Beijing Key Laboratory of Diabetes Research and Care, Department of Endocrinology, Beijing Tongren Hospital, Capital Medical University, Beijing, China.
Beijing Diabetes Institute, Beijing, China.
Diabet Med. 2021 Feb;38(2):e14456. doi: 10.1111/dme.14456. Epub 2020 Dec 1.
PAX6 is a transcription factor involved in embryonic development of many organs, including the eyes and the pancreas. Mutations of PAX6 gene is the main cause of a rare disease, congenital aniridia (CA). This case-control study aims to investigate the effects of PAX6 mutations on glucose metabolism and insulin secretion in families with CA.
In all, 21 families with CA were screened by Sanger sequencing. Patients with PAX6 mutations and CA (cases) and age-matched healthy family members (controls) were enrolled. Oral glucose tolerance test (OGTT) was performed to detect diabetes or impaired glucose tolerance (IGT). Insulin and proinsulin secretion were evaluated.
Among 21 CA families, heterozygous PAX6 mutations were detected in five families. Among cases (n = 10) from the five families, two were diagnosed with newly identified diabetes and another two were diagnosed with IGT. Among controls (n = 12), two had IGT. The levels of haemoglobin A1c were 36 ± 4 mmol/mol (5.57 ± 0.46%) and 32 ± 5 mmol/L (5.21 ± 0.54%) in the cases and the controls, respectively (p = 0.049). More importantly, levels of proinsulin in the cases were significantly higher than that of the controls, despite similar levels of total insulin. The areas under the curve of proinsulin in the cases (6425 ± 4390) were significantly higher than that of the controls (3709 ± 1769) (p = 0.032).
PAX6 may participate in the production of proinsulin to insulin and heterozygous PAX6 mutations may be associated with glucose metabolism in CA patients.
PAX6 是一种参与许多器官胚胎发育的转录因子，包括眼睛和胰腺。PAX6 基因突变是一种罕见疾病——先天性无虹膜（CA）的主要原因。本病例对照研究旨在探讨 PAX6 基因突变对 CA 患者葡萄糖代谢和胰岛素分泌的影响。
共对 21 个 CA 家系进行 Sanger 测序筛查。纳入携带 PAX6 基因突变和 CA（病例）的患者及年龄匹配的健康家系成员（对照）。行口服葡萄糖耐量试验（OGTT）以检测糖尿病或糖调节受损（IGT）。评估胰岛素和前胰岛素的分泌。
在 21 个 CA 家系中，在 5 个家系中检测到杂合 PAX6 基因突变。在来自这 5 个家系的 10 个病例中，有 2 例被诊断为新发糖尿病，另有 2 例被诊断为 IGT。在 12 个对照中，有 2 例 IGT。病例组的糖化血红蛋白水平为 36±4mmol/mol（5.57±0.46%），对照组为 32±5mmol/L（5.21±0.54%）（p=0.049）。更重要的是，尽管总胰岛素水平相似，但病例组的前胰岛素水平明显高于对照组。病例组的前胰岛素曲线下面积（6425±4390）明显高于对照组（3709±1769）（p=0.032）。
PAX6 可能参与前胰岛素转化为胰岛素的过程，杂合 PAX6 基因突变可能与 CA 患者的葡萄糖代谢有关。
