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.
Highlights
Schistosomiasis is the most prevalent water-borne parasitic disease worldwide and remains a major public health problem in many developing countries
We report for the first time that a higher frequency of the Major histocompatibility complex class I chain-related A (MICA) allele*A5 correlated significantly with the development of advanced liver fibrosis in schistosomiasis patients from the Dongting Lake region in Hunan Province, China
The human MICA gene is localized within the HLA class I region of chromosome 6, between MICB and HLA-B, and is known to be highly polymorphic [17]
Summary
Schistosomiasis is the most prevalent water-borne parasitic disease worldwide and remains a major public health problem in many developing countries. The Dongting Lake, located in the north of Hunan Province, is the second largest freshwater lake in China and provides an ideal habitat for Oncomelania snails, the intermediate host for S. japonicum. Sporocysts are generated in the snail and produce infective cercariae that are released from the snail into the surrounding aqueous environment. These free-swimming parasitic larvae secrete a proteolytic enzyme that facilitates penetration of Received August 21, 2011.
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