Interactions of allelic variance of PNPLA3 with nongenetic factors in predicting nonalcoholic steatohepatitis and nonhepatic complications of severe obesity.
Interactions of allelic variance of PNPLA3 with nongenetic factors in predicting nonalcoholic steatohepatitis and nonhepatic complications of severe obesity.
复制标题
DOI：
10.1002/oby.20327
复制
发表时间：
2013-09
期刊：
影响因子：
6.9
通讯作者：
Charlton, M. R.
中科院分区：
文献类型：
--
作者：
Guichelaar, M. M. J.;Gawrieh, S.;Olivier, M.;Viker, K.;Krishnan, A.;Sanderson, S.;Malinchoc, M.;Watt, K. D.;Swain, J. M.;Sarr, M.;Charlton, M. R.
脂联素（patatin样磷脂酶结构域蛋白3，PNPLA 3）的等位基因变异（rs738409 C →G）与肝脂肪变性和肝纤维化相关。PNPLA 3 G等位基因的生理影响可能在重度肥胖患者中加剧。在这项研究中，我们研究了PNPLA 3 rs738409与医学复杂性肥胖患者的非酒精性脂肪性肝病和非酒精性脂肪性肝炎（NASH）的广泛代谢和组织学特征的相互作用。选择接受减肥手术的连续性患者进行前瞻性研究。他们进行了广泛的实验室和组织学（肝活检）评估，以及通过TaqMan分析评估rs738409多态性。144例患者中仅12例（8.3%）肝组织学正常，72例（50%）NASH，其中15例（占总患者的10.4%）为2-3期纤维化。PNPLA 3 GG基因型与血清丙氨酸氨基转移酶（ALT）、丙氨酸氨基转移酶（AST）、血糖、纤维蛋白原、胰岛素依赖型糖尿病、稳态模型评估胰岛素抵抗和NASH的存在正相关（P < 0.05）。多因素分析表明，PNPLA 3 rs738409 G与C等位基因仍然是NASH的（独立）危险因素，此外还有CK-18 >145 IU/l、葡萄糖>100 mg/dl和C反应蛋白（CRP）>0.8 mg/dl。NASH的概率从9%（无风险因素）增加到82%，如果所有四个风险因素都存在。在这组患有医学并发性肥胖症的患者中，PNPLA 3 rs738409 G等位基因表达与肥胖症的肝脏（NASH）和非肝脏并发症（如胰岛素抵抗）相关。这些新的发现可能与PNPLA 3变异体在严重肥胖患者中的影响程度和范围比在不太肥胖的人群中更大有关。需要进一步的研究来描述这些关联的性质。
Allelic variation (rs738409C→G) in adiponutrin (patatin-like phospholipase domain-containing protein 3, PNPLA3) has been associated with hepatic steatosis and liver fibrosis. The physiologic impact of the PNPLA3 G allele may be exacerbated in patients with severe obesity. In this study, we investigated the interactions of PNPLA3 rs738409 with a broad panel of metabolic and histologic characteristics of nonalcoholic fatty liver disease and nonalcoholic steatohepatitis (NASH) in patients with medically complicated obesity. Consecutive patients undergoing bariatric surgery were selected for a prospective study. They underwent extensive laboratory and histologic (liver biopsy) assessment, as well as evaluation of rs738409 polymorphism by TaqMan assay. Only 12 (8.3%) of the 144 patients had normal liver histology, with 72 (50%) NASH, of whom 15 (10.4% of total patients) had fibrosis stage 2–3. PNPLA3 GG genotype correlated positively (P < 0.05) with serum levels of alanine aminotransferase (ALT), asparate aminotransferase (AST), glucose, fibrinogen, and insulin-dependent diabetes mellitus, homeostasis model assessment—insulin resistance, and presence of NASH. Multivariate analysis indicated that PNPLA3 rs738409 G versus C allele remained an (independent) risk factor for NASH, in addition to CK-18 >145 IU/l, glucose >100 mg/dl, and C-reactive protein (CRP) >0.8 mg/dl. The probability of NASH increased from 9% (no risk factor) to 82% if all four risk factors were present. In this cohort of patients with medically complicated obesity, PNPLA3 rs738409 G allelic expression is associated with hepatic (NASH) and nonhepatic complications of obesity, such as insulin resistance. These novel findings may be related to a greater impact of PNPLA3 variant in magnitude and scope in patients with severe obesity than in less obese populations. Further studies are needed to characterize the nature of these associations.
登录
查看更多内容
携带 patatin 样磷脂酶 3 基因变体的人类脂肪肝与胰岛素抵抗之间的关联。
影响因子：
7.7
作者：
Kantartzis K;Peter A;Machicao F;Machann J;Wagner S;Königsrainer I;Königsrainer A;Schick F;Fritsche A;Häring HU;Stefan N
通讯作者：
Stefan N
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
影响因子：
6.5
作者：
Lake, AC;Sun, Y;Gimeno, RE
通讯作者：
Gimeno, RE
影响因子：
13.5
作者：
Sookoian, Silvia;Pirola, Carlos J.
通讯作者：
Pirola, Carlos J.