Jain Shubham, Thanage Ravi, Panchal Falguni, Rathi Pravin M, Munshi Renuka, Udgirkar Suhas S, Contractor Qais Q, Chandnani Sanjay J, Sujit Nair P, Debnath Partha, Singh Anupam
Department of Gastroenterology, Topiwala National Medical College and BYL Ch Hospital, Dr. A.L Nair Road, Mumbai, Maharashtra, 400 008, India.
Molecular Genetic Laboratory, Department of Clinical Pharmacology, Topiwala National Medical College and BYL Nair Ch.Hospital, Dr.AL Nair Road, Mumbai, Maharashtra, 400 008, India.
J Clin Exp Hepatol. 2021 Jul-Aug;11(4):466-474. doi: 10.1016/j.jceh.2020.10.003. Epub 2020 Oct 10.
BACKGROUND & AIMS: Nonalcoholic fatty liver disease (NAFLD) has multifactorial origin. Genetic and environmental factors lead to the biology of this complex disorder. In this study, we screened parents of cases with NAFLD and compared them with parents of cases without NAFLD to see its familial aggregation and the role of patatin-like phospholipase domain containing 3 (PNPLA3).
It was a cross-sectional study. Parents of probands with NAFLD and without NAFLD were screened with abdominal sonography, anthropometry, blood tests, transient elastography, and PNPLA3 polymorphism.
We had enrolled 303 individuals: 51 probands with NAFLD, 50 probands without NAFLD, and their 202 parents. Parents of the NAFLD group had significantly higher metabolic risk factors as compared with parents of the non-NAFLD group. They had a significantly higher rate of fatty liver ( = 0.0001), mean serum aspartate aminotransferase levels ( = 0.011), mean serum alanine aminotransferase levels ( = 0.001),raised fasting and postprandial blood sugar levels, lower mean platelets (P = 0.033) and serum albumin levels ( = 0.005), and higher mean liver stiffness ( = 0.001) on transient elastography.Frequency of PNPLA3 polymorphism within NAFLD group was higher compared to the non-NAFLD group (mutant GG-13.3 vs 3.3%). Similarly, parents of NAFLD group had mutant GG in 15 % versus 5% in parents of non-NAFLD group, ( = 0.105, odds ratio 6), though it was not statistically significant but may be relevant. In this study, offsprings of parents with nonalcoholic steatohepatitis were likely to have GG homozygous allele. A NAFLD16 score based on parent's parameters was calculated to predict the probability of NAFLD occurrence in an overweight obese individual.
Screening of parents of individuals with NAFLD will help in the identification of undiagnosed NAFLD cases and other metabolic risk factors among them as there is a familial aggregation of NAFLD. One can predict the occurrence of NAFLD in the next generation using the NAFLD16 score.
非酒精性脂肪性肝病（NAFLD）病因多因素。遗传和环境因素导致了这种复杂疾病的生物学特性。在本研究中，我们对NAFLD病例的父母进行筛查，并与无NAFLD病例的父母进行比较，以观察其家族聚集性以及含patatin样磷脂酶结构域3（PNPLA3）的作用。
这是一项横断面研究。对患有NAFLD和未患有NAFLD的先证者的父母进行腹部超声、人体测量、血液检查、瞬时弹性成像和PNPLA3基因多态性筛查。
我们纳入了303名个体：51名患有NAFLD的先证者、50名未患有NAFLD的先证者以及他们的202名父母。与非NAFLD组的父母相比，NAFLD组的父母有显著更高的代谢危险因素。他们有显著更高的脂肪肝发生率（P = 0.0001）、平均血清天冬氨酸氨基转移酶水平（P = 0.011）、平均血清丙氨酸氨基转移酶水平（P = 0.001）、空腹和餐后血糖水平升高、平均血小板较低（P = 0.033）和血清白蛋白水平较低（P = 0.005），以及在瞬时弹性成像上有更高的平均肝脏硬度（P = 0.001）。NAFLD组中PNPLA3基因多态性的频率高于非NAFLD组（突变型GG - 13.3%对3.3%）。同样，NAFLD组的父母中有15%携带突变型GG，而非NAFLD组的父母中为5%，（P = 0.105，优势比6），虽然无统计学意义但可能相关。在本研究中，患有非酒精性脂肪性肝炎的父母的后代更可能有GG纯合等位基因。基于父母参数计算出NAFLD16评分，以预测超重肥胖个体发生NAFLD的概率。
对NAFLD个体的父母进行筛查将有助于识别未诊断的NAFLD病例及其它代谢危险因素，因为存在NAFLD的家族聚集性。使用NAFLD16评分可以预测下一代NAFLD的发生。
