Non-class IIHLA gene associated with type 1 diabetes maps to the 240-kb region near HLA-B
Non-class IIHLA gene associated with type 1 diabetes maps to the 240-kb region near HLA-B
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DOI：
10.2337/diabetes.49.12.2217
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发表时间：
2000-12-01
期刊：
影响因子：
7.7
通讯作者：
Ilonen, J
中科院分区：
文献类型：
--
作者：
Nejentsev, S;Gombos, Z;Ilonen, J
一些研究提供证据表明，除了DQ-DR基因外，HLA还含有另一个与1型糖尿病相关的未表征基因pr基因。我们的目的是研究该基因独立于DQ-DR基因的作用，并通过匹配的病例对照研究对其进行定位。研究人员对来自芬兰的1400多名患者和3万名对照组进行了研究。他们只是首先对HLA-DQB1、-DQA1和-DRB1基因的选定等位基因进行基因分型。DR3/4（0404）基因型分为75例患者和181例对照，DR3/4（0401）基因型分为241例患者和354例对照。研究了HLA III类和I类区域的10个微卫星标记（D6S273、TNFa、C12A、STR MICA、MIB、C125、C143、C245、C3211和MOGc）以及HLA- a和HLA- b基因的选定等位基因。在DR3/4（0404）分层组中，我们发现位于靠近HLA-B基因的C12A和C143之间的标记与糖尿病有很强的额外关联。在DR3/4(0404)-和DR3/4(0401)-分层组中进行群体分化试验证实了这一点。我们的数据表明，与1型糖尿病相关的另一个基因位于HLA-B附近240kb的区域。我们排除了STR MICA多态性作为与糖尿病相关的突变。
Several studies provide evidence that in addition to the DQ-DR genes, HLA contains another uncharacterized gene pr genes associated with type 1 diabetes. Our aim was to investigate the effect of this gene independently of the DQ-DR genes' and to localize it with a matched case-control study. More than 1,400 patients and 30,000 control individuals from Finland were studied. They mere first genotyped for the selected alleles of the HLA-DQB1, -DQA1, and -DRB1 genes. For the DR3/4(0404) genotype, 75 patients and 181 control subjects were stratified, and 241 patients and 354 controls were stratified for the DR3/4(0401) genotype. Ten microsatellite markers in the HLA class III and I regions (D6S273, TNFa, C12A, STR MICA, MIB, C125, C143, C245, C3211, and MOGc) and selected alleles of the HLA-A and HLA-B genes were studied. In the DR3/4(0404)-stratified group, we found that markers located between C12A and C143 near the HLA-B gene confer a strong additional diabetes association. This was confirmed by the population differentiation test in both DR3/4(0404)- and DR3/4(0401)-stratified groups. Our data indicate that an additional gene associated with type 1 diabetes is located in the 240-kb region near HLA-B. We excluded STR MICA polymorphism as a mutation responsible for diabetes association.