title: A SNP in G6PC2 predicts insulin secretion in type 1 diabetes.
abstract: We investigated whether single nucleotide polymorphisms in genes related to glucose metabolism correlate with insulin secretion in type 1 diabetes patients. A cohort of 49 type 1 diabetes patients underwent serial mixed meal tolerance tests to assess insulin secretion. Patients were genotyped for SNPs related to glucose metabolism: CDKAL1 rs7754840, G6PC2 rs560887, HHEX rs1111875, KCNJ11 rs5215. Recently diagnosed patients (<100 days) homozygous for the G allele of G6PC2 had higher area under the curve C-peptide on mixed meal tolerance tests compared to non-homozygous patients (344.8 ± 203.2 vs. 167.9 ± 131.5, p = 0.04). Other SNPs did not correlate with insulin secretion in the new onset period. In a longitudinal survival analysis, homozygosity for the minor allele (A) in G6PC2 predicted more rapid loss of insulin secretion over time. A SNP in the beta cell gene G6PC2 may correlate with preserved insulin secretion in type 1 diabetes.
authors.affiliation: Benaroya Research Institute, 1201 9th Ave., IN-RC, Seattle, WA 98101, USA. ssanda@benaroyaresearch.org
authors.forename: Srinath
authors.initials: S
authors.lastname: Sanda
authors.forename: Shan
authors.initials: S
authors.lastname: Wei
authors.forename: Tessa
authors.initials: T
authors.lastname: Rue
authors.forename: Heather
authors.initials: H
authors.lastname: Shilling
authors.forename: Carla
authors.initials: C
authors.lastname: Greenbaum
mesh_terms: D051360:Cyclin-Dependent Kinase 5 / Q000235:genetics; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics* / Q000378:metabolism*; D005260:Female; D055106:Genome-Wide Association Study; D005838:Genotype; D005952:Glucose-6-Phosphatase / Q000235:genetics*; D018398:Homeodomain Proteins / Q000235:genetics; D006720:Homozygote; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D008297:Male; D020641:Polymorphism, Single Nucleotide; D024661:Potassium Channels, Inwardly Rectifying / Q000235:genetics; D011237:Predictive Value of Tests; D014157:Transcription Factors / Q000235:genetics; D012359:tRNA Methyltransferases; D000099161:Kcnj11 Channel
chemical_list: D051360:Cyclin-Dependent Kinase 5; D005952:Glucose-6-Phosphatase; D018398:Homeodomain Proteins; D007328:Insulin; D024661:Potassium Channels, Inwardly Rectifying; D014157:Transcription Factors; D012359:tRNA Methyltransferases; D000099161:Kcnj11 Channel; C078492:HHEX protein, human; C525110:CDKAL1 protein, human; C492194:G6PC2 protein, human