Karla Mariana Alvarado-Retana, Daniel Francisco Ramos-Rosales, Elizabeth Irasema Antuna-Salcido, Sergio Manuel Salas-Pacheco, Francisco Xavier Castellanos-Juárez, Edna Madai Méndez-Hernández, Alma Cristina Salas-Leal, Osmel La Llave-León, Gerardo Quiñones-Canales, Oscar Arias-Carrión, Ada Sandoval-Carrillo, José Manuel Salas-Pacheco
{"title":"墨西哥人群中XPC rs2228001多态性与帕金森病风险的性别特异性关联:一项探索基因-环境相互作用的病例对照研究","authors":"Karla Mariana Alvarado-Retana, Daniel Francisco Ramos-Rosales, Elizabeth Irasema Antuna-Salcido, Sergio Manuel Salas-Pacheco, Francisco Xavier Castellanos-Juárez, Edna Madai Méndez-Hernández, Alma Cristina Salas-Leal, Osmel La Llave-León, Gerardo Quiñones-Canales, Oscar Arias-Carrión, Ada Sandoval-Carrillo, José Manuel Salas-Pacheco","doi":"10.3390/brainsci15091008","DOIUrl":null,"url":null,"abstract":"<p><strong>Background/objectives: </strong>Emerging evidence implicates impaired DNA repair mechanisms in the pathogenesis of Parkinson's disease (PD), particularly in the context of oxidative stress and environmental exposures. This study investigated the association between five polymorphisms in nucleotide excision repair (NER) pathway genes and PD susceptibility in a northern Mexican mestizo population.</p><p><strong>Methods: </strong>We conducted a case-control study including 137 patients with clinically diagnosed PD and 137 age- and sex-matched controls. Genomic DNA was isolated from peripheral blood, and genotyping of <i>ERCC1</i> (rs11615), <i>ERCC2</i> (rs13181), <i>XPA</i> (rs1800975), <i>XPC</i> (rs2228001), and <i>XPF</i> (rs1799801) was performed using TaqMan real-time PCR assays. Associations between genotype frequencies and PD were evaluated using logistic regression models adjusted for age, sex, and pesticide exposure.</p><p><strong>Results: </strong>A significantly higher prevalence of pesticide exposure was observed in PD patients than in controls (OR 2.08, 95% CI 1.18-3.68; <i>p</i> = 0.01). The <i>XPC</i> rs2228001 C/C genotype was independently associated with increased PD risk in males (OR 3.25, 95% CI 1.07-9.85; <i>p</i> = 0.042), even after adjusting for uric acid, pesticide exposure, and cognitive status (MMSE score). No significant associations were found for other NER-related polymorphisms. Male PD patients also exhibited significantly lower serum uric acid levels than controls (<i>p</i> = 0.046), supporting a link between oxidative stress and disease vulnerability.</p><p><strong>Conclusions: </strong>Our findings suggest a sex-specific genetic contribution to PD susceptibility involving the <i>XPC</i> rs2228001 variant, particularly in the context of pesticide exposure. These results underscore the relevance of DNA repair pathways in PD pathogenesis and highlight the importance of integrated models incorporating genetic and environmental risk factors.</p>","PeriodicalId":9095,"journal":{"name":"Brain Sciences","volume":"15 9","pages":""},"PeriodicalIF":2.8000,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12468217/pdf/","citationCount":"0","resultStr":"{\"title\":\"Sex-Specific Association Between XPC rs2228001 Polymorphism and Parkinson's Disease Risk in a Mexican Population: A Case-Control Study Exploring Gene-Environment Interactions.\",\"authors\":\"Karla Mariana Alvarado-Retana, Daniel Francisco Ramos-Rosales, Elizabeth Irasema Antuna-Salcido, Sergio Manuel Salas-Pacheco, Francisco Xavier Castellanos-Juárez, Edna Madai Méndez-Hernández, Alma Cristina Salas-Leal, Osmel La Llave-León, Gerardo Quiñones-Canales, Oscar Arias-Carrión, Ada Sandoval-Carrillo, José Manuel Salas-Pacheco\",\"doi\":\"10.3390/brainsci15091008\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background/objectives: </strong>Emerging evidence implicates impaired DNA repair mechanisms in the pathogenesis of Parkinson's disease (PD), particularly in the context of oxidative stress and environmental exposures. This study investigated the association between five polymorphisms in nucleotide excision repair (NER) pathway genes and PD susceptibility in a northern Mexican mestizo population.</p><p><strong>Methods: </strong>We conducted a case-control study including 137 patients with clinically diagnosed PD and 137 age- and sex-matched controls. Genomic DNA was isolated from peripheral blood, and genotyping of <i>ERCC1</i> (rs11615), <i>ERCC2</i> (rs13181), <i>XPA</i> (rs1800975), <i>XPC</i> (rs2228001), and <i>XPF</i> (rs1799801) was performed using TaqMan real-time PCR assays. Associations between genotype frequencies and PD were evaluated using logistic regression models adjusted for age, sex, and pesticide exposure.