Analysis of polymorphic variants of cholinergic receptor genes in type 2 diabetes mellitus

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Abstract

Obesity and addictive eating behaviours represent significant causal factors in the development of type 2 diabetes mellitus. Genes encoding muscarinic and nicotinic receptors have been demonstrated to be significant associated with a wide range of psychiatric disorders. Consequently, these genes represent potential markers for the study of predisposition to both disturbed eating behaviour and type 2 diabetes mellitus (T2DM). A total of 992 DNA samples from individuals with T2DM and 1,023 DNA samples from healthy controls were examined. A DEBQ-based assessment of eating behaviour was conducted. The following polymorphic loci were investigated by real-time PCR: CHRNA5 (rs16969968), CHRNA3 (rs1051730), CHRNB4 (rs17487223), CHRM4 (rs206748), CHRNA3 (rs578776), CHRM5 (rs7162140), CHRM1 (rs2067477), CHRNA7 (rs3826029). The present study found an association between the T2DM and the following genetic variants: CHRNA5 rs16969968 (P = 0.00001, OR = 1.72), CHRNA3 rs1051730 (P = 0.00001, OR = 1.812), CHRM5 rs7162140 (P = 0.051, OR = 1.90), and CHRM1 rs2067477 (P = 0.003, OR = 1.41). It was shown an association between the AA haplotype (CHRNA5 rs16969968 – CHRNA3 rs1051730) and the AAT haplotype (CHRNA5 rs16969968 – CHRNA3 rs1051730 – CHRNB4 rs17487223) with the T2DM (P = 0.0004, OR = 1.37; P = 0.00005, OR = 1.34). The CHRNA3 rs578776, CHRNA7 rs3826029, CHRM5 rs7162140 and CHRM1 rs2067477 loci were found to be associated with Restrictive eating behaviour (P = 0.05, 0.003, 0.015, 0.05 respectively). Additionally, the CHRM1 rs2067477 locus was found to be associated with Emotional eating behaviour (P = 0.014), while the CHRNA5 rs16969968 and CHRNB4 rs17487223 gene polymorphisms were found to be associated with External eating behavior (P = 0.05, P = 0.036). The study revealed an association between polymorphic variants of the studied genes and both disturbed eating behaviour and T2DM.

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About the authors

O. V. Kochetova

Ufa Federal Research Centre of the Russian Academy of Sciences; Bashkir State Medical University

Email: Olga_MK78@mail.ru

Institute of Biochemistry and Genetics

Russian Federation, Ufa; Ufa

D. Sh. Avsaleydiniva

Bashkir State Medical University

Email: Olga_MK78@mail.ru
Russian Federation, Ufa

T. M. Kochetova

Bashkir State Medical University

Email: Olga_MK78@mail.ru
Russian Federation, Ufa

L. Z. Akhmadishina

Ufa Federal Research Centre of the Russian Academy of Sciences

Email: Olga_MK78@mail.ru

Institute of Biochemistry and Genetics

Russian Federation, Ufa

G. F. Korytina

Ufa Federal Research Centre of the Russian Academy of Sciences; Bashkir State Medical University

Author for correspondence.
Email: Olga_MK78@mail.ru

Institute of Biochemistry and Genetics

Russian Federation, Ufa; Ufa

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2. Fig. 1. ROC curves for assessing the prognostic ability of regression models for T2DM. AUC – area under the curve. Model 1 includes all studied genes (AUC = 0.604, 95% CI 0.577–0.631; P = 1.25 × 10–13, sensitivity – 78%, specificity – 40%). Model 2 includes all studied genes and adjustments for sex (AUC = 0.725, 95% CI 0.701–0.749; P = 6.4 × 10–58, sensitivity – 76%, specificity – 63%).

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