Decreased Insulin Secretion and Increased Risk of Type 2 Diabetes Associated with Allelic Variations of the WFS1 Gene: the Data from Epidemiological Study on the Insulin Resistance Syndrome (DESIR) Prospective Study

Overview

Journal Diabetologia

Specialty Endocrinology

Date 2010 Dec 4

PMID 21127832

Citations 19

Authors

N Cheurfa

G M Brenner

A F Reis

D Dubois-Laforgue

R Roussel

J Tichet

O Lantieri

B Balkau

F Fumeron

J Timsit

M Marre

G Velho

Affiliations

Soon will be listed here.

Abstract

Aims/hypothesis: We investigated associations of allelic variations in the WFS1 gene with insulin secretion and risk of type 2 diabetes in a general population prospective study.

Methods: We studied 5,110 unrelated French men and women who participated in the prospective Data from Epidemiological Study on the Insulin Resistance Syndrome (DESIR) study. Additional cross-sectional analyses were performed on 4,472 French individuals with type 2 diabetes and 3,065 controls. Three single nucleotide polymorphisms (SNPs) were genotyped: rs10010131, rs1801213/rs7672995 and rs734312.

Results: We observed statistically significant associations between the major alleles of the three variants and prevalent type 2 diabetes in the DESIR cohort at baseline. Cox analyses showed an association between the G-allele of rs10010131 and incident type 2 diabetes (HR 1.34, 95% CI 1.08-1.70, p = 0.007). Similar results were observed for the G-allele of rs1801213 and the A-allele of rs734312. The GGA haplotype was associated with an increased risk of diabetes as compared with the ACG haplotype (HR 1.26, 95% CI 1.04-1.42, p = 0.02). We also observed statistically significant associations of the three SNPs with plasma glucose, HbA(1c) levels and insulin secretion at baseline and throughout the study in individuals with type 2 diabetes or at risk of developing diabetes. However, no association was observed in those who remained normoglycaemic at the end of the follow-up. Associations between the three variants and type 2 diabetes were replicated in cross-sectional studies of type 2 diabetic patients in comparison with a non-diabetic control group.

Conclusions/interpretation: The most frequent haplotype at the haplotype block containing the WFS1 gene modulated insulin secretion and was associated with an increased risk of type 2 diabetes.

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References

Fonseca S, Lipson K, Urano F . Endoplasmic reticulum stress signaling in pancreatic beta-cells. Antioxid Redox Signal. 2007; 9(12):2335-44. DOI: 10.1089/ars.2007.1790. View

Riggs A, Bernal-Mizrachi E, Ohsugi M, Wasson J, Fatrai S, Welling C . Mice conditionally lacking the Wolfram gene in pancreatic islet beta cells exhibit diabetes as a result of enhanced endoplasmic reticulum stress and apoptosis. Diabetologia. 2005; 48(11):2313-21. DOI: 10.1007/s00125-005-1947-4. View

Marre M, Lievre M, Chatellier G, Mann J, Passa P, Menard J . Effects of low dose ramipril on cardiovascular and renal outcomes in patients with type 2 diabetes and raised excretion of urinary albumin: randomised, double blind, placebo controlled trial (the DIABHYCAR study). BMJ. 2004; 328(7438):495. PMC: 351842. DOI: 10.1136/bmj.37970.629537.0D. View

Tregouet D, Escolano S, Tiret L, Mallet A, Golmard J . A new algorithm for haplotype-based association analysis: the Stochastic-EM algorithm. Ann Hum Genet. 2004; 68(Pt 2):165-77. DOI: 10.1046/j.1529-8817.2003.00085.x. View

Cnop M, Ladriere L, Hekerman P, Ortis F, Cardozo A, Dogusan Z . Selective inhibition of eukaryotic translation initiation factor 2 alpha dephosphorylation potentiates fatty acid-induced endoplasmic reticulum stress and causes pancreatic beta-cell dysfunction and apoptosis. J Biol Chem. 2006; 282(6):3989-97. DOI: 10.1074/jbc.M607627200. View

Eizirik D, Cardozo A, Cnop M . The role for endoplasmic reticulum stress in diabetes mellitus. Endocr Rev. 2007; 29(1):42-61. DOI: 10.1210/er.2007-0015. View

Dina C, Meyre D, Gallina S, Durand E, Korner A, Jacobson P . Variation in FTO contributes to childhood obesity and severe adult obesity. Nat Genet. 2007; 39(6):724-6. DOI: 10.1038/ng2048. View

Holst J, Vilsboll T, Deacon C . The incretin system and its role in type 2 diabetes mellitus. Mol Cell Endocrinol. 2008; 297(1-2):127-36. DOI: 10.1016/j.mce.2008.08.012. View

Wallace T, Levy J, Matthews D . Use and abuse of HOMA modeling. Diabetes Care. 2004; 27(6):1487-95. DOI: 10.2337/diacare.27.6.1487. View

10.