</p><p><strong>Results: </strong>A significantly higher prevalence of pesticide exposure was observed in PD patients than in controls (OR 2.08, 95% CI 1.18-3.68; <i>p</i> = 0.01). The <i>XPC</i> rs2228001 C/C genotype was independently associated with increased PD risk in males (OR 3.25, 95% CI 1.07-9.85; <i>p</i> = 0.042), even after adjusting for uric acid, pesticide exposure, and cognitive status (MMSE score). No significant associations were found for other NER-related polymorphisms. Male PD patients also exhibited significantly lower serum uric acid levels than controls (<i>p</i> = 0.046), supporting a link between oxidative stress and disease vulnerability.</p><p><strong>Conclusions: </strong>Our findings suggest a sex-specific genetic contribution to PD susceptibility involving the <i>XPC</i> rs2228001 variant, particularly in the context of pesticide exposure. 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引用次数: 0
摘要
背景/目的:新出现的证据表明,受损的DNA修复机制与帕金森病(PD)的发病机制有关,特别是在氧化应激和环境暴露的背景下。本研究调查了墨西哥北部混血儿人群中核苷酸切除修复(NER)通路基因的五种多态性与PD易感性之间的关系。方法:我们进行了一项病例对照研究,包括137名临床诊断为PD的患者和137名年龄和性别匹配的对照组。从外周血中分离基因组DNA,采用TaqMan实时PCR技术对ERCC1 (rs11615)、ERCC2 (rs13181)、XPA (rs1800975)、XPC (rs2228001)和XPF (rs1799801)进行基因分型。基因型频率与PD之间的关系通过调整年龄、性别和农药暴露的逻辑回归模型进行评估。结果:PD患者的农药暴露率明显高于对照组(OR 2.08, 95% CI 1.18-3.68; p = 0.01)。XPC rs2228001 C/C基因型与男性帕金森病风险增加独立相关(OR 3.25, 95% CI 1.07-9.85; p = 0.042),即使在调整了尿酸、农药暴露和认知状态(MMSE评分)后也是如此。其他与内质网相关的多态性未发现显著关联。男性PD患者的血清尿酸水平也明显低于对照组(p = 0.046),支持氧化应激与疾病易感性之间的联系。结论:我们的研究结果表明,涉及XPC rs2228001变异的PD易感性的性别特异性遗传贡献,特别是在农药暴露的背景下。这些结果强调了DNA修复途径在PD发病机制中的相关性,并强调了整合遗传和环境风险因素的综合模型的重要性。
Sex-Specific Association Between XPC rs2228001 Polymorphism and Parkinson's Disease Risk in a Mexican Population: A Case-Control Study Exploring Gene-Environment Interactions.
Background/objectives: Emerging evidence implicates impaired DNA repair mechanisms in the pathogenesis of Parkinson's disease (PD), particularly in the context of oxidative stress and environmental exposures. This study investigated the association between five polymorphisms in nucleotide excision repair (NER) pathway genes and PD susceptibility in a northern Mexican mestizo population.
Methods: We conducted a case-control study including 137 patients with clinically diagnosed PD and 137 age- and sex-matched controls. Genomic DNA was isolated from peripheral blood, and genotyping of ERCC1 (rs11615), ERCC2 (rs13181), XPA (rs1800975), XPC (rs2228001), and XPF (rs1799801) was performed using TaqMan real-time PCR assays. Associations between genotype frequencies and PD were evaluated using logistic regression models adjusted for age, sex, and pesticide exposure.
Results: A significantly higher prevalence of pesticide exposure was observed in PD patients than in controls (OR 2.08, 95% CI 1.18-3.68; p = 0.01). The XPC rs2228001 C/C genotype was independently associated with increased PD risk in males (OR 3.25, 95% CI 1.07-9.85; p = 0.042), even after adjusting for uric acid, pesticide exposure, and cognitive status (MMSE score). No significant associations were found for other NER-related polymorphisms. Male PD patients also exhibited significantly lower serum uric acid levels than controls (p = 0.046), supporting a link between oxidative stress and disease vulnerability.
Conclusions: Our findings suggest a sex-specific genetic contribution to PD susceptibility involving the XPC rs2228001 variant, particularly in the context of pesticide exposure. These results underscore the relevance of DNA repair pathways in PD pathogenesis and highlight the importance of integrated models incorporating genetic and environmental risk factors.
期刊介绍:
Brain Sciences (ISSN 2076-3425) is a peer-reviewed scientific journal that publishes original articles, critical reviews, research notes and short communications in the areas of cognitive neuroscience, developmental neuroscience, molecular and cellular neuroscience, neural engineering, neuroimaging, neurolinguistics, neuropathy, systems neuroscience, and theoretical and computational neuroscience. Our aim is to encourage scientists to publish their experimental and theoretical results in as much detail as possible. There is no restriction on the length of the papers. The full experimental details must be provided so that the results can be reproduced. Electronic files or software regarding the full details of the calculation and experimental procedure, if unable to be published in a normal way, can be deposited as supplementary material.