Université de Paris, AP-HP, Cochin Hospital, Department of Diabetology, DMU ENDROMED, 27 rue du Faubourg Saint-Jacques, 75014 Paris, France; Université de Paris, BFA, CNRS UMR 8251, 75013 Paris, France; Diabetes Center, University of California San Francisco, San Francisco, CA, USA.
Sorbonne Université, AP-HP, Pitié-Salpêtrière Hospital, Department of Medical Genetics, DMU BioGeM, 47/83 Boulevard de l'Hôpital, 75013 Paris, France; PRISIS Reference Center for Rare Diseases, Paris, France.
Diabetes Res Clin Pract. 2022 Jun;188:109908. doi: 10.1016/j.diabres.2022.109908. Epub 2022 May 6.
Identification of monogenic diabetes (MgD) conveys benefits for patients' care. Algorithms for selecting the patients to be genetically tested have been established in EuroCaucasians, but not in non-EuroCaucasian individuals. We assessed the diagnosis rate, the phenotype of MgD, and the relevance of selection criteria, according to ancestry in patients referred for a suspected MgD.
Seven genes (GCK, HNF1A, HNF4A, HNF1B, ABCC8, KCNJ11, INS) were analyzed in 1975 adult probands (42% non-EuroCaucasians), selected on the absence of diabetes autoantibodies and ≥2 of the following criteria: age ≤40 years and body mass index <30 kg/m at diagnosis, and a family history of diabetes in ≥2 generations.
Pathogenic/likely pathogenic variants were identified in 6.2% of non-EuroCaucasian and 23.6% of EuroCaucasian patients (OR 0.21, [0.16-0.29]). Diagnosis rate was low in all non-EuroCaucasian subgroups (4.1-11.8%). Common causes of MgD (GCK, HNF1A, HNF4A), but not rare causes, were less frequent in non-EuroCaucasians than in EuroCaucasians (4.1%, vs. 21.1%, OR 0.16 [0.11-0.23]). Using ethnicity-specific body mass index cutoffs increased the diagnosis rate in several non-EuroCaucasian subgroups.
The diagnosis rate of MgD is low in non-EuroCaucasian patients, but may be improved by tailoring selection criteria according to patients'ancestry.
鉴定单基因糖尿病（MgD）可使患者受益。已经在欧洲白人中建立了用于选择进行基因检测的患者的算法，但在非欧洲白人中尚未建立。我们评估了根据疑似 MgD 患者的血统，诊断率、MgD 的表型以及选择标准的相关性。
在 1975 名成年患者（42%为非欧洲白人）中分析了 7 个基因（GCK、HNF1A、HNF4A、HNF1B、ABCC8、KCNJ11、INS），这些患者选择的标准为无糖尿病自身抗体和≥2 项以下标准：诊断时年龄≤40 岁且体重指数（BMI）<30kg/m2，且≥2 代家族中有糖尿病病史。
在非欧洲白人患者和欧洲白人患者中分别发现了 6.2%和 23.6%的致病性/可能致病性变异（OR 0.21，[0.16-0.29]）。所有非欧洲白人亚组的诊断率均较低（4.1-11.8%）。非欧洲白人中常见的 MgD 病因（GCK、HNF1A、HNF4A），而非罕见病因，比欧洲白人中更为少见（4.1%，vs. 21.1%，OR 0.16 [0.11-0.23]）。使用特定种族的 BMI 切点可提高几个非欧洲白人亚组的诊断率。
非欧洲白人患者的 MgD 诊断率较低，但可通过根据患者的血统调整选择标准来提高诊断率。
