Association of vitamin D serum levels and its common genetic determinants with severity of liver fibrosis in genotype 1 chronic hepatitis C patients

Abstract

Background and aims: Lower 25-Hydroxyvitamin D (25[OH]D) serum lev- els 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 reduc- tase, 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. Material and methods: Two hundred sixty patients with biopsy-proven G1CHC were consecutively evaluated. The 25(OH)D serum levels were mea- sured by high-pressure liquid chromatography. All patients were genotyped for DHCR7 rs12785878, CYP2R1 rs10741657, and GC rs7041 single nucleotide polymorphisms. Results: 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. Conclusion: In G1CHC patients, GG homozygosis for DHCR7 gene and lower 25(OH)D levels are independently associated with the severity of liver fibrosis.