RGD Reference Report - Ser1369Ala variant in sulfonylurea receptor gene ABCC8 is associated with antidiabetic efficacy of gliclazide in Chinese type 2 diabetic patients. - Rat Genome Database

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Ser1369Ala variant in sulfonylurea receptor gene ABCC8 is associated with antidiabetic efficacy of gliclazide in Chinese type 2 diabetic patients.

Authors: Feng, Y  Mao, G  Ren, X  Xing, H  Tang, G  Li, Q  Li, X  Sun, L  Yang, J  Ma, W  Wang, X  Xu, X 
Citation: Feng Y, etal., Diabetes Care. 2008 Oct;31(10):1939-44. Epub 2008 Jul 3.
RGD ID: 2301898
Pubmed: PMID:18599530   (View Abstract at PubMed)
PMCID: PMC2551631   (View Article at PubMed Central)
DOI: DOI:10.2337/dc07-2248   (Journal Full-text)

OBJECTIVE: The purpose of this study was to investigate whether genetic variants could influence the antidiabetic efficacy of gliclazide in type 2 diabetic patients. RESEARCH DESIGN AND METHODS: A total of 1,268 type 2 diabetic patients whose diabetes was diagnosed within the past 5 years and who had no recent hypoglycemic treatment were enrolled from 23 hospitals in China. All of the patients were treated with gliclazide for 8 weeks. Fasting and oral glucose tolerance test 2-h plasma glucose, fasting insulin, and A1C were measured at baseline and after 8 weeks of treatment. We used two independent cohorts to test the associations of 25 single nuclear polymorphisms in 11 candidate genes with the antidiabetic efficacy of gliclazide. A general linear regression model was used to test the association with adjustment for important covariates. RESULTS: After 8 weeks of gliclazide therapy, mean fasting plasma glucose (FPG) was reduced from 11.1 mmol/l at baseline to 7.7 mmol/l. In cohort 1, we genotyped all 25 SNPs (n = 661) and found that Ser1369Ala of the ABCC8 gene and rs5210 of the KCNJ11 gene were significantly associated with decreases in FPG (P = 0.002). We further genotyped Ser1369Ala in cohort 2 (n = 607) and confirmed the association identified in cohort 1. In the pooled analysis, compared with subjects with the Ser/Ser genotype, subjects with the Ala/Ala genotype had a 7.7% greater decrease in FPG (P < 0.001), an 11.9% greater decrease in 2-h plasma glucose (P = 0.003), and a 3.5% greater decrease in A1C (P = 0.06) after 8 weeks of treatment with gliclazide. CONCLUSIONS: In two independent cohorts of Chinese type 2 diabetic patients, we found consistent evidence that the Ser1369Ala variant in the ABCC8 gene can influence the antidiabetic efficacy of gliclazide.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
type 2 diabetes mellitus  IAGP 2301898DNA:polymorphism: :p.S1369A (human)RGD 
type 2 diabetes mellitus  ISOABCC8 (Homo sapiens)2301898; 2301898DNA:polymorphism: :p.S1369A (human)RGD 

Objects Annotated

Genes (Rattus norvegicus)
Abcc8  (ATP binding cassette subfamily C member 8)

Genes (Mus musculus)
Abcc8  (ATP-binding cassette, sub-family C member 8)

Genes (Homo sapiens)
ABCC8  (ATP binding cassette subfamily C member 8)


Additional Information