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European Journal of Clinical Pharmacology

, Volume 66, Issue 12, pp 1207–1215 | Cite as

Association analysis of SLC30A8 rs13266634 and rs16889462 polymorphisms with type 2 diabetes mellitus and repaglinide response in Chinese patients

  • Qiong Huang
  • Ji-Ye Yin
  • Xing-Ping Dai
  • Jing Wu
  • Xiang Chen
  • Cai-Shu Deng
  • Min Yu
  • Zhi-Cheng Gong
  • Hong-Hao Zhou
  • Zhao-Qian LiuEmail author
Pharmacogenetics

Abstract

Objective

Genome-wide association studies (GWASs) identified that SLC30A8 genetic polymorphism was a risk of type 2 diabetes mellitus (T2DM) in several populations. This study aimed to investigate whether the SLC30A8 rs13266634 and rs16889462 polymorphisms were associated with T2DM susceptibility and repaglinide therapeutic efficacy in Chinese T2DM patients.

Methods

We conducted a case–control study of 443 T2DM patients and 229 healthy volunteers to identify SLC30A8 rs13266634 and rs16889462 genotypes by polymerase chain reaction–restriction fragment length polymorphism (PCR-RFLP) assay. Forty-eight patients were randomly selected and underwent an 8-week repaglinide treatment (3 mg/d). Fasting plasma glucose (FPG), postprandial plasma glucose (PPG), glycated hemoglobin (HbAlc), fasting serum insulin (FINS), postprandial serum insulin (PINS), homeostasis model assessment for insulin resistance (HOMA-IR), serum triglyceride, total cholesterol (TC), low-density lipoprotein-cholesterol (LDL-c) and high-density lipoprotein-cholesterol (HDL-c) were determined before and after repaglinide treatment.

Results

SLC30A8 rs13266634 risk C allele frequency was higher in T2DM patients than in healthy controls (P < 0.05). There was a better repaglinide response on FINS (P < 0.05) and PINS (P < 0.01) in patients with rs13266634 CT+TT genotypes compared with CC genotype carriers. Patients with rs16889462 GA genotype showed an enhanced repaglinide efficacy on FPG (P < 0.01), PPG (P < 0.01) and HbAlc (P < 0.05) compared with GG genotype individuals.

Conclusions

SLC30A8 rs13266634 and rs16889462 polymorphisms were associated with repaglinide therapeutic efficacy in Chinese T2DM patients.

Keywords

SLC30A8 rs13266634 SLC30A8 rs16889462 Genetic polymorphisms Type 2 diabetes mellitus Repaglinide Zinc transporter protein member 8 

Abbreviations

GWASs

genome-wide association studies

SNPs

single nucleotide polymorphisms

T2DM

type 2 diabetes mellitus

PCR-RFLP

polymerase chain reaction–restriction fragment length polymorphism

ZnT-8

zinc transporter protein member 8

SLC30A8

zinc transporter solute carrier family 30 member 8 gene

BMI

body mass index

WHR

waist to hip ratio

FPG

fasting plasma glucose

PPG

postprandial plasma glucose

HbAlc

glycated hemoglobin

FINS

fasting serum insulin

PINS

postprandial serum insulin

HOMA-IR

homeostasis model assessment for insulin resistance

TC

total cholesterol

LDL-c

low-density lipoprotein-cholesterol

HDL-c

high-density lipoprotein-cholesterol

DV

differential value (postadministration minus preadministration)

IFG

impaired fasting glycemia

[Ca2+]i

intracellular free calcium

ABCC8

adenosine triphosphate (ATP)-binding cassette superfamily subfamily C (CFTR/MRP), member 8

KCNJ11

potassium inwardly rectifying channel subfamily J, member 11

VDCC

voltage-dependent calcium channels

Notes

Acknowledgments

We thank all study participants for their cooperation. This work was supported by the National “created a major new drugs”-Science and Technology Major Project (No. 2009ZX09304), the National Natural Science Foundation of China Grants 30572230, 30873089, and by the Hunan Provincial Natural Science Foundation of China Grants 08JJ3058.

Conflict of interest

The authors declare that there is no conflict of interest associated with this manuscript.

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Copyright information

© Springer-Verlag 2010

Authors and Affiliations

  • Qiong Huang
    • 1
  • Ji-Ye Yin
    • 1
  • Xing-Ping Dai
    • 1
  • Jing Wu
    • 2
  • Xiang Chen
    • 3
  • Cai-Shu Deng
    • 4
  • Min Yu
    • 1
  • Zhi-Cheng Gong
    • 1
  • Hong-Hao Zhou
    • 1
  • Zhao-Qian Liu
    • 1
    Email author
  1. 1.Institute of Clinical Pharmacology, Hunan Key Laboratory of PharmacogeneticsCentral South UniversityChangshaPeople’s Republic of China
  2. 2.Department of Endocrinology, The XiangYa HospitalCentral South UniversityChangshaPeople’s Republic of China
  3. 3.Department of Dermatology, The XiangYa HospitalCentral South UniversityChangshaPeople’s Republic of China
  4. 4.Department of PathologyCreighton UniversityOmahaUSA

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