MICA‐STR, HLA‐B haplotypic diversity and linkage disequilibrium in the Hunan Han population of southern China

Abstract

Major histocompatibility complex (MHC) class I chain-related gene A (MICA) is located 46 kb centromeric to HLA-B and encodes a stress-inducible protein. MICA allelic variation is thought to be associated with disease susceptibility and immune response to transplants. This study was aimed to investigate the haplotypic diversity and linkage disequilibrium between human leukocyte antigen (HLA)-B and (GCT)(n) short tandem repeat in exon 5 of MICA gene (MICA-STR) in a southern Chinese Han population. Fifty-eight randomly selected nuclear families with 183 members including 85 unrelated parental samples were collected in Hunan province, southern China. HLA-B generic typing was performed by polymerase chain reaction-sequence-specific priming (PCR-SSP), and samples showing novel HLA-B-MICA-STR linkage were further typed for HLA-B allelic variation by high-resolution PCR-SSP. MICA-STR allelic variation and MICA gene deletion (MICA*Del) were detected by fluorescent PCR-size sequencing and PCR-SSP. Haplotype was determined through family segregation analysis. Statistical analysis was applied to the data of the 85 unrelated parental samples. Nineteen HLA-B specificities and seven MICA-STR allelic variants were observed in 85 unrelated parental samples, the most predominant of which were HLA-B*46, -B60, -B*13, and -B*15, and MICA*A5, MICA*A5.1 and MICA*A4, respectively. Genotype distributions of HLA-B, MICA-STR loci were consistent with Hardy-Weinberg proportions. The HLA-B-MICA-STR haplotypic phases of all 85 unrelated parental samples were unambiguously assigned, which contained 30 kinds of HLA-B, MICA-STR haplotypic combinations, nine of them have not been reported in the literature. Significant positive linkage disequilibria between certain HLA-B and MICA-STR alleles, including HLA-B*13 and MICA*A4, HLA-B*38 and MICA*A9, HLA-B*58 and MICA*A9, HLA-B*46 and MICA*A5, HLA-B*51 and MICA*A6, HLA-B*52 and MICA*A6, and HLA-B60 and MICA*A5.1, were observed. HLA-B*48 was linked to MICA*A5, MICA*A5.1 and MICA*Del. HLA-B*5801-MICA*A10 linkage was found in a family. Our data indicated a high degree of haplotypic diversity and strong linkage disequilibrium between MICA-STR and HLA-B in a southern Chinese Han population, the data will inform future studies on anthropology, donor-recipient HLA matching in clinical transplantation and HLA-linked disease association.

MICA-STR A.4 Is Associated With Slower Hearing Loss Progression in Patients With Ménière’s Disease

“…This lack of replication with the HLA genes has oriented our studies toward the analysis of the association of genes located within this region with polymorphic microsatellites, such as MICA-STR, which has shown LD with genes HLA-B (22). MICA is a member of the nonclassical class I family receptors that displays the greatest degree of polymorphism, and these polymorphisms are associated with a number of diseases related to NK activity (23).…”

MICA genetic polymorphism and HLA-A,C,B,MICA and DRB1 haplotypic variation in a southern Chinese Han population: Identification of two new MICA alleles, MICA*060 and MICA*062

“…HLA-A, C, and B data by generic PCR-SSP have been reported for the majority of the 201 samples [13,14]. In the present study, HLA-DRB1 together with HLA-A, C, and B loci of the remaining samples were typed by PCR-SSP using commercial typing reagents (Genovision, Westchester, PA).…”

Association of HLA genes with Ankylosing Spondylitis in Han Population of eastern China

“…In our study, MICA*A5.1‐related haplotypes D6S2927* 221–D6S2810*350–STR_MICA*A5.1 and D6S2810* 350–STR_MICA*A5.1–D6S2800*136 were also significantly increased in B27‐positive AS patients when compared with B27‐positive controls. However, a supplemental pairwise LD analysis revealed that MICA*A5.1 was in strong LD with HLA‐B60, which was supported in another Chinese population cohort of southern China [27], and it has been confirmed in several different populations that HLA‐B60 acted independently of HLA‐B27 in increasing risk of susceptibility to AS [5, 8, 9]. Apart from STR_MICA in exon 5, MICA gene also displays a remarkable degree of nucleotide variation in exons 2–4, and MICA‐129 met/met genotype in exon 3 was reported in association with Algerian juvenile AS independently of HLA‐B27 [13].…”