Microsatellite typing for DRB1 alleles: application to the analysis of HLA associations with rheumatoid arthritis.
The current methods for molecular typing of HLA-DR alleles incur a substantial financial burden when performing large population studies. In the current study, we aimed to provide much less expensive typing approach with high predictability for DRB1 genotype. We have used a panel of three microsatellite markers in the class II region (D6S2666, D6S2665 and D6S2446) for genotyping and haplotype reconstruction in a total of 1687 Caucasian (1313 RA patients and 374 controls) and 1364 Korean individuals (744 RA patients and 620 controls), all of whom were previously genotyped for DRB1. We found that a total of 88.4 and 87.4% of all observed three-marker haplotypes could determine the DR type with a positive predictive value >0.8 with high sensitivity and specificity. There was a high degree of haplotype conservation when comparing Caucasian and Asian populations. Interestingly, we found that the majority of DRB1*09 and DRB1*10 alleles share a common three-marker haplotype in both Caucasian and Asian populations. This is unexpected, since these two alleles are found on very different haplotype families. In addition, these two alleles are both associated with rheumatoid arthritis, making the elucidation of these haplotype relationships potentially important for understanding disease susceptibility.
Lee
H-S
HS
Feinstein Institute for Medical Research, North Shore LIJ Health System, Manhasset, NY 11030, USA.
Li
W
W
Lee
A
A
Rodine
P
P
Graham
R R
RR
Ortmann
W A
WA
Batliwalla
F
F
Lee
K W
KW
Bae
S C
SC
Behrens
T W
TW
Gregersen
P K
PK
D000483:Alleles; D001172:Arthritis, Rheumatoid / Q000235:genetics* / Q000276:immunology*; D044466:Asian People / Q000235:genetics; D016022:Case-Control Studies; D005787:Gene Frequency; D006684:HLA-DR Antigens / Q000235:genetics*; D059811:HLA-DRB1 Chains; D006239:Haplotypes; D006650:Histocompatibility Testing / Q000379:methods* / Q000706:statistics & numerical data; D006801:Humans; D007723:Korea; D018895:Microsatellite Repeats; D009656:North America; D012680:Sensitivity and Specificity; D044465:White People / Q000235:genetics
D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains