Multifactor Dimensionality Reduction Analysis to Evaluate the Association of Dopamine Beta-Hydroxylase (DΒH) Polymorphisms with Susceptibility to Dementia (SADEM Study).

Dementia is a multifactorial disease in which environmental, lifestyle, and genetic factors intervene. Population studies have been used in looking for the susceptibility genes for this disease. Since the activity of dopamine b hydroxylase (DßH) is reduced in the hippocampus and neocortex in the brain, changes in the physiological status of dopamine have been reported in Alzheimer's disease (AD) induced by this enzyme. Therefore, DBH polymorphisms have been associated with susceptibility to some neurological diseases such as AD, but few studies have investigated the relationship between these polymorphisms with other types of dementia, especially in Mexican populations. The aim of this study was to evaluate the association between single-nucleotide polymorphism (SNP) in the dopamine b-hydroxylase (DBH gene (rs1611115) and their interactions with environmental factors and the dementia risk. We examined the genotype of the gene DBH (rs1611115) polymorphism in patients with dementia and healthy. The interaction and the impact of DBH (rs1611115) polymorphism on dementia were examined through multifactor dimensionality reduction (MDR) analysis, and the results were verified by the Chi-square test. Hardy-Weinberg equilibrium (HWE) was also checked by the Chi-square test. The relative risk was expressed by odds ratio (OR) and 95%. A total of 221 dementia patients and 534 controls met the inclusion criteria of MDR analyses. The results of the MDR analysis showed that the development of dementia was positively correlated with interaction between the TT genotype of the DBH1 locus rs1611115 TT and diabetes, hypertension, and alcohol consumption (OR = 6.5: 95% CI = 4.5-9.5), originating further cognitive damage. These findings provide insight into the positive correlation between the metabolism and cardiovascular disorders and the presence of the T allele by means of a recessive model of DBH rs1611115 polymorphism with the suspensibility of dementia.

Clinical Weighting of Drug-Drug Interactions in Hospitalized Elderly.

Adverse drug reactions impact on patient health, effectiveness of pharmacological therapy and increased health care costs. This investigation intended to detect the most critical drug-drug interactions in hospitalized elderly patients, weighting clinical risk. We conducted a cross-sectional study between January and April 2014; all patients 70 years or older, hospitalized for >24 hr and prescribed at least one medication were included in the study. Drug-drug interactions were estimated by combining Stockley's, Hansten and Tatro drug interactions. Drug-drug interactions were weighted using a risk-analysis method based on failure modes, effects and criticality analysis. We calculated a criticality index for each drug involved in the drug-drug interactions based on the severity of the interaction mechanism, the frequency the drug was involved in drug-drug interactions and the risk of drug-drug interactions in patients with impaired renal function. The average number of drugs consumed in the hospital was 6 ± 2.69, involving 160 active ingredients. The most frequent were as follows: Furosemide, followed by Enalapril. Of drug-drug interactions, 2% were classified as contraindicated, 14% advised against and 83% advised caution during the hospital stay. Thirty-four drug-drug interactions were assessed, of which 23 were pharmacodynamic drug-drug interactions and 12 were pharmacokinetic drug-drug interactions (1 was both). The clinical risk calculated for each drug-drug interaction included heparins + non-steroidal anti-inflammatory drugs (NSAIDs) or Digoxin + Calcium Gluconate, cases which are pharmacodynamic drug-drug interactions with agonist effect and clinical risk of bleeding, one of the most common clinical risks in the hospital. An index of clinical risk for drug-drug interactions can be calculated based on severity by the interaction mechanism, the frequency that the drug is involved in drug-drug interactions and the risk of drug-drug interactions in an elderly patient with impaired renal function.