Dissertation > Biological Sciences > Anthropology > Human Genetics

Study on Human Leukocyte Antigen (HLA)-DM Polymorphisms and the Disease Association Analyse with Ankylosing Spondylitis(AS) in the Chinese Han Population

Author LiuRongZeng
Tutor LiuDaZhuang; FengMingLiang
School East China Normal University
Course Biomedical
Keywords Chinese Han population HLA-DM gene frequency haplotype linkagedisequilibrium ankylosing spondylitis disease association
CLC Q987
Type Master's thesis
Year 2012
Downloads 29
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Non-classical HLA-DM plays an important and unique role in the processing and presentation of exogenous antigens. Polymorphisms of certain genes and frequency of alleles in populations may indicate susceptibility to certain diseases. In this study, the analysis of HLA-DMA and HLA-DMB gene polymorphisms and haplotypes in the Chinese Han population was conducted to obtain population genetic data. HLA-DM typing has been performed previously by other groups by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and PCR-sequence specific oligonucleotide probe (PCR-SSOP) techniques. In this study, we established a TaqMan PCR typing method as an alternative to these techniques to survey the frequency of DMA and DMB alleles in the population. In the first part of the study Genotyping was conducted on1000unrelated individuals of Han nationality in south and north China using TaqMan PCR typing. To study the association of SNP or allele with AS susceptibility, the frequencies of SNP and allele of HLA-DM were compared between the patient group and the control group in Chinese Han population.110AS patients and1000unrelated healthy controls were selected in the second part of the study. Seven DMA and DMB single nucleotide polymorphisms (SNPs) sites were analyzed with TaqMan PCR technology in AS cases and healthy controls.Four different DMA alleles and six different DMB alleles were detected from1000unrelated individuals of Han nationality in south and north China. All loci met the Hardy-Weinberg equilibrium principle that both allele and genotype frequencies in a population remain constant. We found that the DMA*01:01(69.35%) and DMB*01:01(52.5%) alleles were more frequent in Han Chinese. Analysis of the haplotypes for two loci for DMA and DMB revealed that a highly significant positive linkage disequilibrium presented for DMA*01:01-DMB*01:02, DMA*01:01-DMB*01:03, DMA*01:01-DMB*01:04, DMA*01:02-DMB*01:01, DMA*01:02-DMB*01:05, DMA*01:03-DMB*01:07and DMA*01:04-DMB*01:01haplotypes. Analysis of haplotypes for four loci associated with antigen processing (DMA-DMB-TAP1-TAP2) showed a highly significant linkage disequilibrium in DMA*01:01-DMB*01:04-TAP1*02:01:01-TAP2*01:02, DMA*01:02-DMB*01:05-TAP1*01:01-TAP2*01:01and DMA*01:01-DMB*01:03-TAP1*04:01-TAP2*01:01haplotypes. The comparison between the Chinese Han population and non-Chinese populations showed that no significant differences were found at the HLA-DMA locus in the Chinese Han population compared with people of German nationality, while significant differences presented when compared with Turks, American Caucasians, Japanese, French and Italians nationalities. However, at the HLA-DMB locus, highly significant differences presented in the Chinese Han population compared with Germans and Italians. This study lays the foundations for further disease association analyses.In the second part of the research, we found that the allele frequency of DMA*01:02(19.55%) in AS cases was significantly lower than that in healthy controls (28.05%), and the haplotype frequency ofDMA*01:02-DMB*01:01(17.51%)in AS cases was also significantly lower than that in healthy controls (26.87%), the distributions of DMA p496and DMB p590SNP alleles, the DMA*01:02allele and the DMA*01:02-DMB*01:01haplotype frequencies were significantly different between AS cases and healthy controls (p<0.05). Therefore, the DMA*01:02allele and the DMA*01:02-DMB*01:01haplotype appeared to confer protection in AS. In an attempt to justify the association detected and to achieve further insight into the genetic function, future work is still required.

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