Abstract
Type 2 diabetes mellitus (T2DM) is a complex metabolic disease and variations in multispecific membrane transporter functions may affect T2DM development, complications or treatment. In this work we have analyzed the potential effects of a major polymorphism, the Q141K variant of the ABCG2 transporter in T2DM. The ABCG2 protein is a multispecific xeno- and endobiotic transporter, affecting drug metabolism and playing a key role in uric acid extrusion. The ABCG2-Q141K variant, with reduced expression level and function, is present in 15–35% of individuals, depending on the genetic background of the population, and has been shown to significantly affect gout development. Several other diseases, including hypertension, chronic renal failure, and T2DM have also been reported to be associated with high serum uric acid levels, suggesting that ABCG2 may also play a role in these conditions. In this work we have compared relatively small cohorts (n = 203) of T2DM patients (n = 99) and healthy (n = 104) individuals regarding the major laboratory indicators of T2DM and determined the presence of the SNP rs2231142 (C421A), resulting the ABCG2-Q141K protein variant. We found significantly higher blood glucose and HbA1c levels in the T2DM patients carrying the ABCG2-Q141K variant. These findings may emphasize the potential metabolic role of ABCG2 in T2DM and indicate that further research should explore how prevention and treatment of this disease may be affected by the frequent polymorphism of ABCG2.
Highlights
Type 2 diabetes mellitus (T2DM) is one of the most common metabolic disorders, associated with elevated blood glucose levels due to insulin resistance and/or relative insulin deficiency
Genetic SNP analysis We have examined the frequency of the SNP rs2231142, known as C421A, leading to the ABCG2-Q141K polymorphism among the control and the T2DM patients
In the present study we have examined the potential relationship between the presence of the ABCG2-Q141K protein variant and the basic metabolic parameters in T2DM patients, as compared to a group of healthy individuals
Summary
Type 2 diabetes mellitus (T2DM) is one of the most common metabolic disorders, associated with elevated blood glucose levels due to insulin resistance and/or relative insulin deficiency. T2DM, comprising of about 90% of all diabetes cases, is a multifactorial disease, genetic background, lifestyle, hormonal changes, infections or medications may all play a role in disease development, making difficult to establish accurate diagnosis and therapy.
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