PAX6是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的主要病因,先天性无虹膜(CA)。这项病例对照研究旨在研究PAX6突变对CA家族葡萄糖代谢和胰岛素分泌的影响。
总之,通过Sanger测序筛选了21个患有CA的家庭。招募具有PAX6突变和CA的患者(病例)和年龄匹配的健康家庭成员(对照)。进行口服葡萄糖耐量试验(OGTT)以检测糖尿病或葡萄糖耐量受损(IGT)。评估胰岛素和胰岛素原分泌。
在21个CA家族中,在五个家族中检测到杂合PAX6突变。在五个家庭的病例(n=10)中,其中2人被诊断为新发现的糖尿病,另外2人被诊断为IGT.在对照组(n=12)中,两个有IGT。在病例和对照组中,血红蛋白A1c水平分别为36±4mmol/mol(5.57±0.46%)和32±5mmol/L(5.21±0.54%)。分别(p=0.049)。更重要的是,病例的胰岛素原水平明显高于对照组,尽管总胰岛素水平相似。病例的胰岛素原曲线下面积(6425±4390)明显高于对照组(3709±1769)(p=0.032)。
PAX6可能参与胰岛素原对胰岛素的产生,杂合PAX6突变可能与CA患者的糖代谢有关。
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.