Common genetic variation in vitamin D metabolism is associated with liver stiffness
Common genetic variation in vitamin D metabolism is associated with liver stiffness
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DOI：
10.1002/hep.25830
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发表时间：
2012-11-01
期刊：
影响因子：
13.5
通讯作者：
Lammert, Frank
中科院分区：
文献类型：
--
作者：
Gruenhage, Frank;Hochrath, Katrin;Lammert, Frank
最近，全基因组研究发现了影响健康人群血清 25-羟基维生素 D 水平的遗传变异（rs12785878，靠近脱氢胆固醇还原酶，DHCR7；rs10741657，位于 CYP2R1；rs7041，位于维生素 D 结合蛋白，GC）。由于维生素 D 缺乏与晚期肝病相关，因此我们假设这些变异与 25(OH)-维生素 D 水平和肝纤维化有关。总共包括 712 名患有慢性肝病的白人患者。通过瞬时弹性成像（TE）和/或组织学评估肝纤维化。 25(OH)-维生素 D 的血清水平与 TE 和纤维化阶段相关。使用 TaqMan 检测确定基因型，并测试其与维生素 D 和肝脏硬度的关联。血清 25(OH)-维生素 D 水平与肝脏硬度和组织学呈负相关 (P < 0.001)。罕见 DHCR7 等位基因或常见 CYP2R1 等位基因的纯合携带者 25(OH)-维生素 D 水平降低 (P < 0.05)。 DHCR7 位点中的变异 rs12785878 与两名 TE 患者的肝脏僵硬相关
Recently, genome-wide studies identified genetic variants that affect serum 25-hydroxyvitamin D levels in healthy populations (rs12785878, near dehydrocholesterol reductase, DHCR7; rs10741657, at CYP2R1; and rs7041, at vitamin D binding protein, GC). Because vitamin D deficiency is associated with advanced liver disease, we hypothesized that these variants are associated with 25(OH)-vitamin D levels and liver fibrosis. Overall, 712 Caucasian patients with chronic liver diseases were included. Liver fibrosis was assessed by transient elastography (TE) and/or histology. Serum levels of 25(OH)-vitamin D were correlated with TE and fibrosis stages. Genotypes were determined using TaqMan assays and tested for association with vitamin D and liver stiffness. Serum 25(OH)-vitamin D levels were inversely correlated with liver stiffness and histology (P < 0.001). Homozygous carriers of the rare DHCR7 allele or the common CYP2R1 allele presented with reduced 25(OH)-vitamin D levels (P < 0.05). The variant rs12785878 in the DHCR7 locus was associated with liver stiffness in both patients with TE