A common variant in the adiponutrin gene influences liver enzyme values.
A common variant in the adiponutrin gene influences liver enzyme values.
复制标题
脂肪酸蛋白酶基因的常见变体会影响肝酶值。
DOI：
10.1136/jmg.2009.066597
复制
发表时间：
2010-02
影响因子：
4
通讯作者：
Kronenberg F
中科院分区：
文献类型：
--
作者：
Kollerits B;Coassin S;Kiechl S;Hunt SC;Paulweber B;Willeit J;Brandstätter A;Lamina C;Adams TD;Kronenberg F
最近的两项全基因组关联研究发现，肝脏表达的跨膜蛋白脂联素与肝脏相关表型（例如非酒精性脂肪肝病和肝功能酶）相关。这些关联并没有针对不同种族进行统一报道。本研究的目的是调查 adiponutrin（rs738409，外显子 3）内常见的非同义变异以及三个独立的西欧亚研究人群（总共 4290 名参与者）的肝功能参数。该研究是在 1) 基于人群的 Bruneck 研究 (n=783)、2) 基于健康工作人群 (n=1705) 的奥地利 SAPHIR 研究以及犹他州肥胖病例对照研究中进行的，其中包括来自犹他州同一地理区域的 1019 名严重肥胖个体（平均 BMI 46.0 kg/m2）和 783 名对照。测量的肝酶为丙氨酸转氨酶（ALT）、天冬氨酸转氨酶（AST）和γ-谷氨酰转移酶（GGT）。我们发现这种多态性与年龄和性别调整的 ALT 和 AST 水平存在很强的隐性关联：次要等位基因纯合导致 ALT 水平显着增加 3.53 U/L (p=1.86×10−9)，AST 水平显着增加 2.07 U/L (p=9.58×10−6)。在所有三个研究人群中都一致发现了这种关联。总之，adiponutrin 基因内的这种颠换多态性与 ALT 和 AST 水平升高的高度显着关联支持 adiponutrin 作为肝功能障碍易感基因的作用。
Two recent genome-wide association studies identified the liver-expressed transmembrane protein adiponutrin to be associated with liver-related phenotypes such as nonalcoholic fatty liver disease and liver function enzymes. These associations were not uniformly reported for various ethnicities. The aim of this study was to investigate a common nonsynonymous variant within adiponutrin (rs738409, exon 3) with parameters of liver function in three independent West-Eurasian study populations including a total of 4290 participants. The study was performed in 1) the population-based Bruneck Study (n=783), 2) the SAPHIR Study from Austria based on a healthy working population (n=1705), and the Utah Obesity Case-Control Study including a group of 1019 severely obese individuals (average BMI 46.0 kg/m2) and 783 controls from the same geographical region of Utah. Liver enzymes measured were alanine-aminotransferase (ALT), aspartate-aminotransferase (AST) and gamma-glutamyl transferase (GGT). We found a strong recessive association of this polymorphism with age- and gender-adjusted ALT and AST levels: being homozygous for the minor allele resulted in a highly significant increase of ALT levels of 3.53 U/L (p=1.86×10−9) and of AST levels of 2.07 U/L (p=9.58×10−6), respectively. The associations were consistently found in all three study populations. In conclusion, the highly significant associations of this transversion polymorphism within the adiponutrin gene with increased ALT and AST levels support a role for adiponutrin as a susceptibility gene for hepatic dysfunction.
登录
查看更多内容
影响因子：
14.9
作者：
Ramensky, V;Bork, P;Sunyaev, S
通讯作者：
Sunyaev, S
影响因子：
6.5
作者：
Lake, AC;Sun, Y;Gimeno, RE
通讯作者：
Gimeno, RE
影响因子：
16.2
作者：
Brandstätter A;Kiechl S;Kollerits B;Hunt SC;Heid IM;Coassin S;Willeit J;Adams TD;Illig T;Hopkins PN;Kronenberg F
通讯作者：
Kronenberg F
影响因子：
6.9
作者：
Boes, Eva;Kollerits, Barbara;Kronenberg, Florian
通讯作者：
Kronenberg, Florian
影响因子：
5.8
作者：
Jimenez, Rafael C.;Quinn, Antony F.;Hermjakob, Henning
通讯作者：
Hermjakob, Henning