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      Investigation of FADS Gene Cluster Single Nucleotide Polymorphisms in End-Stage Renal Disease Compared With Normal Controls

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          Abstract

          End-stage renal disease (ESRD) is a public health problem with a high burden. The condition is associated with abnormalities in lipid metabolism. The fatty acid desaturase (FADS) gene cluster includes three genes that are significantly correlated with a number of pathologic conditions related to abnormal lipid levels. In the current study, we genotyped rs174556, rs99780, and rs7115739 single nucleotide polymorphisms within the FADS cluster in a population of ESRD patients and healthy controls. The rs174556 of the FADS1 gene and rs99780 of the FADS2 gene were not associated with the risk of ESRD in any inheritance model. However, the rs7115739 of FADS3 was associated with the risk of ESRD in all models except for the recessive model. The T allele of this SNP was significantly less prevalent among cases compared with controls [odds ratio (OR) (95% CI) = 0.44 (0.25–0.77), P value = 0.004]. GT and TT genotypes has been shown to decrease the risk of ESRD in a codominant model [OR (95% CI) = 0.49 (0.26–0.92) and OR (95% CI) = 0.18 (0.02–1.6), respectively; P value = 0.019]. In the dominant model, GT + TT status was associated with lower risk of ESRD [OR (95% CI) = 0.45 (0.24–0.82), P value = 0.0078]. Assessment of association between this SNP and risk of ESRD in an overdominant model revealed that GT genotype decreases the risk of this condition [OR (95% CI) = 0.5 (0.27–0.94), P value = 0.029]. Taken together, the rs7115739 of FADS3 is suggested as a putative modulator of the risk of ESRD in the Iranian population.

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          Greenlandic Inuit show genetic signatures of diet and climate adaptation.

          The indigenous people of Greenland, the Inuit, have lived for a long time in the extreme conditions of the Arctic, including low annual temperatures, and with a specialized diet rich in protein and fatty acids, particularly omega-3 polyunsaturated fatty acids (PUFAs). A scan of Inuit genomes for signatures of adaptation revealed signals at several loci, with the strongest signal located in a cluster of fatty acid desaturases that determine PUFA levels. The selected alleles are associated with multiple metabolic and anthropometric phenotypes and have large effect sizes for weight and height, with the effect on height replicated in Europeans. By analyzing membrane lipids, we found that the selected alleles modulate fatty acid composition, which may affect the regulation of growth hormones. Thus, the Inuit have genetic and physiological adaptations to a diet rich in PUFAs.
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            Genetic associations at 53 loci highlight cell types and biological pathways relevant for kidney function

            Reduced glomerular filtration rate defines chronic kidney disease and is associated with cardiovascular and all-cause mortality. We conducted a meta-analysis of genome-wide association studies for estimated glomerular filtration rate (eGFR), combining data across 133,413 individuals with replication in up to 42,166 individuals. We identify 24 new and confirm 29 previously identified loci. Of these 53 loci, 19 associate with eGFR among individuals with diabetes. Using bioinformatics, we show that identified genes at eGFR loci are enriched for expression in kidney tissues and in pathways relevant for kidney development and transmembrane transporter activity, kidney structure, and regulation of glucose metabolism. Chromatin state mapping and DNase I hypersensitivity analyses across adult tissues demonstrate preferential mapping of associated variants to regulatory regions in kidney but not extra-renal tissues. These findings suggest that genetic determinants of eGFR are mediated largely through direct effects within the kidney and highlight important cell types and biological pathways.
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              Prevalence and Disease Burden of Chronic Kidney Disease.

              Chronic kidney disease (CKD) has been recognized as a leading public health problem worldwide. The global estimated prevalence of CKD is 13.4% (11.7-15.1%), and patients with end-stage kidney disease (ESKD) needing renal replacement therapy is estimated between 4.902 and 7.083 million. Through its effect on cardiovascular risk and ESKD, CKD directly affects the global burden of morbidity and mortality worldwide. The global increase in this disease is mainly driven by the increase in the prevalence of diabetes mellitus, hypertension, obesity, and aging. But in some regions, other causes such as infection, herbal and environmental toxins are still common. The large number of deaths for poor access to renal replacement therapy in developing countries, and also large increase of patients with ESKD in future, will produce substantial financial burden for even the most wealthy countries. Cost-effectiveness of preventive strategies to reduce the disease burden should be evaluated in relation to the local economic development and resource. Strategies reducing the cardiovascular risk in CKD still need further evaluation in large trials especially including patients with advanced kidney disease or end-stage kidney disease.
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                Author and article information

                Contributors
                Journal
                Front Genet
                Front Genet
                Front. Genet.
                Frontiers in Genetics
                Frontiers Media S.A.
                1664-8021
                16 September 2021
                2021
                : 12
                : 716151
                Affiliations
                [1] 1Urology and Nephrology Research Center, Shahid Beheshti University of Medical Sciences , Tehran, Iran
                [2] 2Men’s Health and Reproductive Health Research Center, Shahid Beheshti University of Medical Sciences , Tehran, Iran
                [3] 3Phytochemistry Research Center, Shahid Beheshti University of Medical Sciences , Tehran, Iran
                [4] 4Department of Laboratory Sciences, School of Paramedical Sciences, Torbat Heydariyeh University of Medical Sciences , Torbat Heydariyeh, Iran
                [5] 5Neuroscience Research Center, Torbat Heydariyeh University of Medical Sciences , Torbat Heydariyeh, Iran
                [6] 6Skull Base Research Center, Loghman Hakim Hospital, Shahid Beheshti University of Medical Sciences , Tehran, Iran
                [7] 7Department of Medical Genetics, School of Medicine, Shahid Beheshti University of Medical Sciences , Tehran, Iran
                Author notes

                Edited by: José M. Álvarez-Castro, University of Santiago de Compostela, Spain

                Reviewed by: Filippo Biscarini, National Research Council (CNR), Italy; Jin Ok Yang, Korean Bioinformation Center, Korea Research Institute of Bioscience and Biotechnology, South Korea

                *Correspondence: Mohammad Taheri, Mohammad_823@ 123456yahoo.com
                Soudeh Ghafouri-Fard, s.ghafourifard@ 123456sbmu.ac.ir

                This article was submitted to Applied Genetic Epidemiology, a section of the journal Frontiers in Genetics

                Article
                10.3389/fgene.2021.716151
                8481823
                5b43208d-a464-4c68-9d89-7400b6bcecfa
                Copyright © 2021 Miladipour, Gholipour, Honarmand Tamizkar, Abak, Kholghi Oskooei, Taheri and Ghafouri-Fard.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 01 June 2021
                : 12 August 2021
                Page count
                Figures: 0, Tables: 4, Equations: 0, References: 24, Pages: 6, Words: 4618
                Categories
                Genetics
                Original Research

                Genetics
                fads1,fads2,fads3,polymorphisms,hemodialysis
                Genetics
                fads1, fads2, fads3, polymorphisms, hemodialysis

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