440 KLF12 POLYMORPHISM rs9543524 PREDICTS ANEMIA IN PATIENTS WITH CHRONIC HEPATITIS C TREATED WITH PEGINTERFERON AND RIBAVIRIN

Ampuero, Javier; Paz, Ido; Ferrero, Paula Gallego; Rojas, Liliana; Ortíz-Fernández, Lourdes; García-Lozano, José R.; Solà, R.; Forns, Xavier; Millán, Raquel; Escribano, M. González; Romero-Gómez, María Pilar

doi:10.1016/s0168-8278(13)60442-0

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“…KLF12 belongs to the Kruppel‐like zinc finger protein family and functions as transcription factor . A study by Ampuero et al showed that the KLF12 ‐TT genotype was associated with therapy‐related anemia in 565 Spanish CHC patients under a peg‐IFN/RBV regimen, raising the possibility that the KLF12 SNP is associated with adverse effects of IFN/RBV treatment. Our results support such a link.…”

Section: Discussionmentioning

confidence: 99%

“…The SLC29A1 rs760370 polymorphism results in higher RBV plasma concentrations, leading to a rapid viral response and RBV‐induced anemia in CHC patients . The rs9543524 SNP is located on the Kruppel‐like factor 12 (KLF12) gene and was reported to be a predictor for RBV‐induced anemia in 565 Spanish CHC patients treated with peg‐IFN/RBV . However, the association of these SNPs with spontaneous viral clearance and responses to peg‐IFN/RBV therapy in Chinese CHC patients has not been assessed.…”

Section: Introductionmentioning

confidence: 99%

“…[20][21][22][23] The rs9543524 SNP is located on the Kruppel-like factor 12 (KLF12) gene and was reported to be a predictor for RBV-induced anemia in 565 Spanish CHC patients treated with peg-IFN/RBV. 24 However, the association of these SNPs with spontaneous viral clearance and responses to peg-IFN/RBV therapy in Chinese CHC patients has not been assessed.…”

Section: Introductionmentioning

confidence: 99%

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Sustained viral response and treatment‐induced cytopenia correlate with SLCs and KLF12 genotypes in interferon/ribavirin‐treated Chinese chronic hepatitis C patients

Mei

Chi

et al. 2016

J of Gastro and Hepatol

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Background and aim: Genetic variations in solute carrier (SLC) genes are associated with liver diseases, and Kruppel-like factor 12 (KLF12) affects the b chain of hemoglobin. We investigated possible correlations of SLC and KLF12 polymorphisms with viral clearance (spontaneous and treatment-induced) and adverse effects in Chinese chronic hepatitis C (CHC) patients. Methods: We genotyped the single nucleotide polymorphisms in 525 CHC patients, 137 patients with spontaneous clearance, and 207 healthy controls. Three hundred fifty-seven CHC patients received recombinant interferon-alpha2b/ribavirin (IFN-α2b/RBV) treatment, and 175 patients were chosen for analysis of drug-induced cytopenia. All raw P-values were corrected by the Bonferroni method. Results: A higher rate of sustained viral response was detected in patients with SLC4A11 rs3810560 CC variant versus TT/TC variant (76.9% vs 59.2%; OR, 2.42; 95% CI, 1.06-5.56, P = 0.037 after adjustment), but there was no significant difference among different hepatitis C virus genotypes. RBV-induced anemia was independently correlated with SLC29A1 rs760370 AA genotype (OR, 2.90; 95% CI, 1.29-6.54, P = 0.010), and the severity of IFN-induced thrombocytopenia was related to GG genotype (OR, 4.98; 95% CI, 1.27-19.61; P = 0.021); the detected effects held true for HCV-2a patients but weakened in HCV-1b patients. A reactive increase in platelet count was closely associated with KLF12 rs9543524 TT variant. Conclusion: SLC4A11 rs3810560 polymorphism independently affected the sustained viral response rates in CHC patients, whereas SLC29A1 rs760370 and KLF12 rs9543524 single nucleotide polymorphisms correlated with treatment-induced adverse events. Clearly, the predictive power varied with HCV genotypes and the reason for genotype-dependent discrepancy was not fully understood.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%