Wide distribution of the MICA-MICB null haplotype in East Asians

Stress-inducible MICA (MHC class I chain-related A) is known to bind to NKG2D, which is one of the natural killer (NK) cell receptors, and plays a role in immune surveillance. We have reported that a MICA-MICB null haplotype is in linkage disequilibrium with HLA-B*4801 in the Japanese population. In the haplotype, an approximately 100-kb deletion, including the entire MICA gene, was observed and MICB possessed a premature stop codon. In this study, a multiplex polymerase chain reaction (PCR) method was developed for detecting the MICA deletion. MICB alleles were typed by PCR-single-strand conformation polymorphism (SSCP) method and direct sequencing. The frequency of the MICA-MICB null haplotype was 3.7% on the average, and was strongly associated with HLA-B48 in seven East Asian populations. It was presumed that the stop codon of MICB gene generated after the large-scale deletion. The wide distribution of the null haplotype at polymorphic frequencies suggests that the haplotype has been conservatively maintained because of some selective advantage.