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.
J Clin Lab Anal. 2024 Jul;38(13-14):e25083. doi: 10.1002/jcla.25083. Epub 2024 Aug 6.
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.
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.
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).
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.
LIPA 位于 10q23.2-q23.3 染色体上，编码溶酶体酸性脂肪酶（LAL）（EC 3.1.1.13）。LIPA 的基因突变导致溶酶体酸性脂肪酶缺乏症（LALD），这是一种先天性错误，导致脂质代谢异常，损害胆固醇和三酰甘油的降解。已经记录了超过 40 种 LIPA 变体，但本研究仅关注其中两种。rs1051338 变体（NM_000235：c.46A>C）影响外显子 2 中的信号肽，而位于外显子 8 中的 rs116928232 改变剪接位点（NM_000235：c.894G>A），影响溶酶体酸性脂肪酶活性。鉴于 LALD 的临床表现多种多样，以及墨西哥人口中肝脂肪变性的患病率上升，主要是由于饮食原因，在这一人群中研究了这些变体，以发现潜在的致病因素。本研究旨在揭示西北墨西哥健康梅斯蒂索人 rs1051338 和 rs116928232 的频率，这是对该人群的一项重要遗传探索。
对 310 名健康梅斯蒂索人进行了这两种变体的 PCR-RFLP 分析，并对变体 rs116928232 进行了 Sanger 测序。还进行了生物信息学分析以预测蛋白质变化。
rs1051338（FA = 0.39，p 值 = 0.15）和 rs116928232（FA = 0.0016，p 值 = 0.49）的等位基因频率与报道的数据一致，而生物信息学分析允许我们识别两种变体中观察到的蛋白质变化；最后，变体之间没有连锁关系（归一化 D' = 1.03，p 值 = 0.56）。
等位基因频率与报道的数据非常吻合，蛋白质结构分析证实了变体对 LAL 酶功能的影响。值得注意的是，本研究首次对健康墨西哥梅斯蒂索人群中的 rs1051338 和 rs116928232 进行了分析。
