Rocha Sofia, Oliveira Claudia P, Stefano José Tadeu, Yokogawa Roberta P, Gomes-Gouvea Michele, Zitelli Patricia Momoyo Youshimura, Silva-Etto Joyce Matie Kinoshita, Martins Eduarda Donegá, Pessoa Mario G, Alcantara Flavio F, Azevedo Raymundo S, Rebello Pinho João Renato
Laboratório de Gastroenterologia e Hepatologia Tropical-LIM07, Faculdade de Medicina da Universidade de São Paulo (FMUSP), São Paulo 05508-000, SP, Brazil.
Laboratório de Gastroenterologia Clínica e Experimental-LIM07, Departamento de Gastroenterologia, Hospital das Clínicas Faculdade de Medicina da Universidade de São Paulo (HCFMUSP), São Paulo 05403-000, SP, Brazil.
Int J Mol Sci. 2025 Jul 3;26(13):6406. doi: 10.3390/ijms26136406.
Previous large-scale genetic studies identified single-nucleotide polymorphisms (SNPs) of the membrane bound O-acyltransferase domain containing 7 (MBOAT7) and patatin-like phospholipase domain containing 3 (PNPLA3) genes as risk factors for metabolic dysfunction-associated steatotic liver disease (MASLD). However, this has not yet been investigated in Brazilian patients. In this study, we evaluated the association between the PNPLA3 variant rs738409 and MBOAT7 variant rs641738 and the risk of hepatic fibrosis or liver cirrhosis in MASLD etiology. In parallel, we also aimed to evaluate a protective SNP of the mitochondrial amidoxime-reducing component 1 (MTARC1) gene. We also evaluated TM6SF2 rs58542926, GCKR rs1260326 and rs780094, and HSD17B13 rs72613567 and they were not associated with liver fibrosis. The study was conducted at the Department of Gastroenterology and Nutrology, Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (HCFMUSP), and included 113 patients with liver fibrosis (F0-F1), 99 patients with significant liver fibrosis (F2-F4), and 90 controls. SNPs were genotyped by quantitative PCR, using TaqMan allelic discrimination assays. Overall, the PNPLA3 GG genotype was more frequent in F2-F4 (23%) and F0-F1 (22%) patients than in controls (9%; = 0.02). The MBOAT7 TT genotype was significantly associated with fibrosis, with a prevalence of 23% in F2-F4 patients versus 10% in F0-F1 and 11% in controls ( = 0.01). This association was confirmed by regression analysis (OR = 5.01 95% CI: 1.86-13.49; = 1.41 × 10). The protective MTARC1 AA genotypes were more frequent in controls (52%) when compared to patients with fibrosis (5% = 2.76 × 10).
先前的大规模基因研究确定，含膜结合O-酰基转移酶结构域7（MBOAT7）和含帕他汀样磷脂酶结构域3（PNPLA3）基因的单核苷酸多态性（SNP）是代谢功能障碍相关脂肪性肝病（MASLD）的危险因素。然而，尚未在巴西患者中对此进行研究。在本研究中，我们评估了PNPLA3基因变体rs738409和MBOAT7基因变体rs641738与MASLD病因中肝纤维化或肝硬化风险之间的关联。同时，我们还旨在评估线粒体偕胺肟还原成分1（MTARC1）基因的一个保护性SNP。我们还评估了TM6SF2 rs58542926、GCKR rs1260326和rs780094，以及HSD17B13 rs72613567，它们与肝纤维化无关。该研究在圣保罗大学医学院临床医院胃肠病学和营养学系进行，纳入了113例肝纤维化（F0-F1）患者、99例显著肝纤维化（F2-F4）患者和90例对照。使用TaqMan等位基因鉴别分析通过定量PCR对SNP进行基因分型。总体而言，PNPLA3基因GG基因型在F2-F4患者（23%）和F0-F1患者（22%）中比在对照中（9%；P = 0.02）更常见。MBOAT7基因TT基因型与纤维化显著相关，在F2-F4患者中的患病率为23%，而在F0-F1患者中为10%，在对照中为11%（P = 0.01）。回归分析证实了这种关联（OR = 5.01，95%CI：1.86-13.49；P = 1.41×10）。与纤维化患者（5%，P = 2.76×10）相比，保护性MTARC1基因AA基因型在对照中（52%）更常见。
