AIMS/HYPOTHESIS: In the past few years, several genes outside the MHC region have been described as new susceptibility genetic factors to type 1 diabetes. An association between CAPSL-rs1445898 and type 1 diabetes was reported in a large white population and corroborated in a genome-wide analysis, which also found an association with IL7R, which is located adjacent to CAPSL. The aim of this study was to replicate the aforementioned associations in independent cohorts. METHODS: We analysed two CAPSL (rs1010601 and rs1445898) and three IL7R (rs6897932, rs987106 and rs3194051) polymorphisms. All these single nucleotide polymorphisms (SNPs) were genotyped using TaqMan minor groove binder chemistry in 301 unrelated Spanish type 1 diabetes patients and 646 healthy controls. Additionally, the associated CAPSL SNP rs1445898 was genotyped in a Dutch cohort consisting of 429 type 1 diabetes patients and 720 healthy controls. RESULTS: The homozygous mutant genotype of the CAPSL SNP rs1445898 showed a trend towards a protective effect in the overall Spanish cohort (OR [95% CI] 0.70 [0.44-1.09]; p = 0.09) and in the Dutch cohort (OR [95% CI] 0.74 [0.51-1.05]; p = 0.09). Pooling of both cohorts was performed, yielding a statistically significant difference (Mantel-Haenszel OR 0.71; p = 0.005). This protective effect was significantly different in early-onset vs late-onset Spanish patients (OR [95% CI] 0.26 [0.10-0.65]; p = 0.001). Similarly, in the early-onset subgroup, the homozygous mutant genotype of the IL7R SNP rs6897932 showed a similar protective effect (OR [95% CI] 0.18 [0.02-0.94]; p = 0.02). CONCLUSIONS/ INTERPRETATION: In summary, we describe an independent replication of the association between the CAPSL-IL7R locus and type 1 diabetes, especially for early-onset type 1 diabetes patients.
AIMS/HYPOTHESIS: In the past few years, several genes outside the MHC region have been described as new susceptibility genetic factors to type 1 diabetes. An association between CAPSL-rs1445898 and type 1 diabetes was reported in a large white population and corroborated in a genome-wide analysis, which also found an association with IL7R, which is located adjacent to CAPSL. The aim of this study was to replicate the aforementioned associations in independent cohorts. METHODS: We analysed two CAPSL (rs1010601 and rs1445898) and three IL7R (rs6897932, rs987106 and rs3194051) polymorphisms. All these single nucleotide polymorphisms (SNPs) were genotyped using TaqMan minor groove binder chemistry in 301 unrelated Spanish type 1 diabetespatients and 646 healthy controls. Additionally, the associated CAPSL SNP rs1445898 was genotyped in a Dutch cohort consisting of 429 type 1 diabetespatients and 720 healthy controls. RESULTS: The homozygous mutant genotype of the CAPSL SNP rs1445898 showed a trend towards a protective effect in the overall Spanish cohort (OR [95% CI] 0.70 [0.44-1.09]; p = 0.09) and in the Dutch cohort (OR [95% CI] 0.74 [0.51-1.05]; p = 0.09). Pooling of both cohorts was performed, yielding a statistically significant difference (Mantel-Haenszel OR 0.71; p = 0.005). This protective effect was significantly different in early-onset vs late-onset Spanish patients (OR [95% CI] 0.26 [0.10-0.65]; p = 0.001). Similarly, in the early-onset subgroup, the homozygous mutant genotype of the IL7R SNP rs6897932 showed a similar protective effect (OR [95% CI] 0.18 [0.02-0.94]; p = 0.02). CONCLUSIONS/ INTERPRETATION: In summary, we describe an independent replication of the association between the CAPSL-IL7R locus and type 1 diabetes, especially for early-onset type 1 diabetespatients.
Authors: Stacey B Gabriel; Stephen F Schaffner; Huy Nguyen; Jamie M Moore; Jessica Roy; Brendan Blumenstiel; John Higgins; Matthew DeFelice; Amy Lochner; Maura Faggart; Shau Neen Liu-Cordero; Charles Rotimi; Adebowale Adeyemo; Richard Cooper; Ryk Ward; Eric S Lander; Mark J Daly; David Altshuler Journal: Science Date: 2002-05-23 Impact factor: 47.728
Authors: Hironori Ueda; Joanna M M Howson; Laura Esposito; Joanne Heward; Hywel Snook; Giselle Chamberlain; Daniel B Rainbow; Kara M D Hunter; Annabel N Smith; Gianfranco Di Genova; Mathias H Herr; Ingrid Dahlman; Felicity Payne; Deborah Smyth; Christopher Lowe; Rebecca C J Twells; Sarah Howlett; Barry Healy; Sarah Nutland; Helen E Rance; Vin Everett; Luc J Smink; Alex C Lam; Heather J Cordell; Neil M Walker; Cristina Bordin; John Hulme; Costantino Motzo; Francesco Cucca; J Fred Hess; Michael L Metzker; Jane Rogers; Simon Gregory; Amit Allahabadia; Ratnasingam Nithiyananthan; Eva Tuomilehto-Wolf; Jaakko Tuomilehto; Polly Bingley; Kathleen M Gillespie; Dag E Undlien; Kjersti S Rønningen; Cristian Guja; Constantin Ionescu-Tîrgovişte; David A Savage; A Peter Maxwell; Dennis J Carson; Chris C Patterson; Jayne A Franklyn; David G Clayton; Laurence B Peterson; Linda S Wicker; John A Todd; Stephen C L Gough Journal: Nature Date: 2003-04-30 Impact factor: 49.962
Authors: Patrick Concannon; Henry A Erlich; Cecile Julier; Grant Morahan; Jørn Nerup; Flemming Pociot; John A Todd; Stephen S Rich Journal: Diabetes Date: 2005-10 Impact factor: 9.461
Authors: Deborah J Smyth; Jason D Cooper; Rebecca Bailey; Sarah Field; Oliver Burren; Luc J Smink; Cristian Guja; Constantin Ionescu-Tirgoviste; Barry Widmer; David B Dunger; David A Savage; Neil M Walker; David G Clayton; John A Todd Journal: Nat Genet Date: 2006-05-14 Impact factor: 38.330
Authors: L Nisticò; R Buzzetti; L E Pritchard; B Van der Auwera; C Giovannini; E Bosi; M T Larrad; M S Rios; C C Chow; C S Cockram; K Jacobs; C Mijovic; S C Bain; A H Barnett; C L Vandewalle; F Schuit; F K Gorus; R Tosi; P Pozzilli; J A Todd Journal: Hum Mol Genet Date: 1996-07 Impact factor: 6.150
Authors: Laura Espino-Paisan; Hermenegildo de la Calle; Miguel Fernández-Arquero; Maria Angeles Figueredo; Emilio G de la Concha; Elena Urcelay; Jose Luis Santiago Journal: Immunogenetics Date: 2011-01-19 Impact factor: 2.846
Authors: Shoshana D Katzman; Katrina K Hoyer; Hans Dooms; Iris K Gratz; Michael D Rosenblum; Jonathan S Paw; Sara H Isakson; Abul K Abbas Journal: Cytokine Date: 2011-07-31 Impact factor: 3.861
Authors: Iana H Haralambieva; Inna G Ovsyannikova; Richard B Kennedy; Robert A Vierkant; V Shane Pankratz; Robert M Jacobson; Gregory A Poland Journal: Vaccine Date: 2011-08-27 Impact factor: 3.641