Vitamin D-binding protein gene polymorphisms may contribute to the racial disparity in genotype 1 chronic hepatitis C treatment outcome

Abstract

We read with great interest the study by Falleti et al. in which the authors report that the rs7041 G>T and rs4588 C>A single nucleotide polymorphisms (SNPs) of the vitamin D-binding protein gene are predictors of the treatment outcome of patients with chronic hepatitis C.1 The authors found that patients with any combination of three or more rs7041 G and rs4588 C alleles (wild type [WT+]) achieve a sustained virologic response (SVR) at a greater rate than patients with other genotypes (WT−). Additionally, they found that the relative frequency of the rs7041 T allele was increased significantly among the patients when compared with its frequency among healthy controls, raising the possibility that rs7041 T alleles are associated with increased susceptibility to infection or a lower rate of spontaneous viral clearance. Importantly, there is biologic plausibility for these findings in that each of the protein isoforms encoded by the variants of the vitamin D-binding protein gene studied by Falleti et al. differentially affect certain components of the immune response.2 In light of these findings, we sought to determine if there are racial differences in the distribution of the alleles of these SNPs among patients with chronic hepatitis C that could potentially contribute to the racial disparity in treatment outcome. We genotyped the rs7041 G>T and rs4588 C>A SNPs in 48 Caucasian and 95 African American genotype 1 chronic hepatitis C patients. Most notable were our findings concerning the rs7041 G>T SNP. The frequency of the rs7041 G>T alleles among the Caucasians was G = 0.542 and T = 0.458. This is similar to the frequency among the patients studied by Falleti et al., all of whom were Caucasian, of G = 0.553 and T = 0.447. However, the rs7041 G>T allele frequency among the African Americans we studied was G = 0.147 and T = 0.853, which is significantly different than that of the Caucasians we studied (P < 0.0001) and the patients studied by Falleti et al. (P < 0.0001). We then grouped our patients into the WT+ and WT− categories as defined by Falleti et al. (Table 1). Of the Caucasian patients we studied, 26/48 (54.2%) were WT+. This is similar to the finding by Falleti et al. that 100/206 (48.5%) of their patients were WT+. In contrast, however, only 25/95 (26.3%) of the African American patients in our study were WT+, which is significantly less than the frequency of the WT+ genotype in both our group of Caucasian patients (P = 0.0016) and the patients examined by Falleti et al. (P = 0.0003). Although our study was not sufficiently powered to confirm that vitamin D-binding protein genotype predicts antiviral treatment outcome independently of race, when considered with the findings of Falleti et al. our findings raise the possibility that racial variations in distribution of vitamin D-binding protein gene SNP alleles contribute to the racial disparity in treatment outcome in patients with chronic hepatitis C. Further studies are warranted. Acknowledgment: Supported by a grant from the Washington University School of Medicine Institute for Clinical and Translational Studies (to S.J.W.), the NIH (grants AI048216, AI066316, RR00211; to J.F.F., T.N.M., and M.A.M.) and the University of Tennessee Health Science Center Clinical and Translational Science Institute (to J.F.F., T.N.M., and M.A.M.). The Institute for Clinical and Translational Studies is supported by the NIH (grant RR024992). The University of Tennessee Cooperative Hepatitis C Center is a National Institute of Allergy and Infectious Diseases-sponsored cooperative center. Steven J. Weintraub, M.D.1,2Jaquelyn F. Fleckenstein, M.D.3,4Tony N. Marion, Ph.D.4,5Margaret A. Madey, B.S., R.N.6 1Department of Medicine Saint Louis Veterans Affairs Medical Center John Cochran Division St. Louis, MO2Department of Medicine Washington University School of Medicine St. Louis, MO3Division of Gastroenterology Department of Medicine Washington University School of Medicine St. Louis, MO4Hepatitis C Cooperative Research CenterUniversity of Tennessee Health Science Center Memphis, TN5Department of Molecular SciencesUniversity of Tennessee Health Science Center Memphis, TN6Department of Radiological Sciences St. Jude Children's Research Hospital Memphis, TN