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Polymorphism rs11085226 in the Gene Encoding Polypyrimidine Tract-Binding Protein 1 Negatively Affects Glucose-Stimulated Insulin Secretion
- Source :
- PLoS ONE, Vol 7, Iss 10, p e46154 (2012), PLoS ONE, PLoS ONE 7:e46154 (2012)
- Publication Year :
- 2012
- Publisher :
- Public Library of Science (PLoS), 2012.
-
Abstract
- OBJECTIVE: Polypyrimidine tract-binding protein 1 (PTBP1) promotes stability and translation of mRNAs coding for insulin secretion granule proteins and thereby plays a role in β-cells function. We studied whether common genetic variations within the PTBP1 locus influence insulin secretion, and/or proinsulin conversion. METHODS: We genotyped 1,502 healthy German subjects for four tagging single nucleotide polymorphisms (SNPs) within the PTBP1 locus (rs351974, rs11085226, rs736926, and rs123698) covering 100% of genetic variation with an r(2)≥0.8. The subjects were metabolically characterized by an oral glucose tolerance test with insulin, proinsulin, and C-peptide measurements. A subgroup of 320 subjects also underwent an IVGTT. RESULTS: PTBP1 SNP rs11085226 was nominally associated with lower insulinogenic index and lower cleared insulin response in the OGTT (p≤0.04). The other tested SNPs did not show any association with the analyzed OGTT-derived secretion parameters. In the IVGTT subgroup, SNP rs11085226 was accordingly associated with lower insulin levels within the first ten minutes following glucose injection (p = 0.0103). Furthermore, SNP rs351974 was associated with insulin levels in the IVGTT (p = 0.0108). Upon interrogation of MAGIC HOMA-B data, our rs11085226 result was replicated (MAGIC p = 0.018), but the rs351974 was not. CONCLUSIONS: We conclude that common genetic variation in PTBP1 influences glucose-stimulated insulin secretion. This underlines the importance of PTBP1 for beta cell function in vivo.
- Subjects :
- Male
Mitochondrial Diseases
medicine.medical_treatment
lcsh:Medicine
Genome-wide association study
Heterogeneous-Nuclear Ribonucleoproteins
Endocrinology
Reference Values
Germany
Molecular Cell Biology
Insulin Secretion
Signaling in Cellular Processes
Insulin
lcsh:Science
Proinsulin
Glucose tolerance test
Multidisciplinary
biology
medicine.diagnostic_test
PTBP1
Middle Aged
Medicine
Female
Research Article
Signal Transduction
Polypyrimidine Tract-Binding Protein
Adult
medicine.medical_specialty
Single-nucleotide polymorphism
Glucose Signaling
Polymorphism, Single Nucleotide
Internal medicine
Genetics
medicine
Humans
Polypyrimidine tract-binding protein
Allele
Biology
Genetic Association Studies
Diabetic Endocrinology
Endocrine Physiology
lcsh:R
Human Genetics
Diabetes Mellitus Type 1
Diabetes Mellitus Type 2
Glucose Tolerance Test
Diabetes Mellitus and Deafness
Glucose
biology.protein
lcsh:Q
Genome-Wide Association Study
Subjects
Details
- ISSN :
- 19326203
- Volume :
- 7
- Database :
- OpenAIRE
- Journal :
- PLoS ONE
- Accession number :
- edsair.doi.dedup.....efdfaddce93718d80de2ef206c9fbdfc
- Full Text :
- https://doi.org/10.1371/journal.pone.0046154