Study On Relationship Between MICA/B Genetic Polymorphism And Schistosomiasis&Leukemia

Purposes1. Study on characterization of MICA/B genetic polymorphism in a northern Chinese Hunan Han population.2. Study on the relationship between the MICA/B genetic polymorphism and susceptibility to Schistosomiasis infection.3. Study on the relationship between MICA/B genetic polymorphism and susceptibility to leukemia.MethodsGenomic DNA was extracted from fresh peripheral blood leukocytes by WHO recommended standard salting-out method. MICA/B genotypes were determined by using two methods:PCR-sequence-specific primers (PCR-SSP) and PCR-sequence-based typing (PCR-SBT). Allele frequencies as well as MICA and MICB haplotypic variation were analyzed. The relationship between MICA/B gene polymorphism and susceptibility to leukemia and schistosomiasis infection. were studied.ResultsStudy on characterization of MICA/B genetic polymorphism in a northern Chinese Hunan Han populationIn a northern Hunan Han population, eleven MICA alleles were found, among which MICA*010(28.95%), MICA*00801(20.53%) and MICA*002:01(15.79%) were the common alleles. Five MICA-STR(short tandem repeat) alleles were found, among which MICA*A5(37.89%) and MICA*A5.1(21.05%) were predominated, while MICA*A6(7.37%) was with the smallest frequency.In this population, ten MICB alleles were found. The common alleles were MICB*005:02/*010(58.42%), MICB*002:01(10.00%), and MICB*008(7.89%). MICB*012(0.53%) and MICB*019(0.53%) were with the smallest frequency in this population.This study also showed MICA/B gene with high polymorphism in different populations.There were significant differences of allele frequency and allele distribution between this population and other populations. MICA/B alleles distribution in northern Hunan Han population with its unique characteristics.Two kinds of MICA-MICB haplotypes were MIC A*004-MICB*004:01and MICA*010-MICB*005:02/010in significant LD.Study the association of MICA/B polymorphism with SchistosomiasisIn this study, we investigated whether MICA/B polymorphisms were associated with the particularly high rate of Schistosoma parasitic worm infection or severity of disease outcome in the Dongting Lake region of northern Hunan Province, China. Thirteen MICA alleles and five short-tandem repeat (STR) alleles were identified in the health control and the Dongting Lake area population. The frequency of three alleles, MICA*012:01, MICA*017and MICA*027, were higher in healthy controls than in schistosomiasis patients, but the difference was not significantly correlated with susceptibility to S. japonicum infection (Pc>0.05). MICA*A5allele frequency was significantly higher in advanced liver fibrosis groups than slight liver fibrosis groups(Pc<0.05). This study provides the initial evidence that MICA genetic polymorphisms may underlie the severity of liver fibrosis developed in schistosomiasis patients.Ten MICB alleles were identified in the patient group. There were not significant differences in allele frequencies of the MICB gene both between the patients and the control, and between the advanced fibrotic group and the mild fibrotic group. Two kinds of MICA-MICB haplotypes were MICB*008-MICA*002:01and MICB*014-MICA*045in Schistosomiasis infection group.Study on relationship between MICA/B polymorphism and susceptibility to leukemiaEleven MICA alleles, ten MICB alleles and five MICA-STR alleles were identified in leukemia patients. MICA alleles did not show significant differences among the gourps including patient group, health control group and the patient groups with different types of leukemia. MICB*005:02/010allele was less frequently observed in leukemic patients (for MICB*005:02/010:OR=0.416,95%CI:0.270-0.640, Pc=0.0005<0.05), suggesting that MICB*005:02/010may be a protective allele for leukemia.There were not significant differences between any of the MICB alleles and different leukemia subtypes. In patients, four kinds of MICA-MICB haplotypes, including MICB*008-MICA*002:01, MICB*005:03-MICA*009:01, MICA*019-MICB*005:02/010and MICA*045-MICB*014were found in significant LD.Conclusion1. MICA/B gene showed high polymorphism in a northern Hunan Han population. There is significant diference between this population and other populations. But Cluster analysis suggests that northern Hunan Han population is genetically closly related to other Chinese poplations. MICA*012:01is with more frequency in Hunan Han population than other Chinese populations, two kinds of MICA-MICB haplotypes were MICA*004-MICB*004:01and MICA*010-MICB*005:02/010in signific-ant LD.2. MICA/B alleles were not associated with schistosomiasis infection in Hunan Han population in the Dongting Lake region.MICA*A5allele was significantly correlated with advanced liver fibrosis (Pc<0.05).MICB alleles were not associated with schistosomiasis liver fibrosis.3. In Hunan Han population, MICA alleles were not associated with susceptibility to leukemia. MICB*005:02/010allele was found negative correlation with leukemia susceptibility.