Genetic Polymorphisms of Carnosine Synthase -1(ATPGD1) and Serum Carnosine Levels in Relation to Cardiovascular Diseases in Iraqi Type 2 Diabetics

Diabetes mellitus (DM) is a metabolic disorder specified by persistent hyperglycemia that occurs when β-cell insulin production became unable to control blood glucose with deterioration of response for insulin. The consequent development of DM complications with increased risk for many diseases caused by damaged variety of biological systems, including blood vessels, eyes, kidneys, heart, and nerves. Carnosine is a natural dipeptide (β-alanyl-L-histidine) expressed in both the central nervous system and periphery, it occurs in several tissues most notably in muscle where they represent an appreciable fraction of the total water-soluble nitrogen-containing compounds. Carnosine is synthesized by a cytosolic amino acid ligase, carnosine synthase-1 (CARNS1; also known as ATP-grasp domain–containing protein 1, ATPGD1; EC 6.3.2.11).Several biological and physiological functions have been attributed to carnosine, such as being an anti-inflammatory and antioxidant agent, antiglycating actions, and as a modulator of mitochondrial metabolism. Carnosine level in human serum is affected by several enzymes like carnosine synthase-1 (responsible of carnosine synthesis),thus any genetic polymorphisms in these enzymes could have an impact on enzymes levels and therefore serum carnosine level with consequent  increased risk for many diseases.
This study was aimed to estimate the occurrence of Carnosine synthase -1 SNP (rs 1790733) on chromosom11 (intron –variant) in Iraqi type 2 diabetics  with and without cardio vascular diseases  and it’s correlation with serum levels of carnosine & carnosine synthase-1  and their  association with CVD as T2DM complication.
 
To achieve this aim Enzyme Linked Immunosorbent Assay (ELISA) specific kits were used to estimate serum levels of carnosine & carnosine synthase-1. High resolution melt technique (HRM) was applied for detecting gene polymorphism of carnosine synthase-1 gene (ATPGD1).
The results showed that gene polymorphism of SNP (rs1790733) increased the chance of CVD in T2DM patients by 84.5%   by its effect to decrease the mean of serum levels of carnosine by decreased carnosine synthase-1 level that may correlate to development of CVD in T2DM patients.