AIMS/HYPOTHESIS: The HLA class II DQB1*0602 allele confers strong dominant protection against type 1 diabetes but protection is not absolute. The aim of this study was to identify markers within the HLA region that differentiate DQB1*0602 haplotypes and show different associations with disease risk. METHODS: We defined alleles at eight microsatellite markers spanning the HLA region in a case-control cohort from Sweden. RESULTS: We found that allele 15 at marker D6S265 (109 kb centromeric of HLA-A) was over-represented among patients carrying DRB1*15, DQB1*0602. A detailed haplotype analysis showed that DRB1*15, DQB1*0602 haplotypes carrying D6S265*15 have a ten-fold higher odds ratio (OR) than those carrying other alleles and thus confer reduced protection [OR D6S265*15=0.186 (95% CI 0.074, 0.472) vs OR D6S265*15-=0.017 (95% CI 0.005, 0.062), p<0.001]. CONCLUSIONS/ INTERPRETATION: Our data support the existence of a locus that modifies the protective effect associated with DQB1*0602. Typing for allele D6S265*15 can identify a less protective DQB1*0602 haplotype, thereby allowing a more accurate prediction of type 1 diabetes risk.
AIMS/HYPOTHESIS: The HLA class II DQB1*0602 allele confers strong dominant protection against type 1 diabetes but protection is not absolute. The aim of this study was to identify markers within the HLA region that differentiate DQB1*0602 haplotypes and show different associations with disease risk. METHODS: We defined alleles at eight microsatellite markers spanning the HLA region in a case-control cohort from Sweden. RESULTS: We found that allele 15 at marker D6S265 (109 kb centromeric of HLA-A) was over-represented among patients carrying DRB1*15, DQB1*0602. A detailed haplotype analysis showed that DRB1*15, DQB1*0602 haplotypes carrying D6S265*15 have a ten-fold higher odds ratio (OR) than those carrying other alleles and thus confer reduced protection [OR D6S265*15=0.186 (95% CI 0.074, 0.472) vs OR D6S265*15-=0.017 (95% CI 0.005, 0.062), p<0.001]. CONCLUSIONS/ INTERPRETATION: Our data support the existence of a locus that modifies the protective effect associated with DQB1*0602. Typing for allele D6S265*15 can identify a less protective DQB1*0602 haplotype, thereby allowing a more accurate prediction of type 1 diabetes risk.
Authors: J Graham; I Kockum; C B Sanjeevi; M Landin-Olsson; L Nyström; G Sundkvist; H Arnqvist; G Blohmé; F Lithner; B Littorin; B Scherstén; L Wibell; J Ostman; A Lernmark; N Breslow; G Dahlquist Journal: Eur J Immunogenet Date: 1999 Apr-Jun
Authors: A Pugliese; E Kawasaki; M Zeller; L Yu; S Babu; M Solimena; C T Moraes; M Pietropaolo; R P Friday; M Trucco; C Ricordi; M Allen; J A Noble; H A Erlich; G S Eisenbarth Journal: J Clin Endocrinol Metab Date: 1999-05 Impact factor: 5.958
Authors: Jinko Graham; William A Hagopian; Ingrid Kockum; Lou Sheng Li; Carani B Sanjeevi; Robert M Lowe; Jonathan B Schaefer; Marjan Zarghami; Heather L Day; Mona Landin-Olsson; Jerry P Palmer; Marta Janer-Villanueva; Leroy Hood; Göran Sundkvist; Ake Lernmark; Norman Breslow; Gisela Dahlquist; Göran Blohmé Journal: Diabetes Date: 2002-05 Impact factor: 9.461
Authors: Janelle A Noble; Ana M Valdes; Teodorica L Bugawan; Raymond J Apple; Glenys Thomson; Henry A Erlich Journal: Hum Immunol Date: 2002-08 Impact factor: 2.850
Authors: M Landin-Olsson; J P Palmer; A Lernmark; L Blom; G Sundkvist; L Nyström; G Dahlquist Journal: Diabetologia Date: 1992-11 Impact factor: 10.122
Authors: A Pugliese; R Gianani; R Moromisato; Z L Awdeh; C A Alper; H A Erlich; R A Jackson; G S Eisenbarth Journal: Diabetes Date: 1995-06 Impact factor: 9.461
Authors: H F Harbo; B A Lie; S Sawcer; E G Celius; K-Z Dai; A Oturai; J Hillert; A R Lorentzen; M Laaksonen; K-M Myhr; L P Ryder; S Fredrikson; H Nyland; P S Sørensen; M Sandberg-Wollheim; O Andersen; A Svejgaard; A Edland; S I Mellgren; A Compston; F Vartdal; A Spurkland Journal: Tissue Antigens Date: 2004-03
Authors: Alberto Pugliese; David Boulware; Liping Yu; Sunanda Babu; Andrea K Steck; Dorothy Becker; Henry Rodriguez; Linda DiMeglio; Carmella Evans-Molina; Leonard C Harrison; Desmond Schatz; Jerry P Palmer; Carla Greenbaum; George S Eisenbarth; Jay M Sosenko Journal: Diabetes Date: 2016-01-28 Impact factor: 9.461
Authors: Henry Erlich; Ana Maria Valdes; Janelle Noble; Joyce A Carlson; Mike Varney; Pat Concannon; Josyf C Mychaleckyj; John A Todd; Persia Bonella; Anna Lisa Fear; Eva Lavant; Anthony Louey; Priscilla Moonsamy Journal: Diabetes Date: 2008-02-05 Impact factor: 9.461
Authors: Jared R Lowe; Daniel J Perry; April K S Salama; Clayton E Mathews; Larry G Moss; Brent A Hanks Journal: J Immunother Cancer Date: 2016-12-20 Impact factor: 13.751
Authors: Nicholas J Thomas; John M Dennis; Seth A Sharp; Akaal Kaur; Shivani Misra; Helen C Walkey; Desmond G Johnston; Nick S Oliver; William A Hagopian; Michael N Weedon; Kashyap A Patel; Richard A Oram Journal: Diabetologia Date: 2021-07-16 Impact factor: 10.122