A single nucleotide variant in HNF-1β is associated with maturity-onset diabetes of the young in a large Chinese family

Zhou, P. et al. (2016) A single nucleotide variant in HNF-1β is associated with maturity-onset diabetes of the young in a large Chinese family. Iranian Journal of Public Health, 45(2), pp. 170-178. (PMID:27114981) (PMCID:PMC4841871)

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Background: Maturity-onset diabetes of the young (MODY) is a heterogeneous entity of monogenic disorders characterized by autosomal dominant inheritance. Eleven genes were related, including HNF4α, GCK, HNF1α, IPF1, and HNF-1β, and various mutations are being reported. Methods: To help the overall understanding of MODY-related pathologic mutations, we studied a large MODY family found in 2012, in Shandong, China, which contained 9 patients over 3 generations. DNA was extracted from the periphery blood samples of (i) 9 affected members, (ii) 17 unaffected members, and (iii) 1000 healthy controls. Three pooled samples were obtained by mixing equal quantity of DNA of each individual within the each group. Totally 400 microsatellite markers across the whole genome were genotyped by capillary electrophoresis. The known MODY-related gene near the identified marker was sequenced to look for putative risk variants. Results: Allelic frequency of marker D17S798 on chromosome 17q11.2 were significantly different (P<0.001) between the affected vs. unaffected members and the affected vs. healthy controls, but not between the unaffected members vs. healthy controls. MODY5-related gene, hepatocyte nuclear factor-1β (HNF-1β) on 17q12 near D17S798 became the candidate gene. A single nucleotide variant (SNV) of C77T in the non-coding area of exon 1 of HNF-1β was found to be related to MODY5. Conclusion: This novel SNV of HNF-1β contributes to the diabetes development in the family through regulating gene expression most likely. The findings help presymptomatic diagnosis, and imply that mutations in the non-coding areas, as well as in the exons, play roles in the etiology of MODY.

Item Type:Articles
Glasgow Author(s) Enlighten ID:Campbell, Dr Desmond
Authors: Zhou, P., Wei, R., Guo, Z., Zhu, H., Campbell, D., Li, Q., Xu, X., Wang, J., Luan, M., Chen, X., and Chen, G.
College/School:College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health
Journal Name:Iranian Journal of Public Health
Publisher:Tehran University of Medical Sciences
ISSN (Online):2251-6093
Copyright Holders:Copyright © 2015 The Authors
First Published:First published in Iranian Journal of Public Health 45(2):170-178
Publisher Policy:Reproduced under a creative commons license

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