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

  • Pharmacogenetics
  • Published:
European Journal of Clinical Pharmacology Aims and scope Submit manuscript

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.

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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

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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.

Author information

Authors and Affiliations

  1. Institute of Clinical Pharmacology, Hunan Key Laboratory of Pharmacogenetics, Central South University, Changsha, Hunan, 410078, People’s Republic of China

    Qiong Huang, Ji-Ye Yin, Xing-Ping Dai, Min Yu, Zhi-Cheng Gong, Hong-Hao Zhou & Zhao-Qian Liu

  2. Department of Endocrinology, The XiangYa Hospital, Central South University, Changsha, Hunan, 410008, People’s Republic of China

    Jing Wu

  3. Department of Dermatology, The XiangYa Hospital, Central South University, Changsha, Hunan, 410008, People’s Republic of China

    Xiang Chen

  4. Department of Pathology, Creighton University, Omaha, NE, 68131, USA

    Cai-Shu Deng

Authors
  1. Qiong Huang
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  2. Ji-Ye Yin
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  3. Xing-Ping Dai
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  4. Jing Wu
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  5. Xiang Chen
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  7. Min Yu
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  8. Zhi-Cheng Gong
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  9. Hong-Hao Zhou
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  10. Zhao-Qian Liu
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Corresponding author

Correspondence to Zhao-Qian Liu.

Additional information

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 the Hunan Provincial Natural Science Foundation of China Grants 08JJ3058.

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Huang, Q., Yin, JY., Dai, XP. et al. Association analysis of SLC30A8 rs13266634 and rs16889462 polymorphisms with type 2 diabetes mellitus and repaglinide response in Chinese patients. Eur J Clin Pharmacol 66, 1207–1215 (2010). https://doi.org/10.1007/s00228-010-0882-6

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  • DOI: https://doi.org/10.1007/s00228-010-0882-6

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