Cattedra di Gastroenterologia, DiBiMIS, University of Palermo, Palermo, Italy.
J Viral Hepat. 2013 Jul;20(7):486-93. doi: 10.1111/jvh.12072. Epub 2013 Mar 25.
Lower 25-hydroxyvitamin D [25(OH)D] serum levels have been associated with the severity of liver fibrosis in genotype 1 chronic hepatitis C patients (G1CHC). In addition, a recent genome-wide study identified genetic variants (rs12785878, near dehydrocholesterol reductase, DHCR7; rs10741657, near CYP2R1; and rs7041, near vitamin D-binding protein, GC) affecting 25(OH)D serum levels in healthy populations. We aimed to assess the association between vitamin D serum levels and its genetic determinants, with the severity of liver fibrosis. Two hundred and sixty patients with biopsy-proven G1CHC were consecutively evaluated. The 25(OH)D serum levels were measured by high-pressure liquid chromatography. All patients were genotyped for DHCR7 rs12785878, CYP2R1 rs10741657 and GC rs7041 single nucleotide polymorphisms. DHCR7 GG genotype (P = 0.003) and the severity of fibrosis (P = 0.03) were independent factors associated with lower 25(OH)D serum levels in multiple linear regression analysis. Interestingly, 53.8% (7/13) of patients with DHCR7 GG genotype had severe liver fibrosis, compared to 27.1% (67/247) of those with DHCR7 TT/TG genotype (P = 0.03). By multivariate logistic regression analysis, severe fibrosis was independently associated with older age (OR, 1.056; 95% CI, 1.023-1.089, P = 0.001), low cholesterol (OR, 0.984; 95% CI, 0.974-0.994, P = 0.002), high triglycerides (OR, 1.008; 95% CI, 1.002-1.015, P = 0.01), low 25(OH)D (OR, 0.958; 95% CI, 0.919-0.999, P = 0.04), DHCR7 GG genotype (OR, 4.222; 95% CI, 1.106-16.120; P = 0.03), moderate-severe steatosis (OR, 2.588; 95% CI, 1.355-4.943; P = 0.004) and moderate-severe necroinflammatory activity (grading) (OR, 2.437; 95% CI, 1.307-4.763; P = 0.001). No associations were found between liver fibrosis and both CYP2R1 and GC genotypes. In patients with G1CHC, GG homozygosis for DHCR7 gene and lower 25(OH)D levels are independently associated with the severity of liver fibrosis.
25-羟维生素 D [25(OH)D] 血清水平较低与基因型 1 慢性丙型肝炎患者 (G1CHC) 的肝纤维化严重程度有关。此外，最近的全基因组研究确定了影响健康人群 25(OH)D 血清水平的遗传变异 (rs12785878，位于脱氢胆固醇还原酶 DHCR7 附近;rs10741657，位于 CYP2R1 附近;和 rs7041，位于维生素 D 结合蛋白 GC 附近)。我们旨在评估维生素 D 血清水平及其遗传决定因素与肝纤维化严重程度之间的关系。连续评估了 260 名经活检证实的 G1CHC 患者。采用高效液相色谱法测定 25(OH)D 血清水平。对所有患者进行 DHCR7 rs12785878、CYP2R1 rs10741657 和 GC rs7041 单核苷酸多态性的基因分型。多线性回归分析显示，DHCR7 GG 基因型 (P = 0.003) 和纤维化严重程度 (P = 0.03) 是与 25(OH)D 血清水平降低相关的独立因素。有趣的是，53.8% (7/13) 的 DHCR7 GG 基因型患者存在严重肝纤维化，而 DHCR7 TT/TG 基因型患者为 27.1% (67/247) (P = 0.03)。通过多变量逻辑回归分析，严重纤维化与年龄较大 (OR，1.056;95%CI，1.023-1.089，P = 0.001)、胆固醇水平较低 (OR，0.984;95%CI，0.974-0.994，P = 0.002)、甘油三酯水平较高 (OR，1.008;95%CI，1.002-1.015，P = 0.01)、25(OH)D 水平较低 (OR，0.958;95%CI，0.919-0.999，P = 0.04)、DHCR7 GG 基因型 (OR，4.222;95%CI，1.106-16.120;P = 0.03)、中重度脂肪变性 (OR，2.588;95%CI，1.355-4.943;P = 0.004) 和中重度坏死性炎症活动 (分级) (OR，2.437;95%CI，1.307-4.763;P = 0.001)。在 G1CHC 患者中，DHCR7 基因的 GG 纯合子和较低的 25(OH)D 水平与肝纤维化的严重程度独立相关。
