Distribution of MICA haplotypes in a Chinese Han population Xiuzhang Xu a,,† , Wenjie Xia a,,† , Linwei Tian b , Yangkai Chen a , Haoqiang Ding a , Yuan Shao a , Jing Deng a , Jiali Wang a , Yingfeng Huang c , Sentot Santoso d , Yongshui Fu a, *, Xin Ye a, * a Institute of Blood Transfusion, Guangzhou Blood Center, Guangzhou, 510095 Guangdong, People’s Republic of China b School of Public Health, Chinese University of Hong Kong, Hong Kong, SAR, China c Guangzhou First Municipal People’s Hospital Affiliated to Guangzhou Medical College, Guangzhou, 510090 Guangdong, China d Institute for Clinical Immunology and Transfusion Medicine, Justus-Liebig University, D-35392 Giessen, Germany ARTICLE INFO Article history: Received 27 May 2011 Accepted 25 August 2011 Available online 6 November 2011 Keywords: MICA Distribution Cantonese Han population HLA SBT ABSTRACT The MICA gene encodes nonclassical major histocompatibility complex class I molecules, centromeric to HLA-B and telomeric to HLA-DRB1. The MICA genes are polymorphic. The immune response against MICA may correlate with a decrease in graft survival after transplantation. However, data on the frequency of MICA polymorphisms in different populations are limited. In this study, we determined MICA allelic frequencies in a Han population living in Guangdong Province in south China. A total of 15 MICA alleles were identified using sequence-based typing. The most frequent allele was MICA*010 (22.22%), followed by MICA*002:01(18.56%), MICA*008:01(16.32%), and MICA*019(14.93%). The MICA null gene (MICA*Del) exhibited a frequency of 1.743% in this population. MICA and HLA, MICA–HLA-B, and MICA–HLA-A/HLA-B/HLA-DRB1 haplotype frequencies were estimated. The most common 2-, 3- and 4-locus haplotypes were HLA-B*40:01– MICA*008:01 (13.70%), HLA-A*11:01–B*40:01–MICA*008:01(8.25%), and HLA-A*33:03–B*58:01–DRB1*03: 01–MICA*002:01(5.22%). A new MICA allele, MICA*061, was identified and appears to be evolutionarily related to MICA*012:01. This study provides high-resolution information on the distribution of haplotypes with MICA, HLA-A, HLA-B, and HLA-DRB1 in China. This information should help determine the mechanisms underlying diseases and allotransplant rejection associated with MICA polymorphisms in the southern Chinese Han population.  2012 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved. 1. Introduction Evidence indicates a role of non– human leukocyte antigen (HLA) antibodies in acute and chronic rejection of organ transplant. Non-HLA antigens are classified in alloantigens such as major his- tocompatibility complex class I chain-related genes (MIC) or tissue- specific autoantigens (such as vimentin, cardiac myosin, collagen V, and agrin) [1]. Seven MIC genes have been described; however, only 2, MICA and MICB, are expressed on the cell surface. MICA is encoded by genes located on chromosome 6 (6p21.31), centromeric to HLA-B [2]. MICA is highly polymorphic; more than 77 MICA alleles are officially designated by the Nomenclature Committee of the World Health Organization (WHO) (http://www.ebi.ac.uk/imgt/HLA). MICA is composed of 6 exons encoding for a signal peptide, an extracellular domain (exons 2– 4), a transmembrane region (exon 5), and a cytoplasmic domain (exon 6) and is expressed in blood cells and tissues, including endothelial and epithelial cells [3,4]. Several studies have demonstrated the relevance of MICA alloanti- bodies in acute and chronic rejection of various organs, including heart, renal, and pancreas transplants [5,6]. MICA alloantibodies mediate complement-dependent cytotoxicity in vitro, which may indicate their contribution in complement-mediated organ injury. The Han population represents the largest ethnic group in China. The Han ethnic group can be divided based on northern and southern origin [7,8]. In this article, we report the distribution of MICA alleles and the associated haplotypes with HLA-A/-B/-DR in a Han population living in Guangdong Province of south China. 2. Subjects and methods 2.1. Donors Healthy blood donors (n = 152) born in Guangdong Province were recruited. All donors were Cantonese who had resided in Guangdong Province for more than 3 generations. Blood samples were taken with informed consent. The study group comprised 27.15% women and 72.85% men with an average age of 31.0  8.2 years. All protocols were approved by the Institutional Review Committee of Guangzhou Medical Bureau authorities. * Corresponding authors. E-mail addresses: fuyongshui1969@yahoo.com (Y. Fu); huang_yexin@ yahoo.com.cn (X. Ye). † These authors contributed equally to this work. Human Immunology 73 (2012) 75-79 Contents lists available at SciVerse ScienceDirect 0198-8859/$36.00  2012 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved. doi:10.1016/j.humimm.2011.08.021