Genome-wide association study identifies variants associated with histologic features of nonalcoholic Fatty liver disease.
Genome-wide association study identifies variants associated with histologic features of nonalcoholic Fatty liver disease.
复制标题
DOI：
10.1053/j.gastro.2010.07.057
复制
发表时间：
2010-11
期刊：
影响因子：
29.4
通讯作者：
Nonalcoholic Steatohepatitis Clinical Research Network
中科院分区：
文献类型：
--
作者：
Chalasani N;Guo X;Loomba R;Goodarzi MO;Haritunians T;Kwon S;Cui J;Taylor KD;Wilson L;Cummings OW;Chen YD;Rotter JI;Nonalcoholic Steatohepatitis Clinical Research Network
非酒精性脂肪性肝病（NAFLD）患者肝组织学的全基因组关联研究（GWAS）数据很少。我们在NASH CRN数据库研究中招募的NAFLD患者中进行了一项试点GWAS，其特征在于组织学。我们研究了236名非西班牙裔白人NAFLD女性的临床、实验室和组织学数据。我们分析了来自22条常染色体的324，623个单核苷酸多态性（SNP）。二元结果进行多变量调整逻辑回归分析，数量性状进行线性回归分析。P值< 1×10−6被认为是显著的。在校正了年龄、体重指数、糖尿病、腰臀比和血红蛋白A1c水平的多变量模型中，NAFLD活动评分与8号染色体上法尼基二磷酸法尼基转移酶1（FDFT 1）的SNP rs2645424相关（P=6.8×10−7）。纤维化程度与7号染色体上的SNP rs343062相关（P=2.7×10−8）。与小叶炎症相关的SNP包括COL13A1中10号染色体上的SNP rs1227756（P=2.0×10−7），11号染色体上的SNP rs6591182（P=8.6×10−7）和EFCAB4B中12号染色体上的SNP rs887304（P=7.7×10−7）。与血清丙氨酸转氨酶水平相关的SNP包括1号染色体上的rs2499604（P=2.2×10−6），PZP中12号染色体上的rs6487679（P=1.3×10−6），18号染色体上的rs1421201（P=1.0×10−5）和4号染色体上的rs2710833（P=6.3×10−7）。基因型与脂肪变性、气球样变性、门静脉炎症或NAFLD的其他特征之间没有显著相关性。在NAFLD患者中，GWAS将遗传变异与肝组织学特征显著相关。这些发现应该在更大和更多样化的队列中得到验证。
There is little data available from genome-wide association studies (GWAS) of liver histology in patients with non-alcoholic fatty liver disease (NAFLD). We conducted a pilot GWAS in patients with NAFLD, characterized by histology, who were enrolled in the NASH CRN Database Study. We studied clinical, laboratory, and histological data from 236 non-Hispanic Caucasian women with NAFLD. We analyzed 324,623 single nucleotide polymorphisms (SNPs) from the 22 autosomal chromosomes. Multivariate-adjusted logistic regression analyses were conducted for binary outcomes and linear regression analysis was applied for quantitative traits. A P-value < 1×10−6 was considered to be significant. In multivariate models adjusted for age, body mass index, diabetes, waist:hip ratios, and levels of hemoglobin A1c, the NAFLD activity score was associated with the SNP rs2645424 on chromosome 8 in farnesyl diphosphate farnesyl transferase 1 (FDFT1) (P=6.8×10−7). The degree of fibrosis was associated with the SNP rs343062 on chromosome 7 (P=2.7×10−8). SNPs associated with lobular inflammation included SNP rs1227756 on chromosome 10 in COL13A1 (P=2.0×10−7), rs6591182 on chromosome 11 (P=8.6×10−7), and rs887304 on chromosome 12 in EFCAB4B (P=7.7×10−7). SNPs associated with serum levels of alanine aminotransferase included rs2499604 on chromosome 1 (P=2.2×10−6), rs6487679 on chromosome 12 in PZP (P=1.3×10−6), rs1421201 on chromosome 18 (P=1.0×10−5), and rs2710833 on chromosome 4 (P=6.3×10−7). There were no significant associations between genotypes and steatosis, ballooning degeneration, portal inflammation, or other features of NAFLD. A GWAS significantly associated genetic variants with features of hepatic histology in patients with NAFLD. These findings should be validated in larger and more diverse cohorts.
登录
查看更多内容
影响因子：
30.8
作者：
Gunderson, KL;Steemers, FJ;Chee, MS
通讯作者：
Chee, MS
DOI：
10.1056/nejmoa072366
发表时间：
2007-08-02
期刊：
The New England journal of medicine
影响因子：
--
作者：
Samani NJ;Erdmann J;Hall AS;Hengstenberg C;Mangino M;Mayer B;Dixon RJ;Meitinger T;Braund P;Wichmann HE;Barrett JH;König IR;Stevens SE;Szymczak S;Tregouet DA;Iles MM;Pahlke F;Pollard H;Lieb W;Cambien F;Fischer M;Ouwehand W;Blankenberg S;Balmforth AJ;Baessler A;Ball SG;Strom TM;Braenne I;Gieger C;Deloukas P;Tobin MD;Ziegler A;Thompson JR;Schunkert H;WTCCC and the Cardiogenics Consortium
通讯作者：
WTCCC and the Cardiogenics Consortium
影响因子：
13.5
作者：
Browning, JD;Szczepaniak, LS;Hobbs, HH
通讯作者：
Hobbs, HH
影响因子：
3.9
作者：
NESS, GC;EALES, S;ZHAO, ZH
通讯作者：
ZHAO, ZH
影响因子：
13.5
作者：
Rotman, Yaron;Koh, Christopher;Zmuda, Joseph M.;Kleiner, David E.;Liang, T. Jake
通讯作者：
Liang, T. Jake