Wajsbrot Natalia Balassiano, Leite Nathalie Carvalho, Franca Paulo Henrique Condeixa, Cardoso Claudia Regina Lopes, Salles Gil Fernando, Villela-Nogueira Cristiane A
Division of Hepatology, Clementino Fraga Filho University Hospital, Federal University of Rio de Janeiro, Rua Professor Rodolpho Paulo Rocco, 255- Cidade Universitária, Rio de Janeiro, RJ, 20941-913, Brazil.
Post-Graduation Program On Health and Environment, University of the Region of Joinville (Univille), Santa Catarina, Brazil.
Dig Dis Sci. 2024 Feb;69(2):634-642. doi: 10.1007/s10620-023-08214-7. Epub 2023 Dec 19.
BACKGROUND & AIMS: In non-alcoholic fatty liver disease (NAFLD), the influence of parental history of type 2 diabetes (T2D) allied to single nucleotide polymorphisms (SNPs) in the offspring is not known. We aimed to investigate the impact of the parental history of T2D, PNPLA3 and TM6SF2 polymorphisms in liver steatosis and fibrosis.
This was a case-control study involving the offspring of T2D patients and controls without a parental history of T2D. Participants underwent clinical and laboratory evaluation, transient elastography (TE) by Fibroscan (Echosens, Fr) and genotyping for PNPLA3 and TM6SF2. Multivariate logistic regression evaluated the influence of parental history of T2D on liver steatosis and fibrosis, controlled for age, gender, metabolic traits and SNPs.
161 T2D offspring and 78 controls, 10-46 years old, were included. The offspring of T2D had higher prevalences of obesity, T2D, arterial hypertension and sedentarism. Parental history of T2D was associated with fibrosis ≥ F2 (OR 8.89, CI 95% 1.09-72.01, p = 0.041) after adjustment for age, gender, metabolic traits and SNPs. PNPLA3 GG genotype was independently associated with steatosis ≥ S1 (OR 8.15, CI 95% 1.93-34.38, p = 0.004) and fibrosis ≥ F2 (OR 4.31, CI 95% 1.11-16.61, p = 0.034).
The offspring of T2D patients present a worse metabolic profile and the parental history of T2D confers an increased likelihood of hepatic fibrosis, independent of metabolic factors. PNPLA3 homozygous GG, but not TM6SF2 genotypes, also impacts on this phenotype.
在非酒精性脂肪性肝病（NAFLD）中，2型糖尿病（T2D）家族史与单核苷酸多态性（SNP）对后代的影响尚不清楚。我们旨在研究T2D家族史、PNPLA3和TM6SF2基因多态性对肝脂肪变性和肝纤维化的影响。
这是一项病例对照研究，纳入了T2D患者的后代以及无T2D家族史的对照。参与者接受了临床和实验室评估、通过Fibroscan（Echosens，法国）进行的瞬时弹性成像（TE）以及PNPLA3和TM6SF2基因分型。多因素逻辑回归分析评估了T2D家族史对肝脂肪变性和肝纤维化的影响，并对年龄、性别、代谢特征和SNP进行了校正。
纳入了161名T2D患者的后代和78名对照，年龄在10至46岁之间。T2D患者的后代肥胖、T2D、动脉高血压和久坐不动的患病率更高。在校正年龄、性别、代谢特征和SNP后，T2D家族史与F2级及以上肝纤维化相关（比值比8.89，95%置信区间1.09 - 72.01，p =0.041）。PNPLA3基因的GG基因型与S1级及以上脂肪变性独立相关（比值比8.15，95%置信区间1.93 - 34.38，p =0.004）以及F2级及以上肝纤维化相关（比值比4.31，95%置信区间1.11 - 16.61，p = 0.034）。
T2D患者的后代具有更差的代谢特征，T2D家族史会增加肝纤维化的可能性，且独立于代谢因素。PNPLA3基因的纯合GG基因型而非TM6SF2基因型也会影响这一表型。
