Abdolkarim Mahrooz1, Ahad Alizadeh2, Mohammad Bagher Hashemi-Soteh3, Maryam Ghaffari-Cherati4, Seyyedeh Raheleh Hosseyni-Talei4. 1. Immunogenetic Research Center, Mazandaran University of Medical Sciences, Sari, Iran; Diabetes Research Center, Imam Teaching Hospital, Mazandaran University of Medical Sciences, Sari, Iran; Department of Clinical Biochemistry and Genetics, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran. Electronic address: kmahrooz2@gmail.com. 2. Department of Epidemiology and Reproductive Health, Reproductive Epidemiology Research Center, Royan Institute for Reproductive Biomedicine, ACECR, Tehran, Iran. 3. Immunogenetic Research Center, Mazandaran University of Medical Sciences, Sari, Iran; Department of Clinical Biochemistry and Genetics, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran. 4. Department of Clinical Biochemistry and Genetics, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran.
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.
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 obesepeople 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.
Authors: Zulfan Zazuli; Naut J C B Duin; Katja Jansen; Susanne J H Vijverberg; Anke H Maitland-van der Zee; Rosalinde Masereeuw Journal: Int J Mol Sci Date: 2020-09-10 Impact factor: 5.923