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HLA class II alleles in Japanese patients with inflammatory bowel disease
S Yoshitake1, A Kimura, M Okada
1Department of Genetics, Medical Institute of Bioregulation, Kyushu University, Fukuoka, Japan.
Insights
This study identifies specific human leukocyte antigen (HLA) class II genes associated with inflammatory bowel diseases (IBD) in the Japanese population. Certain HLA alleles are linked to susceptibility or resistance in Crohn's disease and ulcerative colitis.
Area of Science:
- Immunogenetics
- Gastroenterology
Background:
- The genetic basis of inflammatory bowel diseases (IBD), including Crohn's disease (CD) and ulcerative colitis (UC), is complex.
- Human leukocyte antigen (HLA) class II genes are known to play a role in immune responses and have been implicated in various autoimmune conditions.
Purpose of the Study:
- To investigate the association between specific HLA class II alleles and haplotypes with CD and UC in a Japanese population.
- To identify HLA class II alleles that confer susceptibility or resistance to IBD.
Main Methods:
- DNA analysis of HLA class II genes (DR, DQ, DP alleles) using the polymerase chain reaction-sequence specific oligonucleotide probe method.
- Comparison of allele and haplotype frequencies between 111 CD patients, 81 UC patients, and 525 healthy controls.
- Statistical analysis including relative risk (RR) and corrected p-values (Pc) to determine significant associations.
Main Results:
- DQB1*0402 was positively associated with CD.
- Several HLA alleles, including DRB1*1502, DQA1*0103, and DQB1*06011, were positively associated with UC, while DRB4*0101 and DQA1*0302 were negatively associated.
- Haplotype analysis revealed specific DR-DQ combinations associated with CD and UC susceptibility.
Conclusions:
- In the Japanese population, HLA-linked alleles DQB1*0402 and DRB1*1502 are associated with susceptibility to CD.
- DRB1*1502 is identified as a susceptibility allele for UC.
- These findings contribute to understanding the genetic underpinnings of IBD in specific ethnic groups.
Abstract:
The association of various HLA class II loci with Crohn's disease (CD) and ulcerative colitis (UC) has yet to be fully elucidated. To determine whether there is an association of HLA class II genes (DR, DQ and DP alleles) with inflammatory bowel disease (IBD), HLA class II genes for polymorphisms were analyzed at the DNA level in 111 patients with CD, 81 with UC and 525 healthy controls by the polymerase chain reaction-sequence specific oligonucleotide probe method. Allele and haplotype frequencies were compared between these populations. Results were as follows: 1) the presence of DQB1*0402 (RR=3.90, Pc=0.0001) was positively associated with CD; 2) the presence of DRB1*1502 (RR=4.51, P<1X10(-8)), DRB5*0102 (RR=4.70, Pc<1x10(-8)), DQA1*0103 (RR=3.72, Pc=1x10(-5)), DQB1*06011 (RR=3.78, PC=1x10(-5)), DPA1*0201 (RR=3.23, Pc=0.0001) and DPB1*0901 (RR=4.83, PC<1x10(8)) was positively associated and that of DRB4*0101 (RR=0.20, Pc<1X10(-8)) and DQA1*0302 (RR=0.34, Pc=0.001) negatively associated with UC; 3) haplotype analysis showed a positive association between the presence of DRB1*0410-DQA1*0302-DQB1*0402 and DRB1*0802-DQA1*0401-DQB1*0402 with CD, and a negative association between the presence of DRB1*1502-DQA1*0103-DQB1*06011 and CD, there was no association of DRB1*08032-DQA1*0103-DQB1*06011 with CD; and 4) in UC, a positive association with the presence of DRB1*1502-DQA1*0103-DQB1*06011 was found, but DRB1*08032-DQA1*0103-DQB1*06011 was not associated with it. In conclusion, in CD in the Japanese population, HLA-linked disease susceptibility alleles appear to be DQB1*0402 and DRB1*1502, a disease resistance allele. In UC, DRB1*1502 appears to be a disease susceptibility allele.