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

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Abstract
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.