Analysis of Polymorphic Variants of Cholinergic Receptor Genes in Type 2 Diabetes Mellitus

Obesity and addictive eating behaviors represent significant causal factors in the development of type 2 diabetes mellitus. Genes encoding muscarinic and nicotinic receptors have been demonstrated to be significantly associated with a wide range of psychiatric disorders. Consequently, these genes represent potential markers for the study of predisposition to both disturbed eating behavior and type 2 diabetes mellitus (T2DM). A total of 992 DNA samples from individuals with T2DM and 1023 DNA samples from healthy controls were examined. A DEBQ-based assessment of eating behavior 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 = 0.0004, OR = 1.72), CHRNA3 rs1051730 (P = 0.00001, OR = 1.25), CHRM5 rs7162140 (P = 0.051, OR = 1.90), and CHRM1 rs2067477 (P = 0.009, OR = 1.41). An association was shown between the AA haplotype (CHRNA5 rs16969968–CHRNA3 rs1051730) and the AAT haplotype (CHRNA5 rs16969968–CHRNA3 rs1051730–CHRNB4 rs17487223) with development of 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 behavior (P = 0.05, 0.003, 0.015, 0.05 respectively). Additionally, the CHRM1 rs2067477 locus was found to be associated with emotional eating behavior (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 behavior and T2DM.