Association between MICA gene A4 allele and acute anterior uveitis in white patients with and without HLA-B27

Am J Ophthalmol. 1998 Sep;126(3):436-41. doi: 10.1016/s0002-9394(98)00100-7.

Abstract

Purpose: 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.

MeSH terms

  • Acute Disease
  • Adult
  • Alleles
  • DNA / analysis
  • DNA Primers / chemistry
  • European Continental Ancestry Group / genetics*
  • Female
  • Genetic Linkage
  • HLA-B27 Antigen / genetics*
  • Histocompatibility Antigens Class I / genetics*
  • Humans
  • Male
  • Membrane Proteins / genetics*
  • Microsatellite Repeats / genetics
  • Phenotype
  • Polymerase Chain Reaction
  • Polymorphism, Genetic
  • Uveitis, Anterior / genetics*

Substances

  • DNA Primers
  • HLA-B27 Antigen
  • Histocompatibility Antigens Class I
  • MHC class I-related chain A
  • Membrane Proteins
  • DNA