The Common HNF1A Variant I27L is a Modifier of Age at Diabetes Diagnosis in HNF1A-MODY Individuals.

2.50
Hdl Handle:
http://hdl.handle.net/11287/620749
Title:
The Common HNF1A Variant I27L is a Modifier of Age at Diabetes Diagnosis in HNF1A-MODY Individuals.
Authors:
Locke, J. M.; Saint-Martin, C.; Laver, T.W.; Patel, K. A.; Wood, A. R.; Sharp, S. A.; Ellard, Sian ( 0000-0002-7620-5526 ) ; Bellanné-Chantelot, C.; Hattersley, Andrew T.; Harries, L. W.; Weedon, M.N.
Abstract:
There is wide variation in the age at diagnosis of diabetes in individuals with Maturity-Onset Diabetes of the Young (MODY) due to a mutation in the HNF1A gene. We hypothesised that common variants at the HNF1A locus (rs1169288, I27L; rs1800574, A98V), which are associated with type 2 diabetes susceptibility, may modify age at diabetes diagnosis in HNF1A-MODY individuals. Meta-analysis of two independent cohorts, comprising 781 HNF1A-MODY individuals, found no significant associations between genotype and age at diagnosis. However after stratifying according to type of mutation (protein-truncating variant (PTV) or missense), we found each 27L allele to be associated with a 1.6 year decrease (95% CI -2.6, -0.7) in age at diagnosis, specifically in the subset (n=444) of HNF1A-MODY individuals with a PTV. The effect size was similar and significant across the two independent cohorts of HNF1A-MODY individuals. We report a robust genetic modifier of HNF1A-MODY age at diagnosis that further illustrates the strong effect of genetic variation within HNF1A upon diabetes phenotype.
Citation:
The Common HNF1A Variant I27L is a Modifier of Age at Diabetes Diagnosis in HNF1A-MODY Individuals. 2018 Diabetes
Publisher:
American Diabetes Association
Journal:
Diabetes
Issue Date:
12-Jun-2018
URI:
http://hdl.handle.net/11287/620749
DOI:
10.2337/db18-0133
PubMed ID:
29895593
Additional Links:
http://diabetes.diabetesjournals.org/cgi/pmidlookup?view=long&pmid=29895593
Type:
Journal Article
Language:
en
ISSN:
1939-327X
Appears in Collections:
Diabetes/Endocrine Services; Molecular Genetics; 2018 RD&E publications

Full metadata record

DC FieldValue Language
dc.contributor.authorLocke, J. M.en
dc.contributor.authorSaint-Martin, C.en
dc.contributor.authorLaver, T.W.en
dc.contributor.authorPatel, K. A.en
dc.contributor.authorWood, A. R.en
dc.contributor.authorSharp, S. A.en
dc.contributor.authorEllard, Sianen
dc.contributor.authorBellanné-Chantelot, C.en
dc.contributor.authorHattersley, Andrew T.en
dc.contributor.authorHarries, L. W.en
dc.contributor.authorWeedon, M.N.en
dc.date.accessioned2018-07-10T11:21:51Z-
dc.date.available2018-07-10T11:21:51Z-
dc.date.issued2018-06-12-
dc.identifier.citationThe Common HNF1A Variant I27L is a Modifier of Age at Diabetes Diagnosis in HNF1A-MODY Individuals. 2018 Diabetesen
dc.identifier.issn1939-327X-
dc.identifier.pmid29895593-
dc.identifier.doi10.2337/db18-0133-
dc.identifier.urihttp://hdl.handle.net/11287/620749-
dc.description.abstractThere is wide variation in the age at diagnosis of diabetes in individuals with Maturity-Onset Diabetes of the Young (MODY) due to a mutation in the HNF1A gene. We hypothesised that common variants at the HNF1A locus (rs1169288, I27L; rs1800574, A98V), which are associated with type 2 diabetes susceptibility, may modify age at diabetes diagnosis in HNF1A-MODY individuals. Meta-analysis of two independent cohorts, comprising 781 HNF1A-MODY individuals, found no significant associations between genotype and age at diagnosis. However after stratifying according to type of mutation (protein-truncating variant (PTV) or missense), we found each 27L allele to be associated with a 1.6 year decrease (95% CI -2.6, -0.7) in age at diagnosis, specifically in the subset (n=444) of HNF1A-MODY individuals with a PTV. The effect size was similar and significant across the two independent cohorts of HNF1A-MODY individuals. We report a robust genetic modifier of HNF1A-MODY age at diagnosis that further illustrates the strong effect of genetic variation within HNF1A upon diabetes phenotype.en
dc.language.isoenen
dc.publisherAmerican Diabetes Associationen
dc.relation.urlhttp://diabetes.diabetesjournals.org/cgi/pmidlookup?view=long&pmid=29895593en
dc.rightsArchived with thanks to Diabetesen
dc.subjectWessex Classification Subject Headings::Endocrinology::Diabetesen
dc.subjectWessex Classification Subject Headings::Oncology. Pathology.::Geneticsen
dc.titleThe Common HNF1A Variant I27L is a Modifier of Age at Diabetes Diagnosis in HNF1A-MODY Individuals.en
dc.typeJournal Articleen
dc.identifier.journalDiabetesen
dc.type.versionIn press (epub ahead of print)en

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