Different HLA-DRB1 allele distributions in distinct clinical subgroups of sarcoidosis patients.
BACKGROUND
A strong genetic influence by the MHC class II region has been reported in sarcoidosis, however in many studies with different results. This may possibly be caused by actual differences between distinct ethnic groups, too small sample sizes, or because of lack of accurate clinical subgrouping.


METHODS
In this study we HLA typed a large patient population (n = 754) recruited from one single centre. Patients were sub-grouped into those with Löfgren's syndrome (LS) (n = 302) and those without (non-Löfgren's) (n = 452), and the majority of them were clinically classified into those with recovery within two years (resolving) and those with signs of disease for more than two years (non-resolving). PCR was used for determination of HLA-DRB1 alleles. Swedish healthy blood donors (n = 1366) served as controls.


RESULTS
There was a dramatic difference in the distribution of HLA alleles in LS compared to non-LS patients (p = 4 x 10(-36)). Most notably, DRB1*01, DRB1*03 and DRB1*14, clearly differed in LS and non-LS patients. In relation to disease course, DRB1*07, DRB1*14 and DRB1*15 generally associated with, while DRB1*01 and DRB1*03 protected against, a non-resolving disease. Interestingly, the clinical influence of DRB1*03 (good prognosis) dominated over that of DRB1*15 (bad prognosis).


CONCLUSIONS
We found several significant differences between LS and non-LS patients and we therefore suggest that genetic association studies in sarcoidosis should include a careful clinical characterisation and sub-grouping of patients, in order to reveal true genetic associations. This may be particularly accurate to do in the heterogeneous non-LS group of patients.
Grunewald
Johan
J
Department of Medicine, Division of Respiratory Medicine, Karolinska University Hospital Solna, Sweden. johan.grunewald@ki.se
Brynedal
Boel
B
Darlington
Pernilla
P
Nisell
Magnus
M
Cederlund
Kerstin
K
Hillert
Jan
J
Eklund
Anders
A
D000328:Adult; D000368:Aged; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease / Q000453:epidemiology* / Q000235:genetics*; D006684:HLA-DR Antigens / Q000235:genetics*; D059811:HLA-DRB1 Chains; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D015995:Prevalence; D018570:Risk Assessment / Q000379:methods; D012307:Risk Factors; D017565:Sarcoidosis, Pulmonary / Q000453:epidemiology* / Q000235:genetics*; D013548:Sweden / Q000453:epidemiology; D055815:Young Adult
D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains