Genetic similarities between latent autoimmune diabetes in adults, type 1 diabetes, and type 2 diabetes
Genetic similarities between latent autoimmune diabetes in adults, type 1 diabetes, and type 2 diabetes
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DOI：
10.2337/db07-0299
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发表时间：
2008-05-01
期刊：
影响因子：
7.7
通讯作者：
Groop, Leif
中科院分区：
文献类型：
--
作者：
Cervin, Camilla;Lyssenko, Valeriya;Groop, Leif
成人潜伏性自身免疫性糖尿病（LADA）通常被认为是1型糖尿病的一种缓慢进展的亚型，尽管临床表现更类似于2型糖尿病。研究设计和方法-为了实现这一点，我们在361名LADA、718名1型糖尿病患者和1，676名2型糖尿病患者中研究了LADA是否与1型糖尿病或2型糖尿病的TCF 7L2基因共享HLA基因座或INS VNTR和PTPN 22基因的变异，与2型糖尿病患者相比，LAD-LADA受试者显示HLA-DQB1 * 0201/* 0302基因型的风险频率增加（27 vs. 6.9%; P <1 × 10（-6）），与I型糖尿病的风险频率相似（36%）。此外，LADA受试者的保护性HLA-DQB1 * 0602（3）/X频率高于I型糖尿病患者（8.1%对3.2%，P = 0.003）。rs689的AA基因型（指INS VNTR中的I类等位基因）以及PTPN 22基因中rs2476601的CT/TT基因型在1型糖尿病（分别为P = 3 × 10（-14）和P = 1 × 10（-10））和LADA（分别为P = 0.001和P = 0.002）受试者中均高于对照受试者。值得注意的是，LADA受试者TCF 7L2中rs7903146的2型糖尿病相关CT/TT基因型的频率增加（52.8%; P = 0.03），与2型糖尿病受试者相同（54.1%，P = 3 × 10（-7）），与对照组相比（44.8%）和I型糖尿病受试者结论LADA与I型糖尿病（HLA、INS VNTR和PTPN 22）和2型糖尿病（TCF 7L2）共享遗传特征，这证明将LADA视为两种主要类型糖尿病的混合物是合理的。
OBJECTIVE-Latent autoimmune diabetes in adults (LADA) is often considered a slowly progressing subtype of type 1 diabetes, although the clinical picture more resembles type 2 diabetes. One way to improve classification is to study whether LADA shares genetic features with type 1 and/or type 2 diabetes.RESEARCH DESIGN AND METHODS-To accomplish this we studied whether LADA shares variation in the HLA locus or INS VNTR and PTPN22 genes with type I diabetes or the TCF7L2 gene with type 2 diabetes in 361 LADA, 718 type 1 diabetic, and 1,676 type 2 diabetic patients, as well as 1,704 healthy control subjects from Sweden and Finland.RESULTS-LADA subjects showed, compared with type 2 diabetic patients, increased frequency of risk for the HLA-DQB1 *0201/*0302 genotype (27 vs. 6.9%; P < 1 X 10(-6)), with similar frequency as with type I diabetes (36%). In addition, LADA subjects showed higher frequencies of protective HLA-DQB1 *0602(3)/X than type I diabetic patients (8.1 vs. 3.2%, P = 0.003). The AA genotype of rs689, referring to the class I allele in the INS VNTR, as well as the CT/TT genotypes of rs2476601 in the PTPN22 gene, were increased both in type 1 diabetic (P = 3 X 10(-14) and P = 1 X 10(-10), respectively) and LADA (P = 0.001 and P = 0.002) subjects compared with control subjects. Notably, the frequency of the type 2 diabetes-associated CT/TT genotypes of rs7903146 in the TCF7L2 were increased in LADA subjects (52.8%; P = 0.03), to the same extent as in type 2 diabetic subjects (54.1%, P = 3 X 10(-7)), compared with control subjects (44.8%) and type I diabetic subjects (43.39%).CONCLUSIONS-LADA shares genetic features with both type I (HLA, INS VNTR, and PTPN22) and type 2 (TCF7L2) diabetes, which justifies considering LADA as an admixture of the two major types of diabetes.