Variant in the Dopamine-4-receptor Gene (DRD4) in Patients with Type 1 Diabetes

IIntroductionBecause dopaminergic signaling pathways are one of the regulators of autoimmunity, we hypothesize that the -521C>T DRD4 gene polymorphism may correlate with the risk of diabetes mellitus type 1 (DM1) and its comorbidities. MethodsThe connection of the -521C>T DRD4 gene polymorphism with the DM1 and its comorbidities as well as the levels of serum pro- and anti-inflammatory markers, lipid profiles and values of monocyte subsets was evaluated. ResultsThe key results of our study are as follows: 1) CC genotype and C allele are associated with a reduced risk of DM1 development (OR = 0.593, p = 0.005 and OR = 0.725, p = 0.003; resp.) whereas TT genotype and T allele are associated with a higher risk of DM1 (OR = 1.408, p = 0.04 and OR = 1.380, p = 0.003; resp.);2) CC genotype is associated with an increased risk of dyslipidemia and retinopathy in diabetic patients (OR = 2.376, p = 0.001 and OR = 2.111, p = 0.01; resp.); 3) CC genotype and C allele carriers had the highest frequency of pro-inflammatory CD16+ monocytes (p = 2*10-4 and 0.04 resp.);4) the DRD4 -521C>T polymorphism modifies the inflammatory status as well as lipid profile in DM1 patients. Discussion/ConclusionOur data imply that the dopaminergic signaling pathways may play an important role in the etiology of DM1 as well as its comorbidities and will provide a new insight into the DM1 risk management. The -521C>T DRD4 gene polymorphism could be considered a genetic marker to predict susceptibility to DM1 as well as retinopathy and dyslipidemia progress in patients with already established disease.