Unidad de Investigación en Epidemiología y en Servicios de Salud Área Envejecimiento, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Av. Cuahutemoc 330. Col. Doctores. C.P.06720, Mexico City, Mexico.
Unidad de Investigación en Epidemiología Clínica, Hospital General Regional No 1 Carlos Mcgregor Sánchez Navarro, Gabriel Mancera 222 Esq. Xola, Col. Del Valle, Del. Benito Juárez, 03100, Ciudad de Mexico, Mexico.
Mol Neurobiol. 2023 Aug;60(8):4731-4737. doi: 10.1007/s12035-023-03367-y. Epub 2023 May 6.
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.
痴呆症是一种多因素疾病，其中环境、生活方式和遗传因素会起作用。人群研究已被用于寻找这种疾病的易感基因。由于脑中海马体和新皮质中的多巴胺 b 羟化酶（DβH）活性降低，因此报道了这种酶引起的阿尔茨海默病（AD）中多巴胺的生理状态发生变化。因此，DBH 多态性与 AD 等一些神经疾病的易感性有关，但很少有研究调查这些多态性与其他类型痴呆症之间的关系，特别是在墨西哥人群中。本研究旨在评估多巴胺 b-羟化酶（DBH 基因（rs1611115）单核苷酸多态性（SNP）与环境因素之间的关联及其与痴呆症风险的关系。我们检查了痴呆症患者和健康者的 DBH 基因（rs1611115）多态性基因型。通过多因素维度减少（MDR）分析检查了 DBH（rs1611115）多态性的相互作用及其对痴呆症的影响，结果通过卡方检验进行了验证。Hardy-Weinberg 平衡（HWE）也通过卡方检验进行了检查。相对风险用比值比（OR）和 95%表示。共有 221 名痴呆症患者和 534 名符合 MDR 分析纳入标准的对照者。MDR 分析结果表明，DBH1 基因座 rs1611115 TT 基因型与糖尿病、高血压和饮酒之间的相互作用与痴呆症的发生呈正相关（OR=6.5：95%CI=4.5-9.5），进而导致认知功能进一步受损。这些发现提供了一种认识，即通过 DBH rs1611115 多态性的隐性模型，代谢和心血管疾病与 T 等位基因之间存在正相关，这与痴呆症的易感性有关。
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