Association of MICA gene polymorphisms with liver fibrosis in schistosomiasis patients in the Dongting Lake region

Abstract

Major histocompatibility complex class I chain-related A (MICA) is a highly polymorphic gene located within the MHC class I region of the human genome. Expressed as a cell surface glycoprotein, MICA modulates immune surveillance by binding to its cognate receptor on natural killer cells, NKG2D, and its genetic polymorphisms have been recently associated with susceptibility to some infectious diseases. We determined whether MICA polymorphisms were associated with the high rate of Schistosoma parasitic worm infection or severity of disease outcome in the Dongting Lake region of Hunan Province, China. Polymerase chain reaction-sequence specific priming (PCR-SSP) and sequencing-based typing (SBT) were applied for high-resolution allele typing of schistosomiasis cases (N = 103, age range = 36.2-80.5 years, 64 males and 39 females) and healthy controls (N = 141, age range = 28.6-73.3 years, 73 males and 68 females). Fourteen MICA alleles and five short-tandem repeat (STR) alleles were identified among the two populations. Three (MICA*012:01/02, MICA*017 and MICA*027) showed a higher frequency in healthy controls than in schistosomiasis patients, but the difference was not significantly correlated with susceptibility to S. japonicum infection (Pc > 0.05). In contrast, higher MICA*A5 allele frequency was significantly correlated with advanced liver fibrosis (Pc < 0.05). Furthermore, the distribution profile of MICA alleles in this Hunan Han population was significantly different from those published for Korean, Thai, American-Caucasian, and Afro-American populations (P < 0.01), but similar to other Han populations within China (P > 0.05). This study provides the initial evidence that MICA genetic polymorphisms may underlie the severity of liver fibrosis occurring in schistosomiasis patients from the Dongting Lake region.

Genetic variation at −1878 (rs2596542) in MICA gene region is associated with chronic hepatitis B virus infection in Saudi Arabian patients

“…MICA is highly polymorphic and is found to be expressed in different cell types such as epithelium, endothelial cells, fibroblasts, keratinocytes and monocytes, in response to cellular stress (Bauer et al, 1999;Groh et al, 1998;Zwirner et al, Experimental andMolecular Pathology 95 (2013) 255-258 1999). Additionally, it has been identified as a potential candidate gene for several autoimmune diseases such as Behcet's disease (Mizuki et al, 1997), type I diabetes (Park et al, 2001), coeliac disease (Woolley et al, 2005) and other diseases such as idiopathic pulmonary fibrosis (Aquino-Galvez et al, 2009), and severe liver fibrosis in schistosomiasis patients (Gong et al, 2012). Several studies have also reported the association of MICA polymorphisms with different types of cancers including HCC (Jiang et al, 2011;Lopez-Vazquez et al, 2004).…”

Significance and Distribution of the Mic a/B Alleles Among the Worldwide Populations

“…The A5 allele is widely distributed across the various Asian, Middle-East and Southern European populations ( Figures: 1 and 2-5). This allele is reported to be associated with Liver fibrosis in Chinese communities [33] . Meanwhile, the Malaysian Chinese community is reported to be susceptible to Nasopharyngeal Carcinoma due to the MICA variations [64].…”

“…Such MIC variations are widely reported in worldwide populations such as Chinese [33,48,49,50], Indian [51], Iranian [52,53], Swedish [54], Finnish [55], Korean [56,57], Spanish [58], Bolivian [59], and Algerian [60]. …”

“…Hence, various approaches were devised to upregulate the MIC expression in the target cells, which would in turn increase the cytotoxicity in tumors [28]. Recently, the polymorphisms and expression of the MHC class I chain(MICA/B)-related alleles are reported to be associated with various complications such as Psoriasis [29], Ocular toxoplasmosis*30+, Behçet's disease [31] 26 Liver disease [32], Liver fibrosis [33], Ankylosing spondylitis [34], Celiac disease [35], HIV infections [36], Autoimmune diseases [37][38][39], and importantly, with Graft rejection [40,41], and numerous cancers [42][43][44][45][46][47].…”

Novel Potential Biomarkers for Opisthorchis viverrini Infection and Associated Cholangiocarcinoma

“…There are a number of studies on the role of MICA in relation to the presence of infectious agents, such viruses, bacteria and parasites. For example, a high level of MICA polymorphisms correlates with advanced liver fibrosis in Schistosoma japonicum infection (35). In addition, it is associated with susceptibility or progression of several infectious diseases such as dengue fever (36), tuberculosis (37) and Chagas disease (38).…”