Increased all-cause and cardiovascular mortality in monogenic diabetes as a result of mutations in the HNF1A gene

Diabet Med. 2010 Feb;27(2):157-61. doi: 10.1111/j.1464-5491.2009.02913.x.

Abstract

Aims: To investigate all-cause and cardiovascular mortality in subjects with diabetes caused by a mutation in the hepatocyte nuclear factor 1alpha gene (HNF1A).

Methods: We identified 39 British families with HNF1A mutations. Consenting individuals were asked details of age and cause of death of parents and siblings. Copies of death certificates were requested from the family or were obtained via the Offices for National Statistics.

Results: Data were collated on 241 control subjects and 153 mutation carriers. Of those who died, 66% of mutation carriers died from a cardiovascular-related illness compared with 43% of control subjects (P = 0.02). Family members with HNF1A mutations died at a younger age than familial control subjects [all-cause hazard ratio, adjusting for sex and smoking status: 1.9 (95% confidence interval 1.2, 2.9, P = 0.006; cardiovascular hazard ratio: 2.3, confidence interval 1.3, 4.2, P = 0.006)].

Conclusions: We have shown that individuals known to have diabetes caused by a mutation in the HNF1A gene have an increased risk of cardiovascular mortality compared with their unaffected family members. As with other forms of diabetes, consideration should be given to early statin therapy despite a seemingly protective lipid profile.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Cardiovascular Diseases / etiology
  • Cardiovascular Diseases / mortality*
  • DNA Mutational Analysis
  • Diabetes Mellitus, Type 1 / complications
  • Diabetes Mellitus, Type 1 / genetics*
  • Diabetes Mellitus, Type 1 / mortality
  • Diabetes Mellitus, Type 2 / complications
  • Diabetes Mellitus, Type 2 / genetics*
  • Diabetes Mellitus, Type 2 / mortality
  • Family
  • Female
  • Hepatocyte Nuclear Factor 1-alpha / genetics*
  • Humans
  • Male
  • Middle Aged
  • Mortality*
  • Mutation / genetics*
  • Risk
  • Sequence Analysis, DNA
  • Survival Analysis

Substances

  • HNF1A protein, human
  • Hepatocyte Nuclear Factor 1-alpha