Variation in the Dopamine-4-Receptor Gene in Patients with Type 1 Diabetes

INTRODUCTION: Because dopaminergic signaling pathways are one of the regulators of autoimmunity, we hypothesize that the −521C>T DRD4 gene polymorphism may associate with the risk of diabetes mellitus type 1 (DM1) and its comorbidities. METHODS: In this case-control study, we have examined 300 patients with DM1 in comparison to 300 healthy age-matched controls. Utilizing the amplification refractory mutation system-polymerase chain reaction method, we have analyzed the −521C>T polymorphism of dopamine D4 receptor-encoding gene. Obtained results have been evaluated according to diabetes comorbidities, inflammatory markers, CD14(++)CD16(−), and CD14(+)CD16(+) monocyte subsets as well as lipid profile. RESULTS: The 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, respectively), 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, respectively); (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, respectively); (3) CC genotype and C allele carriers had the highest frequency of pro-inflammatory CD16(+) monocytes (p = 2*10(−4) and 0.04, respectively); (4) the DRD4 −521C>T polymorphism modifies the inflammatory status as well as lipid profile in DM1 patients. CONCLUSION: Our 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.