Loci affecting gamma-glutamyl transferase in adults and adolescents show age x SNP interaction and cardiometabolic disease associations
Loci affecting gamma-glutamyl transferase in adults and adolescents show age x SNP interaction and cardiometabolic disease associations
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DOI：
10.1093/hmg/ddr478
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发表时间：
2012-01-15
影响因子：
3.5
通讯作者：
Whitfield, John B.
中科院分区：
文献类型：
--
作者：
Middelberg, Rita P.;Benyamin, Beben;Whitfield, John B.
血清γ -谷氨酰转移酶（GGT）活性是肝脏疾病的一个标志物，它也与全因死亡率、心血管疾病、2型糖尿病和癌症的风险有潜在的关联。我们在一项全基因组关联研究中发现了影响GGT的新位点(1号染色体基因间区rs1497406， P = 3.9 x 10(-8)；14号染色体C14orf73上的rs944002， P = 4.7 × 10(-13)；15号染色体RORA上的rs340005， P = 2.4 × 10(-8))， 22号染色体上的GGT1位点的成人和青少年结果具有高度显著的异质性(rs6519520上的最大P（HET) = 5.6 × 10(-12)）。对显著的和提示性的单核苷酸多态性关联的通路分析显示，影响GGT的基因与影响常见代谢性和炎症性疾病的基因之间存在显著的重叠，并确定了肝核因子（HNF）家族是影响GGT基因网络的控制者。我们的研究结果强化了GGT的疾病相关性，并证明GGT1位点的控制随年龄而变化。
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 x 10(-8); rs944002 in C14orf73 on chromosome 14, P = 4.7 x 10(-13); rs340005 in RORA on chromosome 15, P = 2.4 x 10(-8)), and a highly significant heterogeneity between adult and adolescent results at the GGT1 locus on chromosome 22 (maximum P(HET) = 5.6 x 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.