D6S265*15 marks a DRB1*15, DQB1*0602 haplotype associated with attenuated protection from type 1 diabetes mellitus.
OBJECTIVE
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
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.
Valdes
A M
AM
Department of Integrative Biology, University of California, Berkeley, CA, USA.
Thomson
G
G
Graham
J
J
Zarghami
M
M
McNeney
B
B
Kockum
I
I
Smith
A
A
Lathrop
M
M
Steenkiste
A R
AR
Dorman
J S
JS
Noble
J A
JA
Hansen
J A
JA
Pugliese
A
A
Lernmark
A
A
D000328:Adult; D000483:Alleles; D016022:Case-Control Studies; D002874:Chromosome Mapping; D015331:Cohort Studies; D003922:Diabetes Mellitus, Type 1 / Q000453:epidemiology / Q000235:genetics* / Q000517:prevention & control; D005260:Female; D020022:Genetic Predisposition to Disease; D006683:HLA-DQ Antigens / Q000235:genetics*; D059866:HLA-DQ beta-Chains; D006684:HLA-DR Antigens / Q000235:genetics*; D059811:HLA-DRB1 Chains; D006239:Haplotypes / Q000235:genetics*; D006801:Humans; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics*; D018895:Microsatellite Repeats; D008875:Middle Aged; D016017:Odds Ratio; D011237:Predictive Value of Tests; D012306:Risk; D013548:Sweden / Q000453:epidemiology
D006683:HLA-DQ Antigens; D059866:HLA-DQ beta-Chains; C069051:HLA-DQB1 antigen; D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains; D008562:Membrane Glycoproteins