NAFLD Research Center, Division of Gastroenterology, University of California at San Diego, La Jolla, California, USA.
Division of Gastroenterology, University of California at San Diego, La Jolla, California, USA.
Aliment Pharmacol Ther. 2023 May;57(10):1143-1150. doi: 10.1111/apt.17452. Epub 2023 Mar 16.
Adiposity amplifies the genetic risk of non-alcoholic fatty liver disease (NAFLD).
We evaluated the association between overweight-years, a cumulative exposure based on the product of the duration and severity of excess body weight (body mass index (BMI) ≥ 25 kg/m ), and genetic risk on liver fat and fibrosis.
This is a longitudinal analysis derived from a prospective cohort of adults in the Framingham Heart Study who underwent genotyping and vibration-controlled-transient-elastography with controlled attenuation parameter. Univariable and multivariable linear and logistic regression analyses were used to assess the association between overweight-years and liver fat and fibrosis. The association between genetic variants of liver fat (PNPLA3, TM6SF2, GCKR) and fibrosis (PNPLA3, TM6SF2, HSD17B13) was also assessed using a polygenic risk score.
Our sample included 2478 participants (54% women) with mean age and BMI of 40 (±8.5) years and 26.5(±5.1) kg/m , respectively. The mean follow-up was 14(±0.9) years, and each participant underwent three study visits. The prevalence of NAFLD was 28.3% (n = 700), and 207 (8.4%) had clinically significant fibrosis. In age-, sex- and diabetes-adjusted multivariable analyses, overweight-years (per SD) had a strong association with NAFLD (aOR 3.53 [95% CI: 3.10-4.02], p < 0.001), clinically significant fibrosis (aOR 1.60 [95% CI: 1.40-1.84], p < 0.001) and cirrhosis (aOR 1.81 [95% CI: 1.38-2.37], p < 0.001). High-polygenic risk was significantly associated with liver fat and clinically significant fibrosis (p < 0.05).
Overweight-years is strongly associated with NAFLD and clinically significant fibrosis and combined with polygenic risk may assist in defining the trajectory of NAFLD.
肥胖会放大非酒精性脂肪性肝病（NAFLD）的遗传风险。
我们评估了超重年数（基于超重持续时间和严重程度乘积的累积暴露，体重指数（BMI）≥25kg/m ）与遗传风险对肝脏脂肪和纤维化的关联。
这是一项来自弗雷明汉心脏研究前瞻性队列的纵向分析，该队列的成年人接受了基因分型和振动控制瞬态弹性成像，同时检测受控衰减参数。使用单变量和多变量线性和逻辑回归分析来评估超重年数与肝脏脂肪和纤维化之间的关系。还使用多基因风险评分评估了肝脏脂肪（PNPLA3、TM6SF2、GCKR）和纤维化（PNPLA3、TM6SF2、HSD17B13）遗传变异之间的关联。
我们的样本包括 2478 名参与者（54%为女性），平均年龄和 BMI 分别为 40（±8.5）岁和 26.5（±5.1）kg/m ，平均随访时间为 14（±0.9）年，每位参与者接受了三次研究访问。NAFLD 的患病率为 28.3%（n=700），207 例（8.4%）有临床显著纤维化。在年龄、性别和糖尿病调整后的多变量分析中，超重年数（每标准差）与 NAFLD 有很强的关联（OR 3.53 [95%CI：3.10-4.02]，p<0.001），与临床显著纤维化（OR 1.60 [95%CI：1.40-1.84]，p<0.001）和肝硬化（OR 1.81 [95%CI：1.38-2.37]，p<0.001）也有很强的关联。高多基因风险与肝脏脂肪和临床显著纤维化显著相关（p<0.05）。
超重年数与 NAFLD 和临床显著纤维化密切相关，与多基因风险相结合，可能有助于确定 NAFLD 的轨迹。
