HLA-class II and class I genotypes among Japanese children with Type 1A diabetes and their families
HLA-class II and class I genotypes among Japanese children with Type 1A diabetes and their families
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DOI：
10.1111/j.1399-5448.2011.00833.x
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发表时间：
2012-02-01
影响因子：
3.4
通讯作者：
Amemiya, Shin
中科院分区：
文献类型：
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作者：
Sugihara, Shigetaka;Ogata, Tsutomu;Amemiya, Shin
目的：确定日本自身免疫性1型糖尿病儿童的HLA-DRB 1、DQB 1、DPB 1、A、C和B基因型。方法：作为全国多中心协作研究的一部分，从37个医疗中心招募了430例GADAb和/或IA-2Ab阳性（1A型）患者。研究人员还分析了83名1A型糖尿病儿童的兄弟姐妹和149名亲子三人组的DNA样本。结果：确定了DRB 1和DQB 1的易感和保护等位基因和单倍型。DPB 1等位基因独特的日本人口和共同的多个种族群体也存在。连锁不平衡（LD）分析表明，易感和保护单倍型。TDT没有发现任何等位基因优先从母亲或父亲传递给1A型儿童。DRB 1 * 09：01-DQB 1 * 03：03的纯合性和DRB 1 * 04：05-DQB 1 * 04：01和DRB 1 * 08：02-DQB 1 * 03：02的杂合性与极高的1A型风险相关。1A型儿童及其父母和兄弟姐妹的比较表明，易感DRB 1-DQB 1单倍型的剂量效应和保护性等位基因对免疫发病机制的影响。DRB 1 * 09：01似乎与学龄前儿童1A型diabetes.Conclusions的早期发病密切相关：本研究表明，日本儿童的HLA-II类和I类基因与1A型糖尿病的特征性关联。TDT没有揭示1A型糖尿病中HLA-II类和I类基因的基因组印记。
Objective: To determine the HLA-DRB1, DQB1, DPB1, A, C, and B genotypes among Japanese children with autoimmune type 1 diabetes.Methods: Four hundred and thirty patients who were GADAb and/ or IA-2Ab-positive (Type 1A) were recruited from 37medical centers as part of a nationwide multicenter collaborative study. DNA samples from 83 siblings of the children with Type 1A diabetes and 149 parent-child trios were also analyzed. A case-control study and a transmission disequilibrium test (TDT) were then performed.Results: The susceptible and protective DRB1 and DQB1 alleles and haplotypes were confirmed. DPB1 alleles unique to the Japanese population and those common to multiple ethnic groups were also present. A linkage disequilibrium (LD) analysis showed both susceptible and protective haplotypes. The TDT did not reveal any alleles that were transmitted preferentially from the mother or father to children with Type 1A. Homozygosity for DRB1* 09: 01-DQB1* 03: 03 and heterozygosity for DRB1* 04: 05-DQB1* 04: 01 and DRB1* 08: 02-DQB1* 03: 02 were associated with an extremely high risk of Type 1A. A comparison of children with Type 1A and their parents and siblings suggested a dose effect of susceptible DRB1-DQB1 haplotypes and an effect of protective alleles on immunological pathogenesis. DRB1* 09: 01 appeared to be strongly associated with an early onset in preschool children with Type 1A diabetes.Conclusions: This study demonstrated the characteristic association of HLA-class II and class I genes with Type 1A diabetes among Japanese children. A TDT did not reveal the genomic imprinting of HLA-class II and class I genes in Type 1A diabetes.