Polymorphism rs11085226 in the gene encoding polypyrimidine tract-binding protein 1 negatively affects glucose-stimulated insulin secretion.
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.
Division of Endocrinology, Diabetology, Angiology, Nephrology and Clinical Chemistry, Department of Internal Medicine, Eberhard Karls University Tübingen, Tübingen, Germany.
Martin
M
Heni
Caroline
C
Ketterer
Robert
R
Wagner
Katarzyna
K
Linder
Anja
A
Böhm
Silke A
SA
Herzberg-Schäfer
Fausto
F
Machicao
Klaus-Peter
KP
Knoch
Andreas
A
Fritsche
Harald
H
Staiger
Hans-Ulrich
HU
Häring
Michele
M
Solimena
D000328:Adult; D005260:Female; D055106:Genome-Wide Association Study; D005858:Germany; D005947:Glucose / Q000378:metabolism*; D005951:Glucose Tolerance Test; D034441:Heterogeneous-Nuclear Ribonucleoproteins / Q000235:genetics / Q000502:physiology*; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D038941:Polypyrimidine Tract-Binding Protein / Q000235:genetics / Q000502:physiology*; D012016:Reference Values
D034441:Heterogeneous-Nuclear Ribonucleoproteins; D007328:Insulin; C450006:PTBP1 protein, human; D038941:Polypyrimidine Tract-Binding Protein; D005947:Glucose