Glucose-Raising Genetic Variants in MADD and ADCY5 Impair Conversion of Proinsulin to Insulin
2011

Genetic Variants Affecting Proinsulin to Insulin Conversion

Sample size: 1782 publication Evidence: moderate

Author Information

Author(s): Robert Wagner, Katarzyna Dudziak, Silke A. Herzberg-Schäfer, Fausto Machicao, Norbert Stefan, Harald Staiger, Hans-Ulrich Häring, Andreas Fritsche

Primary Institution: Eberhard Karls University Tübingen

Hypothesis

The study aims to establish metabolic phenotypes for genetic variants associated with fasting glycemia to understand their role in glucose homeostasis.

Conclusion

The study found that specific genetic variants in ADCY5 and MADD are associated with impaired conversion of proinsulin to insulin.

Supporting Evidence

  • The effect alleles of the ADCY5 and MADD SNPs were associated with impaired proinsulin-to-insulin conversion.
  • GLIS3 was nominally associated with impaired proinsulin-to-insulin conversion and insulin secretion.
  • Nominally significant effects on insulin sensitivity were found for MADD and PROX1.

Takeaway

Some genes can make it harder for the body to turn a substance called proinsulin into insulin, which is important for controlling blood sugar.

Methodology

This cross-sectional study involved 1782 non-diabetic volunteers who underwent an oral glucose tolerance test and genotyping for 12 SNPs.

Limitations

The study's cohort includes only subjects of European descent, limiting generalizability, and it is cross-sectional without replication in a different cohort.

Participant Demographics

Participants were non-diabetic individuals of European descent with increased risk for type 2 diabetes.

Statistical Information

P-Value

p=0.0001 for MADD, p=0.002 for ADCY5

Statistical Significance

p<0.05

Digital Object Identifier (DOI)

10.1371/journal.pone.0023639

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