Association analysis of SLC30A8 rs13266634 and rs16889462 polymorphisms with type 2 diabetes mellitus and repaglinide response in Chinese patients
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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.
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.
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.
SLC30A8 rs13266634 and rs16889462 polymorphisms were associated with repaglinide therapeutic efficacy in Chinese T2DM patients.
KeywordsSLC30A8 rs13266634 SLC30A8 rs16889462 Genetic polymorphisms Type 2 diabetes mellitus Repaglinide Zinc transporter protein member 8
genome-wide association studies
single nucleotide polymorphisms
type 2 diabetes mellitus
polymerase chain reaction–restriction fragment length polymorphism
zinc transporter protein member 8
zinc transporter solute carrier family 30 member 8 gene
body mass index
waist to hip ratio
fasting plasma glucose
postprandial plasma glucose
fasting serum insulin
postprandial serum insulin
homeostasis model assessment for insulin resistance
differential value (postadministration minus preadministration)
impaired fasting glycemia
intracellular free calcium
adenosine triphosphate (ATP)-binding cassette superfamily subfamily C (CFTR/MRP), member 8
potassium inwardly rectifying channel subfamily J, member 11
voltage-dependent calcium channels
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.