The association of genetic variability in patatin-like phospholipase domain-containing protein 3 (PNPLA3) with histological severity of nonalcoholic fatty liver disease.
The association of genetic variability in patatin-like phospholipase domain-containing protein 3 (PNPLA3) with histological severity of nonalcoholic fatty liver disease.
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DOI：
10.1002/hep.23759
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发表时间：
2010-09
期刊：
影响因子：
13.5
通讯作者：
Liang, T. Jake
中科院分区：
文献类型：
--
作者：
Rotman, Yaron;Koh, Christopher;Zmuda, Joseph M.;Kleiner, David E.;Liang, T. Jake
全基因组关联(GWA)研究发现了与肝脏脂肪增加或肝酶升高相关的单核苷酸多态(SNPs)，推测这可能反映了非酒精性脂肪性肝病(NAFLD)。在一大群NAFLD患者中，研究这些SNP是否与组织学严重程度相关。在GWA研究中，1117名(894名成人/223名儿童)在NASH-临床研究网络和美国国立卫生研究院临床中心的研究中登记了组织学证实的NAFLD的6个SNP的基因分型，这些SNP与肝脏脂肪或肝酶相关。在成人中，22号染色体上的3个SNPs与非酒精性脂肪性肝炎(NASH)的组织学参数相关。在调整了年龄、性别、糖尿病和饮酒后，编码I148M改变的PNPLA3(脂联素)基因中编码单核苷酸多态的非同义词rs738409C/G的次要等位基因与脂肪变性(p=0.03)、门脉炎症(p=2.5×10−4)、小叶炎(p=0.005)、马洛里-登克体(p=0.015)、非酒精性脂肪肝活动度评分(p=0.004)和纤维化(p=7.7×10−6)相关。SAMM50-PNPLA3簇中的另外两个SNP表现出类似的关联。Cpn1-ERLIN1-Chuk区域10号染色体上的3个SNP与肝纤维化独立相关(p=0.010)。在儿童中，没有SNP与组织学严重程度相关。然而，在多因素分析中，rs738409G等位基因与活检时的年龄相关(p=0.045)。在这个经组织学证实的NAFLD大型队列中，我们确认rs738409G等位基因与脂肪变性的关联，并描述其与组织学严重程度的关联。在儿科患者中，高危rs738409G等位基因与较早出现疾病相关。我们还描述了迄今未知的10号染色体SNPs与NASH纤维化严重程度之间的关联。
Genome wide association (GWA) studies identified single nucleotide polymorphisms (SNPs) that are associated with increased hepatic fat or elevated liver enzymes, presumably reflecting nonalcoholic fatty liver disease (NAFLD). To investigate whether these SNPs are associated with histological severity in a large cohort of NAFLD patients. 1117 (894 adults/223 children) individuals enrolled in NASH-Clinical Research Network and National Institutes of Health Clinical Center studies with histologically-confirmed NAFLD were genotyped for six SNPs that are associated with hepatic fat or liver enzymes in GWA studies. In adults, 3 SNPs on chromosome 22 showed associations with histological parameters of nonalcoholic steatohepatitis (NASH). After adjustment for age, gender, diabetes and alcohol consumption, the minor allele of rs738409C/G, a nonsynonymous coding SNP in the PNPLA3 (adiponutrin) gene encoding an I148M change, was associated with steatosis (p=0.03), portal inflammation (p=2.5×10−4), lobular inflammation (p=0.005), Mallory-Denk bodies (p=0.015), NAFLD activity score (NAS, p=0.004) and fibrosis (p=7.7×10−6). Two other SNPs in the SAMM50-PNPLA3 cluster demonstrated similar associations. Three SNPs on chromosome 10 in the CPN1-ERLIN1-CHUK region were independently associated with fibrosis (p=0.010). In children, no SNP was associated with histological severity. However, the rs738409 G allele was associated with younger age at the time of biopsy in multivariate analysis (p=0.045). In this large cohort of histologically-proven NAFLD, we confirm the association of the rs738409G allele with steatosis and describe its association with histological severity. In pediatric patients, the high-risk rs738409G allele is associated with an earlier presentation of disease. We also describe a hitherto unknown association between SNPs at a chromosome 10 locus and the severity of NASH fibrosis.
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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：
13.5
作者：
Browning, JD;Szczepaniak, LS;Hobbs, HH
通讯作者：
Hobbs, HH
影响因子：
13.5
作者：
Loomba, Rohit;Sirlin, Claude B.;Schwimmer, Jeffrey B.;Lavine, Joel E.
通讯作者：
Lavine, Joel E.
脂肪酸蛋白酶基因的常见变体会影响肝酶值。
影响因子：
4
作者：
Kollerits B;Coassin S;Kiechl S;Hunt SC;Paulweber B;Willeit J;Brandstätter A;Lamina C;Adams TD;Kronenberg F
通讯作者：
Kronenberg F
DOI：
10.1074/jbc.m109.064501
发表时间：
2010-02-26
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
He S;McPhaul C;Li JZ;Garuti R;Kinch L;Grishin NV;Cohen JC;Hobbs HH
通讯作者：
Hobbs HH