Distribution of the most Common Genetic Variants Associated with a Variable Drug Response in the Population of the Republic of Macedonia.

Genetic variation in the regulation, expression and activity of genes coding for Phase I, Phase II drug metabolizing enzymes (DMEs) and drug targets, can be defining factors for the variability in both the effectiveness and occurrence of drug therapy side effects. Information regarding the geographic structure and multi-ethnic distribution of clinically relevant genetic variations is becoming increasingly useful for improving drug therapy and explaining inter-individual and inter-ethnic differences in drug response. This study summarizes our current knowledge about the frequency distribution of the most common allelic variants in three broad gene categories: the Phase I oxidation-cytochrome P450 (CYP450) family (CYP2C9, CYP2C19, CYP3A5, CYP2D6); the Phase II conjugation (GSTT1, SULT1A1; UGT1A1) and drug target (TYMS-TSER, MTHFR and VKORC1) in the population of the Republic of Macedonia and compares the information obtained with data published for other indigenous European populations. Our findings define the population of the Republic of Macedonia as an ethnic group with a highly polymorphic genetic profile. These results add to the evidence regarding the distribution of clinically important variant alleles in DME and drug target genes in populations of European ancestry.

Changes of some humoral immunologic indicators and clinical manifestations of cryoglobulinemia in heroin addicts.

UNLABELLED: Different autoantibodies and immunologic abnormalities have been described in heroin addicts. AIMS: dpending on the route of heroin application in heroin addicts to determine: 1) immunoglobulins: IgA, IgG, IgM; 2) complement (C3, C4); 3) some other autoantibodies RF, anti ß2GP1 fractions: IgA, IgG, IgM, ANA; 4) CIC; 5)monitoring the cryoglobulin presence; 6) clinical manifestations in cryoglobulin positive heroin addicts. A total of 363 heroin addicts were analyzed after previously completed questionnaire; biochemical analyses of blood and urine; creatinine clearance (eC(Cr)) by Cockcroft-Gault formula; proteinuria; 24-hour proteinuria (Uprot/Ucreat); ECG; toxicological analyses; complement (C3, C4); immunoglobulins IgA, IgG, IgM; rheumatoid factor; cryoglobulins; circulating immune complexes; antiphospholipid antibodies (anti ß2GP1: IgA, IgG, IgM); antinuclear antibodies. Male patients were predominating (82.09%). Of them 161 were using intravenous heroin (45.4%). IgA was statistically significantly lower in intravenous heroin addicts. Intravenous heroin addicts contrary to those who inhaled heroin had highly significant levels of IgG, IgM, IgG, antiß2GP1 cryoglobulins; significantly higher mean values of: RF, anti ß2GP1 IgA and IgM. Cryoglobulin positive (CP) heroin addicts compared to cryoglobulin negative (CN) presented significantly more frequently with clinical signs of arthralgia, vasculitis, hematuria; whereas highly significantly were manifested respiratory difficulties, neurological disorders, Raynaud phenomenon, proteinuria, 24-hour proteinuria, highly significantly lower mean values of renal clearance. Intravenous heroin addicts compared to the non-parenteral heroin addicts have shown greater changes in certain parameters of humoral immunity. CP heroin addicts have presented with more frequent clinical manifestations than CN heroin addicts.