目的:本研究的目的是调查LYPLAL1、GCKR、HSD17B13、TRIB1、APOC3、MBOAT7和PARVB在小儿非酒精性脂肪性肝病中的作用,以及先前报道的TM6SF2、PNPLA3和SAMM50在韩国儿童中的变异。
方法:进行了一项前瞻性病例对照研究,涉及使用超声诊断的309例患者和339例对照。人体测量,肝功能检查,并进行了代谢标志物分析,计算纤维化评分。69例非酒精性脂肪性肝病患者进行了瞬时弹性成像。使用TaqMan等位基因鉴别测定进行基因分型。遗传风险评分是使用显著变异计算的,即,HSD17B13,PARVB,PNPLA3、SAMM50和TM6SF2,以评价其添加效应。
结果:PARVB变异体的风险等位基因携带者显示出明显更高水平的转氨酶,γ-谷氨酰转移酶,碱性磷酸酶,小儿非酒精性脂肪性肝病纤维化评分,天冬氨酸转氨酶/血小板比值指数。具有HSD17B13纯合变体的个体显示出明显较低水平的转氨酶,γ-谷氨酰转移酶,肝脏硬度测量,天门冬氨酸转氨酶/血小板比值指数高于其他基因型。这些参数在LYPLAL1,GCKR的其他变体中没有显着差异,TRIB1、APOC3和MBOAT7。遗传风险评分被确定为非酒精性脂肪性肝病的独立危险因素,并且与严重程度呈正相关。
结论:HSD17B13对小儿非酒精性脂肪性肝病的严重程度具有保护作用。HSD17B13、PARVB、PNPLA3、SAMM50和TM6SF2对非酒精性脂肪性肝病有累加效应。
OBJECTIVE: The aim of this study was to investigate the comprehensive genetic effects of exploratory variants of LYPLAL1, GCKR, HSD17B13, TRIB1, APOC3, MBOAT7, and PARVB on pediatric nonalcoholic fatty liver disease in addition to the previously reported variants of
TM6SF2, PNPLA3, and SAMM50 in Korean children.
METHODS: A prospective case-control study was conducted involving 309 patients diagnosed using ultrasound and 339 controls. Anthropometric measurements, liver function tests, and metabolic marker analysis were conducted, and fibrosis scores were calculated. Transient elastography was performed in 69 some patients with nonalcoholic fatty liver disease. TaqMan allelic discrimination assays were used for genotyping. The genetic risk scores were calculated using significant variants, namely, HSD17B13, PARVB, PNPLA3, SAMM50, and
TM6SF2, to evaluate the additive effect.
RESULTS: Risk allele carriers of the PARVB variant showed significantly higher levels of aminotransferases, gamma-glutamyl transferase, alkaline phosphatase, pediatric nonalcoholic fatty liver disease fibrosis score, and aspartate aminotransferase/platelet ratio index. Individuals with a homozygous variant of HSD17B13 showed significantly lower levels of aminotransferase, gamma-glutamyl transferase, liver stiffness measurement, and aspartate aminotransferase/platelet ratio index than those with other genotypes. These parameters did not significantly differ among other variants of LYPLAL1, GCKR, TRIB1, APOC3, and MBOAT7. The genetic risk scores was identified as an independent risk factor for nonalcoholic fatty liver disease and had a positive association with severity.
CONCLUSIONS: HSD17B13 has protective effects on the severity of pediatric nonalcoholic fatty liver disease. Variants of HSD17B13, PARVB, PNPLA3, SAMM50, and
TM6SF2 had an additive effect on nonalcoholic fatty liver disease.