I27L 常见变异是 HNF1A-MODY 个体中糖尿病诊断年龄的修饰因子。
The Common Variant I27L Is a Modifier of Age at Diabetes Diagnosis in Individuals With HNF1A-MODY.
机构信息
Institute of Biomedical and Clinical Science, University of Exeter Medical School, University of Exeter, Exeter, U.K.
Department of Genetics, Pitié-Salpétrière Hospital, Assistance Publique-Hôpitaux de Paris, and Pierre et Marie Curie University, Paris, France.
出版信息
Diabetes. 2018 Sep;67(9):1903-1907. doi: 10.2337/db18-0133. Epub 2018 Jun 12.
There is wide variation in the age at diagnosis of diabetes in individuals with maturity-onset diabetes of the young (MODY) due to a mutation in the gene. We hypothesized that common variants at the locus (rs1169288 [I27L], rs1800574 [A98V]), which are associated with type 2 diabetes susceptibility, may modify age at diabetes diagnosis in individuals with HNF1A-MODY. Meta-analysis of two independent cohorts, comprising 781 individuals with HNF1A-MODY, found no significant associations between genotype and age at diagnosis. However after stratifying according to type of mutation (protein-truncating variant [PTV] or missense), we found each 27L allele to be associated with a 1.6-year decrease (95% CI -2.6, -0.7) in age at diagnosis, specifically in the subset ( = 444) of individuals with a PTV. The effect size was similar and significant across the two independent cohorts of individuals with HNF1A-MODY. We report a robust genetic modifier of HNF1A-MODY age at diagnosis that further illustrates the strong effect of genetic variation within upon diabetes phenotype.
由于基因中的突变，年轻起病的成年型糖尿病患者（MODY）的发病年龄存在广泛差异。我们假设，与 2 型糖尿病易感性相关的 基因座（rs1169288 [I27L]、rs1800574 [A98V]）的常见变异可能会改变 HNF1A-MODY 患者的糖尿病诊断年龄。对两个独立队列的荟萃分析，共包含 781 名 HNF1A-MODY 患者，发现基因型与诊断年龄之间没有显著关联。然而，根据突变类型（蛋白截断变异体 [PTV] 或错义）进行分层后，我们发现每个 27L 等位基因与诊断年龄降低 1.6 岁（95%CI-2.6，-0.7）相关，特别是在 PTV 患者亚组（=444 名）中。这种效应大小在两个独立的 HNF1A-MODY 患者队列中相似且显著。我们报告了 HNF1A-MODY 诊断年龄的一个稳健的遗传修饰因子，进一步说明了 内遗传变异对糖尿病表型的强烈影响。
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