Assessment of CFH and HTRA1 polymorphisms in age-related macular degeneration using classic and machine-learning approaches.

Autor: Martínez-Velasco A; Facultad De Ingeniería, Universidad Panamericana , Ciudad De México, Mexico., Perez-Ortiz AC; Universidad Panamericana. Facultad De Ciencias De La Salud. Ciudad De México, México.; Transplant Center, Division of Surgery, Massachusetts General Hospital , Boston, MA, USA., Antonio-Aguirre B; Universidad Panamericana. Facultad De Ciencias De La Salud. Ciudad De México, México., Martínez-Villaseñor L; Facultad De Ingeniería, Universidad Panamericana , Ciudad De México, Mexico., Lira-Romero E; Universidad Panamericana. Facultad De Ciencias De La Salud. Ciudad De México, México., Palacio-Pastrana C; Department of Microsurgery of the Anterior Segment, Fundación Hospital Nuestra Señora De La Luz, IAP , Ciudad De México, México.; Department of Microsurgery of the Anterior Segment, Clínicas Oftalmologicas Salauno Salud, Hamburgo, Ciudad de México, México., Zenteno JC; Department of Biochemistry, Faculty of Medicine, UNAM, Mexico City, Mexico., Ramirez I; Universidad Panamericana. Facultad De Ciencias De La Salud. Ciudad De México, México., Zepeda-Palacio C; Department of Microsurgery of the Anterior Segment, Fundación Hospital Nuestra Señora De La Luz, IAP , Ciudad De México, México., Mendoza-Velásquez C; Department of Microsurgery of the Anterior Segment, Fundación Hospital Nuestra Señora De La Luz, IAP , Ciudad De México, México., Camacho-Ordóñez A; Department of Microsurgery of the Anterior Segment, Fundación Hospital Nuestra Señora De La Luz, IAP , Ciudad De México, México., Ortiz Bibriesca DM; Facultad De Ingeniería, Universidad Panamericana , Ciudad De México, Mexico., Estrada-Mena FJ; Universidad Panamericana. Facultad De Ciencias De La Salud. Ciudad De México, México.
Jazyk: angličtina
Zdroj: Ophthalmic genetics [Ophthalmic Genet] 2020 Dec; Vol. 41 (6), pp. 539-547. Date of Electronic Publication: 2020 Aug 24.
DOI: 10.1080/13816810.2020.1804945
Abstrakt: Background: CFH and HTRA1 are pivotal genes driving increased risk for age-related macular degeneration (AMD) among several populations. Here, we performed a hospital-based case-control study to evaluate the effects of three single nucleotide polymorphisms (SNPs) among Hispanics from Mexico.
Materials and Methods: 122 cases and 249 controls were genotyped using Taqman probes. Experienced ophthalmologists diagnosed AMD following the American Association of Ophthalmology guidelines. We studied CFH (rs1329428, rs203687) and HTRA1 (rs11200638) SNPs thoroughly by logistic regression models (assuming different modes of inheritance) and machine learning-based methods (ML).
Results: HTRA1 rs11200638 is the most significant polymorphism associated with AMD in our studied population. In a multivariate regression model adjusted for clinically and statistically meaningful covariates, the A/G and A/A genotypes increased the odds of disease by a factor of 2.32 and 7.81, respectively ( P < .05) suggesting a multiplicative effect of the polymorphic A allele. Furthermore, this observation remains statistically meaningful in the allelic, dominant, and recessive models, and ML algorithms. When stratifying by phenotype, this polymorphism was significantly associated with increased odds for geographic atrophy (GA) in a recessive mode of inheritance (12.4, p < .05).
Conclusions: In sum, this work supports a strong association between HTRA1 genetic variants and AMD in Hispanics from Mexico, especially with GA. Moreover, ML was able to replicate the results of conventional biostatistics methods unbiasedly.
Databáze: MEDLINE
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