ABSTRACT
OBJECTIVE: Aim: The study aims to investigate the effect of solute carriers organic anions transporters 1B1 (SLCO1B1) gene polymorphisms rs4149056, rs2306283, rs55901008, and rs729559745 in a sample of patients with dyslipidemia, and relate it to atorvastatin response and associated myopathy. PATIENTS AND METHODS: Materials and Methods: A cross sectional enrolled 200 patients both males and females of Arabic race, Iraqi nationality aged between 30-65 years. The patients were divided into two groups: Group 1 (Atorvastatin responders and tolerant), Group 2 (Atorvastatin non responder and intolerant). Blood samples collected from the patients for biochemical studies and analyzed statistically by Student T-test and Chi-square, and DNA extracted for polymerase chains reactions (PCR). RESULTS: Results: The results showed insignificant association P≥0.05 between the demographic characteristics of the study population with different genotypes, and significant difference P<0.05 in the biochemical parameters regarding (T-cholesterol, triglycerides, low density lipoproteins, and Creatine kinase-MM) when comparing the two groups. Odds ratio (OR) with confidence intervals CI (95%) used to evaluate the risk association to develop myopathy and poor response to atorvastatin therapy show relevant association for CC and CT genotype of rs4149056, while rs2306283 GG genotype show low association, also rs55901008 show low association for CC genotype, and moderate association for rs72559745 genotypes GG, AG. CONCLUSION: Conclusions: The mutant allele's genotypes of rs4149056, rs55901008, and rs72559745, and the wild allele genotype of rs2306283 show significant association with the development of poor response to atorvastatin and elevated the level of CK-MM plasma concentration.
Subject(s)
Dyslipidemias , Hydroxymethylglutaryl-CoA Reductase Inhibitors , Muscular Diseases , Organic Anion Transporters , Adult , Aged , Female , Humans , Male , Middle Aged , Atorvastatin/adverse effects , Cross-Sectional Studies , Dyslipidemias/drug therapy , Dyslipidemias/genetics , Genotype , Hydroxymethylglutaryl-CoA Reductase Inhibitors/adverse effects , Iraq , Liver-Specific Organic Anion Transporter 1/genetics , Muscular Diseases/chemically induced , Muscular Diseases/genetics , Muscular Diseases/epidemiology , Organic Anion Transporters/genetics , Polymorphism, GeneticABSTRACT
BACKGROUND: Insertion deletion (I/D) polymorphism (rs4646994) in the angiotensin-converting enzyme (ACE) has a substantial effect on coronary heart disease (CHD). The amplification of an Alu repetitive element in an intron of the ACE has shown three potential genotypes of I/I and D/D as homozygous, and I/D as heterozygous. OBJECTIVE: The objective of this study was to investigate the association between the ACE gene polymorphism and CHD among male Iraqi patients with and without type2 diabetes mellitus (T2DM). METHODS: A case-control study of total 217 male subjects participated in this study, divided into three groups; Group 1 including 86 CHD patients with T2DM, group 2 including 78 CHD patients without T2DM, and group 3 including 53 age and sex-matched healthy individuals (as a control group). Genotyping of ACE (I/D) gene was performed using polymerase chain reaction (PCR) technique. RESULTS: The II allele was significantly more frequent in CHD patients without T2DM compared to the control population, but not from those patients with T2DM (p < 0.05). Nonetheless, the ID allele was significantly more frequent in each of CHD with T2DM and control populations compared to the CHD without T2DM. The DD allele was significantly more frequent in CHD patients with T2DM compared to each of CHD patients without T2DM and control populations (p < 0.05). CONCLUSION: We conclude that the D/D and I/D genotypes are implicated as risk factors for development of CHD with T2DM, but not CHD without T2DM among the male Iraqi population. However, larger sample sizes are needed to monitor the CHD patients and to validate this study.
