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

Abstract

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 (DβH) 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.

Keywords: Aging; Dementia; Dopamine beta-hydroxylase; Genetic; Polymorphism.