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Background/Objectives: MIR27A rs895819 polymorphism has emerged as a potential additional pharmacogenomic marker of fluoropyrimidine response. Current evidence on its potential effect on miR-27a expression, which represses DPD activity, leading to DPD deficiency and increased fluoropyrimidine-associated toxicity risk, is scarce and inconsistent. We have analyzed the effect of MIR27A rs895819 polymorphism on miR-27a-3p plasma expression levels under different models of inheritance to contribute further evidence on its plausible biological role in miR-27a expression. Methods: A total of 59 individuals with no medical history of cancer were included in this study. MIR27A rs895819 genotyping and miR-27a-3p expression were analyzed by using predesigned TaqMan assays. Results: The frequency of TT, TC, and CC genotypes was present at a prevalence of 50.8%, 44.1%, and 5.1%, respectively. Individuals carrying the CC genotype presented with decreased miR-27a-3p expression (0.422 fold-change versus TT, p = 0.041; 0.461 fold-change versus TC, p = 0.064), whereas no differences were present between TT and TC individuals (1.092 fold-change, p = 0.718). miR-27a-3p expression was decreased in CC individuals under a recessive model of inheritance (0.440 fold-change, p = 0.047). No differences were found in dominant (TT vs. TC+CC, 0.845 fold-change, p = 0.471) or over dominant (TT+CC vs. TC, 0.990 fold-change, p = 0.996) models of inheritance. Conclusions: MIR27A rs895819CC genotype leads to severely reduced miR-27a-3p expression in plasma. Further study of this association is warranted in cancer patients to apply MIR27A genotyping in therapeutics to identify fluoropyrimidine-treated patients who are at a decreased risk of experiencing fluoropyrimidine-induced severe toxicity. [ABSTRACT FROM AUTHOR]

Alcohol dependence is a serious psychiatric disorder with harmful physical, mental and social consequences, and a high probability of a chronic relapsing course. The field of pharmacologic treatment of alcohol dependence and craving is expanding rapidly; the drugs that have been found to reduce relapse rates or drinking in alcohol-dependent patients and are approved for treatment of alcohol dependence are naltrexone, acamprosate and disulfiram, whereas also topiramate appears as a promising therapy. For many patients, however, these treatments are not effective. Evidence from a number of different studies suggests that genetic variation is a significant contributor to interindividual variation of clinical presentation of alcohol problems and response to a given treatment. The aim of the present review is to summarize and discuss the findings on the association between gene polymorphisms and the response to alcohol dependence treatment medications. It is anticipated that future implementation of pharmacogenomics in clinical practice will help personalize alcohol dependence drug treatment, and development personalized hospital pharmacology.

Abstract Polymorphisms in the endothelial nitric oxide synthase (eNOS) gene (-786T >C and 894G >T) enhance endo-thelial dysfunction and have been studied in relation to coronary artery disease (CAD). In the present study, we examined the association of the above polymorphisms with CAD, as well as with myocardial infarction (MI), hypertension, diabetes and smoking in CAD patients. Study subjects consisted of 154 consecutive coronary artery bypass graft (CABG) patients and 155 non-CAD controls. eNOS -786T >C and 894G >T polymorphisms were genotyped by polymerase chain reaction-restriction fragment length polymorphism. The estimated frequencies of the -786C and 894T alleles did not differ between the two groups (p = 0.46 and p = 0.84, respectively). The prevalence of eNOS polymorphisms was not associated with MI, hypertension or diabetes in CABG patients; however, we found that the 894TT genotype and 894T allele were significantly more frequent in current/past smoker CABG patients (16.7 per cent and 39.6 per cent, respectively) compared with never smoker CABG patients (6.1 per cent and 24.4 per cent, respectively) (p = 0.01 and p < 0.01, respectively). We found no association of eNOS -786C and 894T variant alleles with CAD; however, within CABG patients, a gene-environment interaction was found between the eNOS 894T allele and smoking.

Hypoglycemia is the most common adverse effect of sulfonylureas (SUs) and a major concern when using these drugs. Transcription factor 7-like 2 (TCF7L2) rs7903146 C>T polymorphism is an established and well characterized genetic marker of type 2 diabetes (T2DM) risk. The aim of the present study was to analyze the potential association of TCF7L2 rs7903146 C>T polymorphism with SU-induced hypoglycemia in a well characterized cohort of SU-treated patients previously genotyped for cytochrome P450 2C9 (CYP2C9) and P450 oxidoreductase (POR). The study group consisted of 176 SU-treated T2DM patients of whom 92 had experienced at least one drug-associated hypoglycemic event. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was used for TCF7L2 rs7903146 genotyping. TCF7L2 rs7903146 C>T genotype and allele frequency did not differ between cases and controls (p=0.745 and 0.671, respectively). In logistic regression analysis adjusted for other factors affecting hypoglycemia, including CYP2C9 and POR genotypes, TCF7L2 rs7903146 C>T polymorphism did not increase the risk of hypoglycemia (OR=1.238, 95% C.I.=0.750–2.044, p=0.405). TCF7L2 rs7903146 C>T polymorphism is not associated with SU-induced hypoglycemia. Identifying additional gene polymorphisms associated with SU-induced hypoglycemia is crucial for improving T2DM patient therapy with SUs. [ABSTRACT FROM AUTHOR]