Frequency of rs1051338 and rs116928232 Variants in Individuals from Northwest Mexico.

Autor: Hernández-Orozco AA; Doctorado en Genética Humana, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara, Mexico.; Laboratorio de Diagnóstico Bioquímico de Enfermedades Lisosomales, División de Genética, Centro de Investigación Biomédica de Occidente (CIBO), Instituto Mexicano del Seguro Social (IMSS), Guadalajara Jalisco, Mexico., Melendez-Aranda L; Estancia Postdoctoral académica CONACYT, Centro de investigación en dinámica Molecular, Universidad Autónoma del Estado de Morelos (UAEM), Cuernavaca, Mexico., Mendoza-Ruvalcaba SDC; Laboratorio de Diagnóstico Bioquímico de Enfermedades Lisosomales, División de Genética, Centro de Investigación Biomédica de Occidente (CIBO), Instituto Mexicano del Seguro Social (IMSS), Guadalajara Jalisco, Mexico., Perea-Díaz FJ; Laboratorio de Genética 2, División de Genética, Centro de Investigación Biomédica de Occidente (CIBO), Instituto Mexicano del Seguro Social (IMSS), Guadalajara Jalisco, Mexico., Cebolla JJ; Departamento de Bioquímica, Biología Molecular y Celular, Facultad de Ciencias, Universidad de Zaragoza, Zaragoza, Spain., Giraldo P; Fundación Española Estudio y Terapéutica Enfermedad de Gaucher y Otras Lisosomales (FEETEG), Zaragoza, Spain., Brambila-Tapia AJL; Departamento de Psicología Básica, Centro Universitario de Ciencias de la Salud (CUCS), Universidad de Guadalajara, Guadalajara, Jalisco, Mexico., García-Ortíz JE; División de Genética, Centro de Investigación Biomédica de Occidente (CIBO), Instituto Mexicano del Seguro Social (IMSS), Guadalajara Jalisco, Mexico.
Jazyk: angličtina
Zdroj: Journal of clinical laboratory analysis [J Clin Lab Anal] 2024 Jul; Vol. 38 (13-14), pp. e25083. Date of Electronic Publication: 2024 Aug 06.
DOI: 10.1002/jcla.25083
Abstrakt: Background: LIPA, situated on chromosome 10q23.2-q23.3, encodes the enzyme lysosomal acid lipase (LAL) (EC 3.1.1.13). Genetic alterations in LIPA lead to lysosomal acid lipase deficiency (LALD), an inborn error causing lipid metabolism anomalies and impairing cholesterol and triacylglyceride degradation. Over 40 LIPA variants have been documented, yet this study focuses on just two. The rs1051338 variant (NM_000235:c.46A>C) affects the signal peptide in Exon 2, whereas rs116928232, located in Exon 8, alters the splice site (NM_000235:c.894G>A), impacting lysosomal acid lipase activity. Considering the diverse clinical manifestations of LALD and the rising hepatic steatosis prevalence in Mexican population, mainly due to diet, these variants were investigated within this demographic to uncover potential contributing factors. This study aimed to reveal the frequency of rs1051338 and rs116928232 among healthy mestizo individuals in Northwest Mexico, marking a significant genetic exploration in this demographic.
Methods: Three hundred ten healthy mestizo individuals underwent PCR-RFLP analysis for both variants, and Sanger sequencing was performed for variant rs116928232. Bioinformatic analysis was also performed to predict protein changes.
Results: Allele frequencies for rs1051338 (FA = 0.39, p value = 0.15) and rs116928232 (FA = 0.0016, p value = 0.49) aligned with reported data, while bioinformatic analysis allowed us to identify the protein alteration observed in both variants; finally, the variants showed no linkage between them (normalized D' = 1.03, p value = 0.56).
Conclusions: Allelic frequencies closely matched reported data, and protein structure analysis confirmed variant impacts on LAL enzyme function. Notably, this study marks the first analysis of rs1051338 and rs116928232 in a healthy Mexican mestizo population.
(© 2024 The Author(s). Journal of Clinical Laboratory Analysis published by Wiley Periodicals LLC.)
Databáze: MEDLINE
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