TY - CONF
T1 - Association of vitamin D serum levels and its common genetic determinants with severity of liver fibrosis in genotype 1 chronic hepatitis C patients
AU - Scazzone, Concetta
AU - Grimaudo, Stefania
AU - Craxi, Antonio
AU - Petta, Salvatore
AU - Camma', Calogero
AU - Pipitone, Rosaria Maria
AU - Di Marco, Vito
AU - Cabibi, Daniela
AU - Macaluso, Fabio Salvatore
PY - 2013
Y1 - 2013
N2 - Background and aims:Lower 25-Hydroxyvitamin D (25[OH]D) serum lev-els have been associated with the severity of liver fibrosis in genotype 1chronic hepatitis C patients (G1CHC). In addition, a recent genome-widestudy identified genetic variants (rs12785878, near dehydrocholesterol reduc-tase, DHCR7; rs10741657, near CYP2R1; and rs7041, near vitamin D bindingprotein, GC) affecting 25(OH)D serum levels in healthy populations. Weaimed to assess the association between vitamin D serum levels and its geneticdeterminants, with the severity of liver fibrosis.Material and methods:Two hundred sixty patients with biopsy-provenG1CHC were consecutively evaluated. The 25(OH)D serum levels were mea-sured by high-pressure liquid chromatography. All patients were genotyped forDHCR7 rs12785878, CYP2R1 rs10741657, and GC rs7041 single nucleotidepolymorphisms.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 inmultiple linear regression analysis. Interestingly, 53.8% (7/13) of patientswith DHCR7 GG genotype had severe liver fibrosis, compared to 27.1%(67/247) of those with DHCR7 TT/TG genotype (p=0.03), By multivariatelogistic regression analysis, severe fibrosis was independently associated witholder 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), andmoderate-severe necroinflammatory activity (grading) (OR, 2.437; 95% CI,1.307–4.763; p=0.001). No associations were found between liver fibrosis andboth CYP2R1 and GC genotypes.Conclusion:In G1CHC patients, GG homozygosis for DHCR7 gene andlower 25(OH)D levels are independently associated with the severity of liverfibrosis.
AB - Background and aims:Lower 25-Hydroxyvitamin D (25[OH]D) serum lev-els have been associated with the severity of liver fibrosis in genotype 1chronic hepatitis C patients (G1CHC). In addition, a recent genome-widestudy identified genetic variants (rs12785878, near dehydrocholesterol reduc-tase, DHCR7; rs10741657, near CYP2R1; and rs7041, near vitamin D bindingprotein, GC) affecting 25(OH)D serum levels in healthy populations. Weaimed to assess the association between vitamin D serum levels and its geneticdeterminants, with the severity of liver fibrosis.Material and methods:Two hundred sixty patients with biopsy-provenG1CHC were consecutively evaluated. The 25(OH)D serum levels were mea-sured by high-pressure liquid chromatography. All patients were genotyped forDHCR7 rs12785878, CYP2R1 rs10741657, and GC rs7041 single nucleotidepolymorphisms.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 inmultiple linear regression analysis. Interestingly, 53.8% (7/13) of patientswith DHCR7 GG genotype had severe liver fibrosis, compared to 27.1%(67/247) of those with DHCR7 TT/TG genotype (p=0.03), By multivariatelogistic regression analysis, severe fibrosis was independently associated witholder 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), andmoderate-severe necroinflammatory activity (grading) (OR, 2.437; 95% CI,1.307–4.763; p=0.001). No associations were found between liver fibrosis andboth CYP2R1 and GC genotypes.Conclusion:In G1CHC patients, GG homozygosis for DHCR7 gene andlower 25(OH)D levels are independently associated with the severity of liverfibrosis.
UR - http://hdl.handle.net/10447/119616
M3 - Other
ER -