Polymorphic Variants rs3088442 and rs2292334 in the Organic Cation Transporter 3 (OCT3) Gene and Susceptibility Against Type 2 Diabetes: Role of their Interaction

Arch Med Res. 2017 Feb;48(2):162-168. doi: 10.1016/j.arcmed.2017.03.010.

Abstract

Aims: In this study, we investigated whether two common variants (rs3088442G>A and rs2292334G>A) in the organic cation transporter 3 (OCT3) gene, a high-capacity transporter widely expressed in various tissues, affect susceptibility to type 2 diabetes (T2D) in patients newly diagnosed with T2D.

Methods: We performed a study with 150 newly diagnosed patients with T2D and 152 controls. The genetic analyses were performed using the restricted fragment length polymorphism (RFLP) after PCR amplification.

Results: For the rs3088442G>A variant, A allele carriers had a significantly lower odds ratio (OR) vs. GG homozygotes in the BMI <30 kg/m2 group (OR = 0.23, p <0.001) compared with the BMI ≥30 kg/m2 group (OR = 0.67, p = 0.34). When ORs were adjusted for BMI, age, sex, and blood pressure, our findings showed that the overexpression of the A allele of the rs3088442G>A variant was associated with a decreased risk of T2D (OR = 0.016, p <0.001). A Bayesian logistic model revealed that the interaction of two variants studied were significantly associated with a decreased risk of T2D (OR = 0.61, p = 0.03).

Conclusions: The present study has identified the protective effect of the variant rs3088442G>A in the 3'-untranslated region of the OCT3 gene in susceptibility to T2D, and that the protective role is maintained in the presence of risky alleles of the variant rs2292334G>A. The association of the A allele of rs3088442G>A with T2D become weaker in obese people than that of non-obese. If confirmed in other populations, the rs3088442G>A variant as a genetic marker may potentially assist in the identification of individuals at an increased risk of T2D.

Keywords: OCT3; Organic cation transporter; rs2292334G>A; rs3088442G>A; type 2 diabetes.

MeSH terms

  • Alleles
  • Bayes Theorem
  • Case-Control Studies
  • Diabetes Mellitus, Type 2 / genetics*
  • Female
  • Genetic Association Studies
  • Genetic Markers
  • Genetic Predisposition to Disease
  • Heterozygote
  • Homozygote
  • Humans
  • Logistic Models
  • Male
  • Middle Aged
  • Obesity / genetics
  • Odds Ratio
  • Organic Cation Transport Proteins / genetics*
  • Polymorphism, Single Nucleotide

Substances

  • Genetic Markers
  • Organic Cation Transport Proteins
  • solute carrier family 22 (organic cation transporter), member 3