Analysis of the type 2 diabetes-associated single nucleotide polymorphisms in the genes IRS1, KCNJ11, and PPARG2 in type 1 diabetes.
It has been proposed that type 1 and 2 diabetes might share common pathophysiological pathways and, to some extent, genetic background. However, to date there has been no convincing data to establish a molecular genetic link between them. We have genotyped three single nucleotide polymorphisms associated with type 2 diabetes in a large type 1 diabetic family collection of European descent: Gly972Arg in the insulin receptor substrate 1 (IRS1) gene, Glu23Lys in the potassium inwardly-rectifying channel gene (KCNJ11), and Pro12Ala in the peroxisome proliferative-activated receptor gamma2 gene (PPARG2). We were unable to confirm a recently published association of the IRS1 Gly972Arg variant with type 1 diabetes. Moreover, KCNJ11 Glu23Lys showed no association with type 1 diabetes (P > 0.05). However, the PPARG2 Pro12Ala variant showed evidence of association (RR 1.15, 95% CI 1.04-1.28, P = 0.008). Additional studies need to be conducted to confirm this result.
Juvenile Diabetes Research Foundation/Wellcome Trust Diabetes and Inflammation Laboratory, Cambridge Institute for Medical Research, University of Cambridge, Cambridge, U.K.
Christina
C
Eftychi
Joanna M M
JM
Howson
Bryan J
BJ
Barratt
Adrian
A
Vella
Felicity
F
Payne
Deborah J
DJ
Smyth
Rebecca C J
RC
Twells
Neil M
NM
Walker
Helen E
HE
Rance
Eva
E
Tuomilehto-Wolf
Jaakko
J
Tuomilehto
Dag E
DE
Undlien
Kjersti S
KS
Rønningen
Cristian
C
Guja
Constantin
C
Ionescu-Tîirgovişte
David A
DA
Savage
John A
JA
Todd
D000328:Adult; D019943:Amino Acid Substitution; D002170:Canada; D002648:Child; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics*; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics; D005060:Europe; D005260:Female; D006801:Humans; D055504:Insulin Receptor Substrate Proteins; D008297:Male; D010750:Phosphoproteins / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D024661:Potassium Channels, Inwardly Rectifying / Q000235:genetics*; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics*; D000099161:Kcnj11 Channel
D055504:Insulin Receptor Substrate Proteins; D010750:Phosphoproteins; D024661:Potassium Channels, Inwardly Rectifying; D018160:Receptors, Cytoplasmic and Nuclear; D014157:Transcription Factors; D000099161:Kcnj11 Channel; C526292:IRS1 protein, human