Lipson K, Fonseca S, Ishigaki S, Nguyen L, Foss E, Bortell R . Regulation of insulin biosynthesis in pancreatic beta cells by an endoplasmic reticulum-resident protein kinase IRE1. Cell Metab. 2006; 4(3):245-54. DOI: 10.1016/j.cmet.2006.07.007. View

11.

Balkau B, Lange C, Fezeu L, Tichet J, de Lauzon-Guillain B, Czernichow S . Predicting diabetes: clinical, biological, and genetic approaches: data from the Epidemiological Study on the Insulin Resistance Syndrome (DESIR). Diabetes Care. 2008; 31(10):2056-61. PMC: 2551654. DOI: 10.2337/dc08-0368. View

12.

Sandhu M, Weedon M, Fawcett K, Wasson J, Debenham S, Daly A . Common variants in WFS1 confer risk of type 2 diabetes. Nat Genet. 2007; 39(8):951-3. PMC: 2672152. DOI: 10.1038/ng2067. View

13.

Fonseca S, Ishigaki S, Oslowski C, Lu S, Lipson K, Ghosh R . Wolfram syndrome 1 gene negatively regulates ER stress signaling in rodent and human cells. J Clin Invest. 2010; 120(3):744-55. PMC: 2827948. DOI: 10.1172/JCI39678. View

14.

Fonseca S, Fukuma M, Lipson K, Nguyen L, Allen J, Oka Y . WFS1 is a novel component of the unfolded protein response and maintains homeostasis of the endoplasmic reticulum in pancreatic beta-cells. J Biol Chem. 2005; 280(47):39609-15. DOI: 10.1074/jbc.M507426200. View

15.

Schafer S, Mussig K, Staiger H, Machicao F, Stefan N, Gallwitz B . A common genetic variant in WFS1 determines impaired glucagon-like peptide-1-induced insulin secretion. Diabetologia. 2009; 52(6):1075-82. DOI: 10.1007/s00125-009-1344-5. View

16.

Simonis-Bik A, Nijpels G, van Haeften T, Houwing-Duistermaat J, Boomsma D, Reiling E . Gene variants in the novel type 2 diabetes loci CDC123/CAMK1D, THADA, ADAMTS9, BCL11A, and MTNR1B affect different aspects of pancreatic beta-cell function. Diabetes. 2009; 59(1):293-301. PMC: 2797936. DOI: 10.2337/db09-1048. View

17.

Stancakova A, Kuulasmaa T, Paananen J, Jackson A, Bonnycastle L, Collins F . Association of 18 confirmed susceptibility loci for type 2 diabetes with indices of insulin release, proinsulin conversion, and insulin sensitivity in 5,327 nondiabetic Finnish men. Diabetes. 2009; 58(9):2129-36. PMC: 2731523. DOI: 10.2337/db09-0117. View

18.

Fawcett K, Wheeler E, Morris A, Ricketts S, Hallmans G, Rolandsson O . Detailed investigation of the role of common and low-frequency WFS1 variants in type 2 diabetes risk. Diabetes. 2009; 59(3):741-6. PMC: 2828659. DOI: 10.2337/db09-0920. View

19.

Yusta B, Baggio L, Estall J, Koehler J, Holland D, Li H . GLP-1 receptor activation improves beta cell function and survival following induction of endoplasmic reticulum stress. Cell Metab. 2006; 4(5):391-406. DOI: 10.1016/j.cmet.2006.10.001. View

20.

Lievre M, Marre M, Chatellier G, Plouin P, Reglier J, Richardson L . The non-insulin-dependent diabetes, hypertension, microalbuminuria or proteinuria, cardiovascular events, and ramipril (DIABHYCAR) study: design, organization, and patient recruitment. DIABHYCAR Study Group. Control Clin Trials. 2000; 21(4):383-96. DOI: 10.1016/s0197-2456(00)00060-x. View