影响成年和青少年γ-谷氨酰转移酶的基因座表现出年龄×SNP 相互作用与心血管代谢疾病的关联。
Loci affecting gamma-glutamyl transferase in adults and adolescents show age × SNP interaction and cardiometabolic disease associations.
机构信息
Queensland Institute of Medical Research, Brisbane, Australia.
出版信息
Hum Mol Genet. 2012 Jan 15;21(2):446-55. doi: 10.1093/hmg/ddr478. Epub 2011 Oct 18.
Abstract
Serum gamma-glutamyl transferase (GGT) activity is a marker of liver disease which is also prospectively associated with the risk of all-cause mortality, cardiovascular disease, type 2 diabetes and cancers. We have discovered novel loci affecting GGT in a genome-wide association study (rs1497406 in an intergenic region of chromosome 1, P = 3.9 × 10(-8); rs944002 in C14orf73 on chromosome 14, P = 4.7 × 10(-13); rs340005 in RORA on chromosome 15, P = 2.4 × 10(-8)), and a highly significant heterogeneity between adult and adolescent results at the GGT1 locus on chromosome 22 (maximum P(HET) = 5.6 × 10(-12) at rs6519520). Pathway analysis of significant and suggestive single-nucleotide polymorphism associations showed significant overlap between genes affecting GGT and those affecting common metabolic and inflammatory diseases, and identified the hepatic nuclear factor (HNF) family as controllers of a network of genes affecting GGT. Our results reinforce the disease associations of GGT and demonstrate that control by the GGT1 locus varies with age.
摘要
血清γ-谷氨酰转移酶（GGT）活性是肝脏疾病的标志物，与全因死亡率、心血管疾病、2 型糖尿病和癌症的风险也具有前瞻性关联。我们在全基因组关联研究中发现了影响 GGT 的新基因座（位于 1 号染色体基因间区域的 rs1497406，P=3.9×10(-8)；位于 14 号染色体 C14orf73 上的 rs944002，P=4.7×10(-13)；位于 15 号染色体 RORA 上的 rs340005，P=2.4×10(-8)），并且在 22 号染色体 GGT1 基因座上，成年和青少年的结果之间存在非常显著的异质性（在 rs6519520 处最大 P(HET)=5.6×10(-12)）。对显著和提示性单核苷酸多态性关联的通路分析表明，影响 GGT 的基因与影响常见代谢和炎症性疾病的基因之间存在显著重叠，并确定了核因子（HNF）家族为影响 GGT 的基因网络的控制器。我们的研究结果加强了 GGT 的疾病相关性，并表明 GGT1 基因座的控制作用随年龄而变化。
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