Worldwide differences in the incidence of type I diabetes are associated with amino acid variation at position 57 of the HLA-DQ beta chain.
Worldwide differences in the incidence of type I diabetes are associated with amino acid variation at position 57 of the HLA-DQ beta chain.
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DOI：
10.1073/pnas.87.19.7370
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发表时间：
1990-10
影响因子：
11.1
通讯作者：
J. Dorman;Ronald E Laporte;R. Stone;M. Trucco
中科院分区：
文献类型：
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作者：
J. Dorman;Ronald E Laporte;R. Stone;M. Trucco
在HLA-DQ β链的57位存在天冬氨酸以外的氨基酸（非Asp-57）与胰岛素依赖性糖尿病（IDDM）的易感性高度相关，而在该位置的天冬氨酸（Asp-57）似乎赋予对该疾病的抗性。我们推测，不同种族和国家间胰岛素依赖型糖尿病发病率的30倍差异与这些等位基因频率的变异有关。糖尿病和非糖尿病个体在五个人群中进行了评估，包括低、中、高风险人群。HLA-DQ β基因型在IDDM组和非糖尿病对照组间的分布差异有统计学意义（P <0.001）。在所有地区，非Asp-57等位基因与IDDM显著相关;非Asp-57纯合子相对于Asp-57纯合子的人群特异性比值比范围为14至111。结合病例对照研究的相对风险信息和人群发病率数据，估计宾夕法尼亚州阿勒格尼县白人的基因型特异性发病率。这些发生率用于预测其余人群的总体发生率，其在发生率登记研究确定的实际发生率的95%置信区间内。这些结果与非Asp-57等位基因分布的人群差异可能解释了IDDM发病率的地理差异的假设一致。
The presence of an amino acid other than aspartic acid at position 57 of the HLA-DQ beta chain (non-Asp-57) is highly associated with susceptibility to insulin-dependent diabetes mellitus (IDDM), whereas an aspartic acid at this position (Asp-57) appears to confer resistance to the disease. We hypothesize that the 30-fold difference in IDDM incidence across racial groups and countries is related to variability in the frequency of these alleles. Diabetic and nondiabetic individuals were evaluated in five populations, including those at low, moderate, and high risk. HLA-DQ beta genotype distributions among the IDDM case groups were markedly different (P less than 0.001), as were those among nondiabetic controls (P less than 0.001). Non-Asp-57 alleles were significantly associated with IDDM in all areas; population-specific odds ratios for non-Asp-57 homozygotes relative to Asp-57 homozygotes ranged from 14 to 111. Relative risk information from the case-control study and population incidence data were combined to estimate genotype-specific incidence rates for the Allegheny County, PA, Caucasians. These rates were used to predict the overall incidence rates in the remaining populations, which were within the 95% confidence intervals of the actual rates established from incidence registries. These results are consistent with the hypothesis that population variation in the distribution of non-Asp-57 alleles may explain much of the geographic variation in IDDM incidence.