFAs metabolism has been reported. However, the mechanism behind PUFAs impairment and AD developpement remains unclear. In humans, PUFAs biosynthesis requires delta-5 desaturase (D5D), delta-6 desaturase (D6D) and elongase 2 activities; which are encoded by fatty acid desaturase 1 (FADS1), fatty acid desaturase 2 (FADS2), and elongation of very-long-chain fatty acids-like 2 (ELOVL2) genes, respectively. In the present work, we aim to assess whether genetic variants in FADS1, FADS2 and ELOVL2 genes influence plasma and erythrocyte PUFA composition and AD risk. A case-control study was carried out in 113 AD patients and 161 healthy controls.Rs174556, rs174617, and rs3756963 of FADS1, FADS2, and ELOVL2 genes, respectively were genotyped using PCR-RFLP. PUFA levels were quantified using Gas Chromatography. Genotype distributions of rs174556 (FADS1) and rs3756963 (ELOVL2) were different between case and control groups. The genotype TT of rs174556 and rs3756963 single nucleotide polymorphism (SNP) increases significantly the risk of AD in our population. PUFA analysis showed higher plasma and erythrocyte arachidonic acid (AA) level in patients with AD, whereas only plasma docosahexaenoic acid (DHA) was significantly decreased in AD patients. The indexes AA/Dihomo-gamma-linolenic acid (DGLA) and C24:4n-6/Adrenic acid (AdA) were both higher in the AD group. Interestingly, patients with TT genotype of rs174556 presented higher AA level and AA/DGLA index in both plasma and erythrocyte. In addition, higher AA and AA/DGLA index were observed in erythrocyte of TT genotype ofrs3756963 carrier's patients. Along with, positive correlation between AA/DGLA index, age or Gamma-linolenic acid (GLA)/ Linoleic acid (LA) index was seen in erythrocyte and /or plasma of AD patients. After adjustment for confounding factors, the genotype TT of rs174556, erythrocyte AA and AA/DGLA index were found to be predictive risk factors for AD while plasma DHA was found associated with lower AD risk. Both rs174556 and rs3756963 influence AD risk in the Tunisian population and they are likely associated with high AA level. The combination of the two variants increases further the susceptibility to AD. We suggest that FADS1 and ELOVL2 variants could likely regulate the efficiency of AA biosynthesis which could be at the origin of inflammatory derivate.

Authors+Show Affiliations

Biochemistry Laboratory, LR12ES05 LR-NAFS 'Nutrition - Functional Food & Health' Faculty of Medicine Monastir, Tunisia.Biochemistry Laboratory, LR12ES05 LR-NAFS 'Nutrition - Functional Food & Health' Faculty of Medicine Monastir, Tunisia.Biochemistry Laboratory, LR12ES05 LR-NAFS 'Nutrition - Functional Food & Health' Faculty of Medicine Monastir, Tunisia.Biochemistry Laboratory, LR12ES05 LR-NAFS 'Nutrition - Functional Food & Health' Faculty of Medicine Monastir, Tunisia; Department of Internal Medicine Bourguiba Monastir, Geriatric unit, Monastir Tunisia.Department of Internal Medicine, Tahar Sfar Hospital, Mahdia. Tunisia.Department of neurology, Regional hospital of Kairouan. Tunisia.Biochemistry Laboratory, LR12ES05 LR-NAFS 'Nutrition - Functional Food & Health' Faculty of Medicine Monastir, Tunisia.Biochemistry Laboratory, LR12ES05 LR-NAFS 'Nutrition - Functional Food & Health' Faculty of Medicine Monastir, Tunisia; Biochemistry Laboratory, Faculty of Medicine Sousse. Tunisia. Electronic address: zarroukaamira@gmail.com.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

