Heterozygous PAX6 mutations may lead to hyper-proinsulinaemia and glucose intolerance: A case-control study in families with congenital aniridia.

Abstract

AIM:

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.

METHODS:

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.

RESULTS:

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).

CONCLUSION:

PAX6 may participate in the production of proinsulin to insulin and heterozygous PAX6 mutations may be associated with glucose metabolism in CA patients.

• Authors: Wei Tian, Xiao-Rong Zhu, Chun-Yan Qiao, Ying-Nan Ma, Fang-Yuan Yang, Zhen Zhou, Jian-Ping Feng, Ran Sun, Rong-Rong Xie, Jing Lu, Xi Cao, Jian-Bo Zhou, Jin-Kui Yang
• Journal: Diabetic medicine : a journal of the British Diabetic Association (Diabet Med) Vol. 38 Issue 2 Pg. e14456 (02 2021) ISSN: 1464-5491 [Electronic] England
• PMID: 33169869 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2020 Diabetes UK.

Chemical References

• C-Peptide
• Glycated Hemoglobin A
• Insulin
• PAX6 Transcription Factor
• PAX6 protein, human
• hemoglobin A1c protein, human
• Proinsulin

Topics

• Adult
• Aniridia (genetics)
• C-Peptide (metabolism)
• Case-Control Studies
• Diabetes Mellitus (genetics, metabolism)
• Diabetes Mellitus, Type 2 (genetics, metabolism)
• Female
• Glucose Intolerance (genetics, metabolism)
• Glycated Hemoglobin (metabolism)
• Heterozygote
• Humans
• Insulin (metabolism)
• Male
• Middle Aged
• Mutation
• PAX6 Transcription Factor (genetics)
• Proinsulin (metabolism)