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Capture of type 1 diabetes-susceptible HLA DR-DQ haplotypes in Japanese subjects using a tag single nucleotide polymorphism.

ABSTRACT: OBJECTIVE: To identify type 1 diabetes-susceptible HLA DR-DQ haplotypes using tag single nucleotide polymorphisms (SNPs) and to estimate the disease risk using these tag SNPs. RESEARCH DESIGN AND METHODS: Five tag SNPs were typed in a total of 211 Japanese subjects including 201 patients with type 1 diabetes who had already been typed for HLA-DRB1, -DQA1, and -DQB1 alleles and 300 control subjects. RESULTS: Tag SNP rs2395185 captured haplotypes involving all DR4 specificities and DR9 specificity with a sensitivity of 98.5% and specificity of 94.9%. Using the T allele of rs2395185, we obtained an odds ratio (95% CI) of 2.87 (2.21-3.74) for type 1 diabetes. In addition, rs3129888 captured haplotypes involving HLA-DRB1*0802 with a sensitivity of 92.3% and specificity of 98.9%. CONCLUSIONS: Typing of two tag SNPs (rs2395185 and rs3129888) may be useful for the screening of Japanese subjects at genetic risk of type 1 diabetes.

SUBMITTER: Nakanishi K

PROVIDER: S-EPMC2797963 | biostudies-literature | 2010 Jan

REPOSITORIES: biostudies-literature

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Capture of type 1 diabetes-susceptible HLA DR-DQ haplotypes in Japanese subjects using a tag single nucleotide polymorphism.

Nakanishi Koji K Shima Yukio Y

Diabetes care 20091016 1

<h4>Objective</h4>To identify type 1 diabetes-susceptible HLA DR-DQ haplotypes using tag single nucleotide polymorphisms (SNPs) and to estimate the disease risk using these tag SNPs.<h4>Research design and methods</h4>Five tag SNPs were typed in a total of 211 Japanese subjects including 201 patients with type 1 diabetes who had already been typed for HLA-DRB1, -DQA1, and -DQB1 alleles and 300 control subjects.<h4>Results</h4>Tag SNP rs2395185 captured haplotypes involving all DR4 specificities ...[more]

PMID: 19837788

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Project description:BACKGROUND:Asthma afflicts 6% to 8% of the United States population, and severe asthma represents approximately 10% of asthmatic patients. Several epidemiologic studies in the United States and Europe have linked Alternaria sensitivity to both persistence and severity of asthma. In order to begin to understand genetic risk factors underlying Alternaria sensitivity and asthma, in these studies we examined T cell responses to Alternaria antigens, HLA Class II restriction and HLA-DQ protection in children with severe asthma. METHODS:Sixty children with Alternaria-sensitive moderate-severe asthma were compared to 49 children with Alternaria-sensitive mild asthma. We examined HLA-DR and HLA-DQ frequencies in Alternaria-sensitive asthmatic by HLA typing. To determine ratios of Th1/Th2 Alternaria-specific T-cells, cultures were stimulated in media alone, Alternaria alternata extract and Alt a1. Sensitivity to IL-4 stimulation was measured by up-regulation of CD23 on B cells. RESULTS:Children with Alternaria-sensitive moderate-severe asthma trended to have increased sensitivities to Cladosporium (46% versus 35%), to Aspergillus (43% versus 28%), and significantly increased sensitivities to trees (78% versus 57%) and to weeds (68% versus 48%). The IL-4RA ile75val polymorphism was significantly increased in Alternaria-sensitive moderate-severe asthmatics, 83% (0.627 allele frequency) compared to Alternaria-sensitive mild asthmatics, 57% (0.388 allele frequency). This was associated with increased sensitivity to IL-4 stimulation measured by significantly increased IL-4 stimulated CD23 expression on CD19+ and CD86+CD19+ B cells of Alternaria-sensitive moderate-severe asthmatics. IL-5 and IL-13 synthesis was significantly increased in Alternaria-sensitive moderate-severe asthmatics compared to mild asthmatics to Alternaria extract and Alt a1 stimulation. The frequency of HLA-DQB1*03 allele was significantly decreased in Alternaria-sensitive moderate-severe asthmatics compared to mild asthmatics, 39% versus 63%, with significantly decreased allele frequency, 0.220 versus 0.398. SUMMARY:In children with Alternaria-sensitive moderate severe asthma, there was an increased Th2 response to Alternaria stimulation and increased sensitivity to IL-4 stimulation. This skewing towards a Th2 response was associated with an increased frequency of the IL-4RA ile75val polymorphism. In evaluating the HLA association, there was a decreased frequency of HLA-DQB1*03 in Alternaria-sensitive moderate severe asthmatic children consistent with previous studies suggest that HLA-DQB1*03 may be protective against the development of mold-sensitive severe asthma.

Dataset Information

Capture of type 1 diabetes-susceptible HLA DR-DQ haplotypes in Japanese subjects using a tag single nucleotide polymorphism.

Publications

Capture of type 1 diabetes-susceptible HLA DR-DQ haplotypes in Japanese subjects using a tag single nucleotide polymorphism.

Similar Datasets

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