Pediatric non-alcoholic fatty liver disease and kidney function: Effect of HSD17B13 variant.
Pediatric non-alcoholic fatty liver disease and kidney function: Effect of HSD17B13 variant.
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儿童非酒精性脂肪肝和肾功能：HSD17B13变异的影响
DOI：
10.3748/wjg.v26.i36.5474
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发表时间：
2020-09-28
影响因子：
4.3
通讯作者：
Miraglia Del Giudice E
中科院分区：
文献类型：
--
作者：
Di Sessa A;Umano GR;Cirillo G;Passaro AP;Verde V;Cozzolino D;Guarino S;Marzuillo P;Miraglia Del Giudice E
越来越多的证据支持非酒精性脂肪肝 (NAFLD) 和慢性肾病 (CKD) 之间存在遗传联系。有趣的数据表明，主要的 NAFLD 风险多态性，例如含马铃薯蛋白样磷脂酶结构域 3 (PNPLA3) 中的 I148M 多态性和跨膜 6 超家族成员 2 基因 (TM6SF2) 中的 E167K 等位基因，都会影响肾功能。最近，羟基类固醇 17-β 脱氢酶 13 (HSD17B13) 基因被认为是参与 NAFLD 病理生理学的新型遗传变异。特别是，该基因的 rs72613567:TA 变体已被证明对成人和儿童的肝损伤具有保护作用。旨在研究 HSD17B13 基因的 rs72613567:TA 变体对肥胖儿童估计肾小球滤过率 (eGFR) 的影响。我们连续招募了 684 名肥胖儿童（平均年龄 10.56 ± 2.94 岁；平均 BMI-SDS 2.98 ± 0.78）到我们的肥胖诊所就诊。所有患者均接受了仔细的临床评估和全面的生化评估。为了检测肝脏脂肪变性，进行了肝脏超声检查。 NAFLD 的定义是超声检测到肝脏脂肪变性和/或丙氨酸转氨酶 (ALT) 水平 > 40 IU/L。研究人群根据 NAFLD 的存在情况进行划分。还对所有入组受试者的 HSD17B13 基因 rs72613567:TA 变体进行了基因分型。在患有和不患有 NAFLD 的受试者中，与纯合子患者相比，携带 HSD17B13 罕见 A 等位基因的患者表现出更高的 eGFR 水平。一般线性模型证实，无论是否患有 NAFLD 患者，eGFR 值与 HSD17B13 基因型均存在直接且显着的关联，与 PNPLA3 和 TM6SF2 多态性无关。回归线的比较证实了 HSD17B13 基因型对患有和不患有 NAFLD 患者的 eGFR 和年龄关系的影响。与携带 HSD17B13 罕见 A 等位基因的 NAFLD 患者相比，HSD17B13 基因型纯合子 NAFLD 患者的 eGFR 随着年龄的增长显着下降（截距 P 值 = 0.005；斜率 P 值 = 0.94）。在没有 NAFLD 的患者中也观察到了相同的效果（截距 P 值 = 0.0012；斜率 P 值 = 0.87）。在患有和不患有 NAFLD 的受试者中，HSD17B13 罕见 A 等位基因的携带者表现出比纯合受试者更高的 eGFR 水平，且与 PNPLA3 I148M 和 TM6SF6 E167K 多态性无关。
Growing evidence supports a genetic link between non-alcoholic fatty liver disease (NAFLD) and chronic kidney disease (CKD). Interesting data demonstrated that both the major NAFLD risk polymorphisms such as the I148M polymorphism in the patatin like phospholipase containing domain 3 (PNPLA3) and the E167K allele in the transmembrane 6 superfamily member 2 gene (TM6SF2) affect renal function. Recently the hydroxysteroid 17-beta dehydrogenase 13 (HSD17B13) gene has been recognized as a novel genetic variant involved in NAFLD pathophysiology. In particular, it has been showed the protective effect of the rs72613567:TA variant of this gene against liver damage both in adults and children. To investigate the impact of the rs72613567:TA variant of the HSD17B13 gene on estimated glomerular filtration rate (eGFR) in obese children. We enrolled 684 obese children (mean age 10.56 ± 2.94 years; mean BMI-SDS 2.98 ± 0.78) consecutively attending our Obesity Clinic. All the patients underwent a careful clinical assessment and a comprehensive biochemical evaluation. To detect hepatic steatosis, a liver ultrasound was performed. NAFLD was defined by ultrasound detected liver steatosis and/or alanine aminotransferase (ALT) levels > 40 IU/L. The study population was divided on the basis of the NAFLD presence. Genotyping for the rs72613567:TA variant of the HSD17B13 gene in all the enrolled subjects was also made. Patients carrying the HSD17B13 rare A allele showed higher eGFR levels compared with homozygous patients both among subjects with and without NAFLD. A general linear model confirmed a direct and significant association of eGFR values with HSD17B13 genotype independently of PNPLA3 and TM6SF2 polymorphisms both in patients with and without NAFLD. A comparison of regression line confirmed the influence of HSD17B13 genotype on the relationship between eGFR and age both among patients with and without NAFLD. Homozygous patients for HSD17B13 genotype with NAFLD showed a significantly higher decline of eGFR with the increase of the age compared with the patients with NAFLD carrying the HSD17B13 rare A allele (P value for intercepts = 0.005; P value for slopes = 0.94). The same effect was observed among patients without NAFLD (P value for intercepts = 0.0012; P value for slopes = 0.87). Carriers of the HSD17B13 rare A allele showed higher eGFR levels than homozygous subjects both among subjects with and without NAFLD and independently of PNPLA3 I148M and TM6SF6 E167K polymorphisms.
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影响因子：
3.2
作者：
Marzuillo, Pierluigi;Grandone, Anna;del Giudice, Emanuele Miraglia
通讯作者：
del Giudice, Emanuele Miraglia
影响因子：
3.8
作者：
Marzuillo, Pierluigi;Di Sessa, Anna;del Giudice, Emanuele Miraglia
通讯作者：
del Giudice, Emanuele Miraglia
DOI：
10.1097/mpg.0000000000001979
发表时间：
2018-07-01
影响因子：
2.9
作者：
Di Sessa, Anna;Umano, Giuseppina Rosaria;del Giudice, Emanuele Miraglia
通讯作者：
del Giudice, Emanuele Miraglia
影响因子：
6.7
作者：
Sun, Dan-Qin;Zheng, Kenneth, I;Zheng, Ming-Hua
通讯作者：
Zheng, Ming-Hua
影响因子：
3.6
作者：
Marzuillo, Pierluigi;Di Sessa, Anna;del Giudice, Emanuele Miraglia
通讯作者：
del Giudice, Emanuele Miraglia