32682282

Citation

Hammouda, Souha, et al. "Genetic Variants in FADS1 and ELOVL2 Increase Level of Arachidonic Acid and the Risk of Alzheimer's Disease in the Tunisian Population." Prostaglandins, Leukotrienes, and Essential Fatty Acids, vol. 160, 2020, p. 102159.
Hammouda S, Ghzaiel I, Khamlaoui W, et al. Genetic variants in FADS1 and ELOVL2 increase level of arachidonic acid and the risk of Alzheimer's disease in the Tunisian population. Prostaglandins Leukot Essent Fatty Acids. 2020;160:102159.
Hammouda, S., Ghzaiel, I., Khamlaoui, W., Hammami, S., Mhenni, S. Y., Samet, S., Hammami, M., & Zarrouk, A. (2020). Genetic variants in FADS1 and ELOVL2 increase level of arachidonic acid and the risk of Alzheimer's disease in the Tunisian population. Prostaglandins, Leukotrienes, and Essential Fatty Acids, 160, 102159. https://doi.org/10.1016/j.plefa.2020.102159
Hammouda S, et al. Genetic Variants in FADS1 and ELOVL2 Increase Level of Arachidonic Acid and the Risk of Alzheimer's Disease in the Tunisian Population. Prostaglandins Leukot Essent Fatty Acids. 2020;160:102159. PubMed PMID: 32682282.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Genetic variants in FADS1 and ELOVL2 increase level of arachidonic acid and the risk of Alzheimer's disease in the Tunisian population. AU - Hammouda,Souha, AU - Ghzaiel,Imen, AU - Khamlaoui,Wided, AU - Hammami,Sonia, AU - Mhenni,Samia Younes, AU - Samet,Slim, AU - Hammami,Mohamed, AU - Zarrouk,Amira, Y1 - 2020/07/04/ PY - 2020/04/22/received PY - 2020/06/15/revised PY - 2020/07/02/accepted PY - 2020/7/19/pubmed PY - 2020/7/19/medline PY - 2020/7/19/entrez KW - Alzheimer's disease (AD) KW - Arachidonic acid (AA) KW - Elongation of very-long-chain fatty acids-like 2 (ELOVL2) KW - Fatty acid desaturase 1 (FADS1) KW - Fatty acid desaturase 2 (FADS2) KW - Single nucleotide polymorphism (SNP) KW - polyunsaturated fatty acids (PUFAs) SP - 102159 EP - 102159 JF - Prostaglandins, leukotrienes, and essential fatty acids JO - Prostaglandins Leukot. Essent. Fatty Acids VL - 160 N2 - Polyunsaturated fatty acids (PUFAs) are closely related to various physiological conditions. In several age-related diseases including Alzheimer's disease (AD) altered PUFAs metabolism has been reported. However, the mechanism behind PUFAs impairment and AD developpement remains unclear. In humans, PUFAs biosynthesis requires delta-5 desaturase (D5D), delta-6 desaturase (D6D) and elongase 2 activities; which are encoded by fatty acid desaturase 1 (FADS1), fatty acid desaturase 2 (FADS2), and elongation of very-long-chain fatty acids-like 2 (ELOVL2) genes, respectively. In the present work, we aim to assess whether genetic variants in FADS1, FADS2 and ELOVL2 genes influence plasma and erythrocyte PUFA composition and AD risk. A case-control study was carried out in 113 AD patients and 161 healthy controls.Rs174556, rs174617, and rs3756963 of FADS1, FADS2, and ELOVL2 genes, respectively were genotyped using PCR-RFLP. PUFA levels were quantified using Gas Chromatography. Genotype distributions of rs174556 (FADS1) and rs3756963 (ELOVL2) were different between case and control groups. The genotype TT of rs174556 and rs3756963 single nucleotide polymorphism (SNP) increases significantly the risk of AD in our population. PUFA analysis showed higher plasma and erythrocyte arachidonic acid (AA) level in patients with AD, whereas only plasma docosahexaenoic acid (DHA) was significantly decreased in AD patients. The indexes AA/Dihomo-gamma-linolenic acid (DGLA) and C24:4n-6/Adrenic acid (AdA) were both higher in the AD group. Interestingly, patients with TT genotype of rs174556 presented higher AA level and AA/DGLA index in both plasma and erythrocyte. In addition, higher AA and AA/DGLA index were observed in erythrocyte of TT genotype ofrs3756963 carrier's patients. Along with, positive correlation between AA/DGLA index, age or Gamma-linolenic acid (GLA)/ Linoleic acid (LA) index was seen in erythrocyte and /or plasma of AD patients. After adjustment for confounding factors, the genotype TT of rs174556, erythrocyte AA and AA/DGLA index were found to be predictive risk factors for AD while plasma DHA was found associated with lower AD risk. Both rs174556 and rs3756963 influence AD risk in the Tunisian population and they are likely associated with high AA level. The combination of the two variants increases further the susceptibility to AD. We suggest that FADS1 and ELOVL2 variants could likely regulate the efficiency of AA biosynthesis which could be at the origin of inflammatory derivate. SN - 1532-2823 UR - https://www.unboundmedicine.com/medline/citation/32682282/Genetic_variants_in_FADS1_and_ELOVL2_increase_level_of_arachidonic_acid_and_the_risk_of_Alzheimer's_disease_in_the_Tunisian_population_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0952-3278(20)30117-4 DB - PRIME DP - Unbound Medicine ER -
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