Skip to main content
Journal cover image

Replication of genome-wide association signals of type 2 diabetes in Han Chinese in a prospective cohort.

Publication ,  Journal Article
Chang, Y-C; Chiu, Y-F; Liu, P-H; Shih, K-C; Lin, M-W; Sheu, WH-H; Quertermous, T; Curb, JD; Hsiung, CA; Lee, W-J; Lee, P-C; Chen, Y-T; Chuang, L-M
Published in: Clin Endocrinol (Oxf)
March 2012

BACKGROUND:   A recent genome-wide association study for type 2 diabetes in Han Chinese identified several novel genetic variants. We investigated their associations with quantitative measures to explore the mechanism by which these variants influence glucose homoeostasis. We also examined whether these variants predict progression to diabetes in a large prospective family based Chinese cohort. METHODS:   Five single nucleotide polymorphisms (SNPs) near the protein tyrosine phosphatase, receptor type, D (PTPRD), SRR, MAF/WWOX, and KCNQ1 genes were genotyped in 1138 subjects of Chinese origin from the Stanford Asia-Pacific Program for Hypertension and Insulin Resistance study. RESULTS:   At baseline, the risk-conferring rs7192960 C allele near the MAF/WWOX genes was associated with lower homoeostasis model assessment of β-cell (HOMA-β) (P = 0·01) and second-phase insulin response in oral glucose tolerance test (OGTT) (P = 0·04). The risk-conferring rs2237897 C alleles in the KCNQ1 gene were associated with higher fasting glucose (P = 0·009), lower HOMA-β (P = 0·03), and lower first-phase insulin response in OGTT (P = 0·03). Over an average follow-up period of 5·43 years, participants with the risk-conferring rs17584499 TT genotype in the PTPRD gene were more likely to progress from nondiabetes to diabetes than were noncarriers (hazard ratio: 8·82, P = 4 × 10(-5) ). The risk-conferring T allele in the PTPRD gene was associated with greater increase in homoeostasis model assessment of insulin resistance (HOMA-IR) (P = 0·04) over time. PTPRD gene expression in human adipose tissues was negatively associated with fasting insulin levels and HOMA-IR. CONCLUSION:   Genetic variants near the KCNQ1 and MAF/WWOX genes are associated with reduced insulin secretion. The PTPRD genetic variant appears to be associated with progression to diabetes in Han Chinese, most likely through increased insulin resistance.

Duke Scholars

Altmetric Attention Stats
Dimensions Citation Stats

Published In

Clin Endocrinol (Oxf)

DOI

EISSN

1365-2265

Publication Date

March 2012

Volume

76

Issue

3

Start / End Page

365 / 372

Location

England

Related Subject Headings

  • WW Domain-Containing Oxidoreductase
  • Tumor Suppressor Proteins
  • Reverse Transcriptase Polymerase Chain Reaction
  • Receptor-Like Protein Tyrosine Phosphatases, Class 2
  • Racemases and Epimerases
  • Proto-Oncogene Proteins c-maf
  • Prospective Studies
  • Polymorphism, Single Nucleotide
  • Oxidoreductases
  • Middle Aged
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Chang, Y.-C., Chiu, Y.-F., Liu, P.-H., Shih, K.-C., Lin, M.-W., Sheu, W.-H., … Chuang, L.-M. (2012). Replication of genome-wide association signals of type 2 diabetes in Han Chinese in a prospective cohort. Clin Endocrinol (Oxf), 76(3), 365–372. https://doi.org/10.1111/j.1365-2265.2011.04175.x
Chang, Yi-Cheng, Yen-Feng Chiu, Pi-Hua Liu, Kuang-Chung Shih, Ming-Wei Lin, Wayne H-H Sheu, Thomas Quertermous, et al. “Replication of genome-wide association signals of type 2 diabetes in Han Chinese in a prospective cohort.Clin Endocrinol (Oxf) 76, no. 3 (March 2012): 365–72. https://doi.org/10.1111/j.1365-2265.2011.04175.x.
Chang Y-C, Chiu Y-F, Liu P-H, Shih K-C, Lin M-W, Sheu WH-H, et al. Replication of genome-wide association signals of type 2 diabetes in Han Chinese in a prospective cohort. Clin Endocrinol (Oxf). 2012 Mar;76(3):365–72.
Chang, Yi-Cheng, et al. “Replication of genome-wide association signals of type 2 diabetes in Han Chinese in a prospective cohort.Clin Endocrinol (Oxf), vol. 76, no. 3, Mar. 2012, pp. 365–72. Pubmed, doi:10.1111/j.1365-2265.2011.04175.x.
Chang Y-C, Chiu Y-F, Liu P-H, Shih K-C, Lin M-W, Sheu WH-H, Quertermous T, Curb JD, Hsiung CA, Lee W-J, Lee P-C, Chen Y-T, Chuang L-M. Replication of genome-wide association signals of type 2 diabetes in Han Chinese in a prospective cohort. Clin Endocrinol (Oxf). 2012 Mar;76(3):365–372.
Journal cover image

Published In

Clin Endocrinol (Oxf)

DOI

EISSN

1365-2265

Publication Date

March 2012

Volume

76

Issue

3

Start / End Page

365 / 372

Location

England

Related Subject Headings

  • WW Domain-Containing Oxidoreductase
  • Tumor Suppressor Proteins
  • Reverse Transcriptase Polymerase Chain Reaction
  • Receptor-Like Protein Tyrosine Phosphatases, Class 2
  • Racemases and Epimerases
  • Proto-Oncogene Proteins c-maf
  • Prospective Studies
  • Polymorphism, Single Nucleotide
  • Oxidoreductases
  • Middle Aged