Genetic variation at NCAN locus is associated with inflammation and fibrosis in non-alcoholic fatty liver disease in morbid obesity.
Genetic variation at NCAN locus is associated with inflammation and fibrosis in non-alcoholic fatty liver disease in morbid obesity.
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DOI：
10.1159/000346195
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发表时间：
2013
期刊：
影响因子：
1.8
通讯作者：
GOLD Consortium
中科院分区：
文献类型：
--
作者：
Gorden A;Yang R;Yerges-Armstrong LM;Ryan KA;Speliotes E;Borecki IB;Harris TB;Chu X;Wood GC;Still CD;Shuldiner AR;Gerhard GS;GOLD Consortium
Obesity-associated non-alcoholic fatty liver disease (NAFLD) may cause liver dysfunction and failure. In a previously reported genome-wide association meta-analysis, single nucleotide polymorphisms (SNPs) near PNPLA3, NCAN, GCKR, LYPLAL1 and PPP1R3B were associated with NAFLD and with distinctive serum lipid profiles. The present study examined the relevance of these variants to NAFLD in extreme obesity. In 1,092 bariatric patients, the candidate SNPs were genotyped and association analyses with liver histology and serum lipids were performed. We replicated the association of hepatosteatosis with PNPLA3 rs738409[G] and with NCAN rs2228603[T]. We also replicated the association of rs2228603[T] with hepatic inflammation and fibrosis. Rs2228603[T] was associated with lower serum LDL, total cholesterol and triglycerides. After stratification by the presence or absence of NAFLD, these associations were present predominantly in the subgroup with NAFLD. NCAN rs2228603[T] is a risk factor for liver inflammation and fibrosis, suggesting that this locus is responsible for progression from steatosis to steatohepatitis. In this bariatric cohort, rs2228603[T] was associated with low serum lipids only in patients with NAFLD. This supports a NAFLD model in which the liver may sequester triglycerides as a result of either increased triglyceride uptake and/or decreased lipolysis.
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与人类血液低密度脂蛋白胆固醇、高密度脂蛋白胆固醇或甘油三酯相关的六个新位点。
影响因子：
30.8
作者：
Kathiresan, Sekar;Melander, Olle;Guiducci, Candace;Surti, Aarti;Burtt, Noel P.;Rieder, Mark J.;Cooper, Gregory M.;Roos, Charlotta;Voight, Benjamin F.;Havulinna, Aki S.;Wahlstrand, Bjorn;Hedner, Thomas;Corella, Dolores;Tai, E. Shyong;Ordovas, Jose M.;Berglund, Goran;Vartiainen, Erkki;Jousilahti, Pekka;Hedblad, Bo;Taskinen, Marja-Riitta;Newton-Cheh, Christopher;Salomaa, Veikko;Peltonen, Leena;Groop, Leif;Altshuler, David M.;Orho-Melander, Marju
通讯作者：
Orho-Melander, Marju
影响因子：
15.9
作者：
Nogueiras, Ruben;Wiedmer, Petra;Tschoep, Matthias H.
通讯作者：
Tschoep, Matthias H.
影响因子：
5.8
作者：
Pollin, Toni I.;Jablonski, Kathleen A.;Florez, Jose C.
通讯作者：
Florez, Jose C.
影响因子：
4.9
作者：
Romeo, S.;Sentinelli, F.;Baroni, M. G.
通讯作者：
Baroni, M. G.
影响因子：
13.5
作者：
Browning, JD;Szczepaniak, LS;Hobbs, HH
通讯作者：
Hobbs, HH