Association between MICA gene A4 allele and acute anterior uveitis in white patients with and without HLA-B27.
OBJECTIVE
Acute anterior uveitis is strongly associated with the HLA-B27 antigen and triggered by the involvement of some external factors. However, it is uncertain whether HLA-B27 itself or other gene(s) near the HLA-B region in a linkage disequilibrium with HLA-B27 predispose to this uveitis. We therefore investigated microsatellite polymorphism in the transmembrane region of the major histocompatibility complex class I chain-related gene A (MICA), located 47 kilobases (kb) on the centromeric side of the HLA-B gene on the short arm of chromosome 6 within 6p21.3.


METHODS
We examined the following patients for MICA gene polymorphism by means of polymerase chain reaction and subsequent automated fragment detection by fluorescent-based technology: 64 (37 HLA-B27-positive and 27 HLA-B27-negative) whites with acute anterior uveitis, 74 (67 HLA-B27-negative and 7 HLA-B27-positive) ethnically matched random controls, and 36 HLA-B27-positive healthy controls.


RESULTS
The microsatellite allele consisting of four repetitions of GCT/AGC (designated A4 allele) was present at the significantly higher phenotype frequency (71.9%) in the patient group than in the ethnically matched random control group (13.5%) (P < .0000001, corrected P < .0000001). The A4 allele was strongly linked to HLA-B27 in a white population. However, the A4 allele was also found at the significantly higher phenotype frequency (37.0%) even in the HLA-B27-negative patient group than in the ethnically matched HLA-B27-negative control group (4.5%) (P = .0086, corrected P = .043).


CONCLUSIONS
These results suggest that the MICA gene itself or other nearby gene(s) linked to the MICA A4 allele may be involved in the development of acute anterior uveitis in a white population.
Goto
K
K
Department of Ophthalmology, Yokohama City University School of Medicine, Yokohama, Japan.
Ota
M
M
Maksymowych
W P
WP
Mizuki
N
N
Yabuki
K
K
Katsuyama
Y
Y
Kimura
M
M
Inoko
H
H
Ohno
S
S
D000208:Acute Disease; D000328:Adult; D000483:Alleles; D004247:DNA / Q000032:analysis; D017931:DNA Primers / Q000737:chemistry; D005260:Female; D008040:Genetic Linkage; D015796:HLA-B27 Antigen / Q000235:genetics*; D015395:Histocompatibility Antigens Class I / Q000235:genetics*; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D018895:Microsatellite Repeats / Q000235:genetics; D010641:Phenotype; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D014606:Uveitis, Anterior / Q000235:genetics*; D044465:White People / Q000235:genetics*
D017931:DNA Primers; D015796:HLA-B27 Antigen; D015395:Histocompatibility Antigens Class I; C099187:MHC class I-related chain A; D008565:Membrane Proteins; D004247:DNA