Interrogation of selected genes influencing serum LDL-Cholesterol levels in patients with well characterized NAFLD.
Interrogation of selected genes influencing serum LDL-Cholesterol levels in patients with well characterized NAFLD.
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DOI：
10.1016/j.jacl.2020.12.010
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发表时间：
2021-03
影响因子：
4.4
通讯作者：
Chalasani N
中科院分区：
文献类型：
--
作者：
Vilar-Gomez E;Gawrieh S;Liang T;McIntyre AD;Hegele RA;Chalasani N
The clinical significance of rare mutations in LDL metabolism genes on nonalcoholic fatty liver disease (NAFLD) severity is not well understood. To examine the significance of mutations in LDL metabolism genes including apolipoprotein B (APOB), proprotein convertase subtilisin kexin 9 (PCSK9) and LDL receptor (LDLR) in patients with NAFLD. Patients with biopsy-confirmed NAFLD from the NASH Clinical Research Network studies were stratified into 3 groups of LDL-C (≤ 50 mg/dL, 130–150 mg/dL, ≥ 190 mg/dL) and then 120 (40 per group) were randomly selected from the strata. We examined the presence of mutations on LDL genes and analyzed its association with selected NAFLD-related features. Multivariable analyses were adjusted for age, race, gender and use of statins. Among 40 patients with LDL-C ≤ 50 mg/dL, 7 (18%) patients had heterozygous variants in APOB and 2 had heterozygous variants in PCSK9 (5%). We also found heterozygous mutations in 3 (8%) patients with LDL-C ≥ 190 mg/dL; 2 and 1 located in LDLR and APOE genes, respectively. Compared to wild-type controls with LDL-C ≤ 50, APOB carriers displayed higher levels of alanine aminotransferase (85.86 ± 35.14 U/L vs 45.61 ± 20.84 U/L, Adj. P=0.002) and steatosis >66% (57% vs 24%, Adj. P=0.050). These associations remained statistically significant after excluding statin users. Other histological features of NAFLD severity were not different between wild-type controls and APOB mutation carriers. Mutations in the APOB gene are common among NAFLD patients with very low LDL-C and may be associated with increased aminotransferase levels and steatosis severity.
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DOI：
10.1002/hep.30350
发表时间：
2019-04
期刊：
Hepatology (Baltimore, Md.)
影响因子：
--
作者：
Ma Y;Belyaeva OV;Brown PM;Fujita K;Valles K;Karki S;de Boer YS;Koh C;Chen Y;Du X;Handelman SK;Chen V;Speliotes EK;Nestlerode C;Thomas E;Kleiner DE;Zmuda JM;Sanyal AJ;(for the Nonalcoholic Steatohepatitis Clinical Research Network);Kedishvili NY;Liang TJ;Rotman Y
通讯作者：
Rotman Y
影响因子：
4.8
作者：
Chen, ZJ;Fitzgerald, RL;Schonfeld, G
通讯作者：
Schonfeld, G
DOI：
10.1161/01.atv.19.11.2714
发表时间：
1999-11-01
影响因子：
8.7
作者：
Elias, N;Patterson, BW;Schonfeld, G
通讯作者：
Schonfeld, G
影响因子：
3.1
作者：
Lonardo, A;Tarugi, P;Bagni, A
通讯作者：
Bagni, A
影响因子：
5.3
作者：
Awan, Zuhier;Choi, Hong Y.;Genest, Jacques
通讯作者：
Genest, Jacques