Guja C, Guja Loreta, Nutland Sarah, Rance Helen, Todd J A, Ionescu-Tîrgovişte C
Clinic of Diabetes, Institute of Diabetes, Nutrition and Metabolic Diseases N. Paulescu, Bucharest, Romania.
Rom J Intern Med. 2004;42(2):313-23.
Type 1 diabetes (T1DM) is a common, chronic disease with autoimmune pathogeny, conditioned by genetic factors. Class II HLA DR and DQ and insulin gene polymorphisms encode for most of the T1DM genetic susceptibility. We have previously shown that class I alleles of the insulin gene INS-VNTR locus are strongly associated with T1DM in the Romanian population. The aim of our study was to confirm the contribution of INS-VNTR to T1DM genetic susceptibility in Romania. For this we typed the insulin gene -23HphI A/T polymorphism (an accurate marker for the INS-VNTR alleles) on 219 Romanian T1DM families using Taqman. Allele transmission to diabetics and unaffected siblings was assessed using the Transmission Disequilibrium Test (TDT). We found a significantly increased transmission of -23HphI A allele to diabetics (78.31% transmission, pTDT = 2.4 e-07) which confirms our previous findings. Combined with the data from the first 204 Romanian T1DM families, the transmission of -23HphI A allele to diabetics is almost 80% (79.78%, pTDT = 2.8 e-15). This percentage indicates the same level of predisposition as for the most diabetogenic HLA's. In conclusion, our results indicate an exceptionally strong association of the class I INS-VNTR alleles with T1DM for the Romanian population.
1型糖尿病（T1DM）是一种常见的慢性自身免疫性疾病，受遗传因素影响。II类人类白细胞抗原（HLA）DR和DQ以及胰岛素基因多态性构成了大多数T1DM的遗传易感性。我们之前已经表明，胰岛素基因INS - VNTR位点的I类等位基因与罗马尼亚人群的T1DM密切相关。我们研究的目的是证实INS - VNTR对罗马尼亚T1DM遗传易感性的影响。为此，我们使用Taqman技术对219个罗马尼亚T1DM家庭的胰岛素基因 - 23HphI A/T多态性（INS - VNTR等位基因的精确标记）进行分型。使用传递不平衡检验（TDT）评估等位基因向糖尿病患者及其未患病同胞的传递情况。我们发现 - 23HphI A等位基因向糖尿病患者的传递显著增加（传递率为78.31%，pTDT = 2.4×10⁻⁷），这证实了我们之前的发现。结合前204个罗马尼亚T1DM家庭的数据， - 23HphI A等位基因向糖尿病患者的传递率接近80%（79.78%，pTDT = 2.8×10⁻¹⁵）。这个百分比表明其易感性水平与最具糖尿病致病性的HLA相同。总之，我们的结果表明，对于罗马尼亚人群，I类INS - VNTR等位基因与T1DM存在异常强烈的关联。
