BACKGROUND/AIMS: The NOS3 gene is a biological and positional candidate for diabetic nephropathy. However, the relationship between NOS3 polymorphisms and renal disease is inconclusive. This study aimed to clarify the association of NOS3 variants with nephropathy in individuals with type 1 diabetes. METHODS: We conducted a case-control study examining all common SNPs in the NOS3 gene by a tag SNP approach. Individuals with type 1 diabetes and persistent proteinuria (cases, n = 718) were compared with individuals with type 1 diabetes but no evidence of renal disease (controls, n = 749). Our replication collection comprised 1,105 individuals with type 1 diabetes recruited to a nephropathy case group and 862 control individuals with normal urinary albumin excretion rates. Meta-analysis was conducted for SNPs where more than three genotype datasets were available. RESULTS: A novel association was identified in the discovery collection (rs1800783, p(genotype) = 0.006, p(allele) = 0.002, OR = 1.26, 95% CI: 1.08-1.47) and supported by independent replication using a tag SNP (rs4496877, pairwise r² = 0.96 with rs1800783) in the replication collection (p(genotype) = 0.002, p(allele) = 0.0006, OR = 1.27, 95% CI: 1.10-1.45). CONCLUSION: The A allele of rs1800783 is a significant risk factor for nephropathy in individuals with type 1 diabetes, and further comprehensive studies are warranted to confirm the definitive functional variant in the NOS3 gene.
BACKGROUND/AIMS: The NOS3 gene is a biological and positional candidate for diabetic nephropathy. However, the relationship between NOS3 polymorphisms and renal disease is inconclusive. This study aimed to clarify the association of NOS3 variants with nephropathy in individuals with type 1 diabetes. METHODS: We conducted a case-control study examining all common SNPs in the NOS3 gene by a tag SNP approach. Individuals with type 1 diabetes and persistent proteinuria (cases, n = 718) were compared with individuals with type 1 diabetes but no evidence of renal disease (controls, n = 749). Our replication collection comprised 1,105 individuals with type 1 diabetes recruited to a nephropathy case group and 862 control individuals with normal urinary albumin excretion rates. Meta-analysis was conducted for SNPs where more than three genotype datasets were available. RESULTS: A novel association was identified in the discovery collection (rs1800783, p(genotype) = 0.006, p(allele) = 0.002, OR = 1.26, 95% CI: 1.08-1.47) and supported by independent replication using a tag SNP (rs4496877, pairwise r² = 0.96 with rs1800783) in the replication collection (p(genotype) = 0.002, p(allele) = 0.0006, OR = 1.27, 95% CI: 1.10-1.45). CONCLUSION: The A allele of rs1800783 is a significant risk factor for nephropathy in individuals with type 1 diabetes, and further comprehensive studies are warranted to confirm the definitive functional variant in the NOS3 gene.
Authors: Eugene J Barrett; Zhenqi Liu; Mogher Khamaisi; George L King; Ronald Klein; Barbara E K Klein; Timothy M Hughes; Suzanne Craft; Barry I Freedman; Donald W Bowden; Aaron I Vinik; Carolina M Casellini Journal: J Clin Endocrinol Metab Date: 2017-12-01 Impact factor: 5.958
Authors: Rany M Salem; Jennifer N Todd; Niina Sandholm; Joanne B Cole; Wei-Min Chen; Darrell Andrews; Marcus G Pezzolesi; Paul M McKeigue; Linda T Hiraki; Chengxiang Qiu; Viji Nair; Chen Di Liao; Jing Jing Cao; Erkka Valo; Suna Onengut-Gumuscu; Adam M Smiles; Stuart J McGurnaghan; Jani K Haukka; Valma Harjutsalo; Eoin P Brennan; Natalie van Zuydam; Emma Ahlqvist; Ross Doyle; Tarunveer S Ahluwalia; Maria Lajer; Maria F Hughes; Jihwan Park; Jan Skupien; Athina Spiliopoulou; Andrew Liu; Rajasree Menon; Carine M Boustany-Kari; Hyun M Kang; Robert G Nelson; Ronald Klein; Barbara E Klein; Kristine E Lee; Xiaoyu Gao; Michael Mauer; Silvia Maestroni; Maria Luiza Caramori; Ian H de Boer; Rachel G Miller; Jingchuan Guo; Andrew P Boright; David Tregouet; Beata Gyorgy; Janet K Snell-Bergeon; David M Maahs; Shelley B Bull; Angelo J Canty; Colin N A Palmer; Lars Stechemesser; Bernhard Paulweber; Raimund Weitgasser; Jelizaveta Sokolovska; Vita Rovīte; Valdis Pīrāgs; Edita Prakapiene; Lina Radzeviciene; Rasa Verkauskiene; Nicolae Mircea Panduru; Leif C Groop; Mark I McCarthy; Harvest F Gu; Anna Möllsten; Henrik Falhammar; Kerstin Brismar; Finian Martin; Peter Rossing; Tina Costacou; Gianpaolo Zerbini; Michel Marre; Samy Hadjadj; Amy J McKnight; Carol Forsblom; Gareth McKay; Catherine Godson; A Peter Maxwell; Matthias Kretzler; Katalin Susztak; Helen M Colhoun; Andrzej Krolewski; Andrew D Paterson; Per-Henrik Groop; Stephen S Rich; Joel N Hirschhorn; Jose C Florez Journal: J Am Soc Nephrol Date: 2019-09-19 Impact factor: 14.978
Authors: Sarah ElHajj Chehadeh; Noura S Sayed; Hanin S Abdelsamad; Wael Almahmeed; Ahsan H Khandoker; Herbert F Jelinek; Habiba S Alsafar Journal: Front Endocrinol (Lausanne) Date: 2022-01-06 Impact factor: 5.555