Clinical features of sarcoidosis in relation to HLA distribution and HLA-DRB3 genotyping by PCR-RFLP.
BACKGROUND
Susceptibility to the development of sarcoidosis has been demonstrated to be associated with HLA-DR5, -DR6, and -DR8 encoded by the DRB1 gene. However, involvement of the DRB3 (HLA-DR52) gene in the development of sarcoidosis remains unclear.


METHODS
HLA-DRB3 genotyping was performed using the PCR-RFLP method and the clinical features of the patients with and without the DR3, 5, 6, 8 group antigens were compared.


RESULTS
HLA-DRB3 genotyping indicated an association between DRB3*0101 and sarcoidosis. The DR8 haplotype lacking the DRB3 gene has been found to be increased significantly in sarcoidosis, suggesting that the HLA-DRB3 gene is not a primary determinant of predisposition to sarcoidosis. The association of DRB3*0101 with sarcoidosis is attributable to linkage disequilibrium with DR5- and DR6-associated alleles. There were significant decreases in the DR3, 5, 6, 8 group (DR5, DR6, or DR8) antigen frequencies in patients with retinal perivasculitis, high intraocular pressure (or secondary glaucoma), and optic nerve and/or macular lesion. Correlations were observed among the DR3, 5, 6, 8 group antigens, early onset sarcoidosis and disease with fewer intraocular lesions.


CONCLUSIONS
This established a molecular basis for some of the clinical heterogeneity observed in sarcoidosis.
Ishihara
M
M
Department of Ophthalmology, Yokohama City University School of Medicine, Kanagawa, Japan.
Ishida
T
T
Mizuki
N
N
Inoko
H
H
Ando
H
H
Ohno
S
S
D000293:Adolescent; D000328:Adult; D000368:Aged; D001483:Base Sequence; D005128:Eye Diseases / Q000235:genetics* / Q000473:pathology; D005260:Female; D005838:Genotype; D005901:Glaucoma / Q000150:complications; D006684:HLA-DR Antigens / Q000235:genetics*; D059811:HLA-DRB1 Chains; D059826:HLA-DRB3 Chains; D006801:Humans; D007429:Intraocular Pressure; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009900:Optic Nerve / Q000473:pathology; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D012150:Polymorphism, Restriction Fragment Length; D012507:Sarcoidosis / Q000235:genetics* / Q000473:pathology
D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains; D059826:HLA-DRB3 Chains