Cosegregation of MIDD and MODY in a Pedigree: Functional and Clinical Consequences.

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Cervin, Camilla (författare): Lund University,Lunds universitet,Diabetes - klinisk obesitasforskning,Forskargrupper vid Lunds universitet,Diabetes - Clinical Obesity,Lund University Research Groups

Liljeström, Brita (författare)

Tuomi, Tiinamaija (författare)

Heikkinen, Seija (författare)

Tapanainen, Juha S (författare)

Groop, Leif (författare): Lund University,Lunds universitet,Genomik, diabetes och endokrinologi,Forskargrupper vid Lunds universitet,Genomics, Diabetes and Endocrinology,Lund University Research Groups

Cilio, Corrado (författare): Lund University,Lunds universitet,Diabetes - immunovirologi,Forskargrupper vid Lunds universitet,Diabetes - Immunovirology,Lund University Research Groups

(creator_code:org_t)

American Diabetes Association, 2004
2004
Engelska.
Ingår i: Diabetes. - : American Diabetes Association. - 1939-327X .- 0012-1797. ; 53:7, s. 1894-1899

Relaterad länk:: http://www.ncbi.nlm.... (free); visa fler...; http://dx.doi.org/10... (free); http://diabetes.diab...; https://lup.lub.lu.s...; https://doi.org/10.2...; visa färre...

Abstract Ämnesord

Stäng

The aim of this study was characterization of a family carrying two mutations known to cause monogenic forms of diabetes, the M626K mutation in the HNF1α gene (MODY3) and the A3243G in mtDNA. β-Cell function and insulin sensitivity were assessed with the Botnia clamp. Heteroplasmy of the A3243G mutation and variants in type 2 diabetes susceptibility genes were determined, and transcriptional activity, DNA binding, and subcellular localization of mutated HNF1α were studied. Thirteen family members carried the mutation in mtDNA; 6 of them also had the M626K mutation, whereas none had only the M626K mutation. The protective Ala12 allele in peroxisome proliferator–activated receptor (PPAR)γ was present in two nondiabetic individuals. Carriers of both mtDNA and HNF1α mutations showed an earlier age at onset of diabetes than carriers of only the mtDNA mutation (median 22 vs. 45 years) but no clear difference in β-cell function or insulin sensitivity. In vitro, the M626K mutation caused a 53% decrease in transcriptional activity in HeLa cells. The mutated protein showed normal nuclear targeting but increased DNA binding. These data demonstrate that several genetic factors might contribute to diabetes risk, even in families with mtDNA and HNF1α mutations.

Av författaren/redakt...: Cervin, Camilla; Liljeström, Brit ...; Tuomi, Tiinamaij ...; Heikkinen, Seija; Tapanainen, Juha ...; Groop, Leif; visa fler...; Cilio, Corrado; visa färre...

Om ämnet

MEDICIN OCH HÄLSOVETENSKAP: MEDICIN OCH HÄLS ...; och Klinisk medicin; och Endokrinologi oc ...

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