Vitamin D-binding protein gene polymorphisms may contribute to the racial disparity in genotype 1 chronic hepatitis C treatment outcome.
Vitamin D-binding protein gene polymorphisms may contribute to the racial disparity in genotype 1 chronic hepatitis C treatment outcome.
复制标题
维生素 D 结合蛋白基因多态性可能导致基因 1 型慢性丙型肝炎治疗结果的种族差异。
DOI：
10.1002/hep.26432
复制
发表时间：
2013
期刊：
影响因子：
--
通讯作者：
Madey,MargaretA
中科院分区：
文献类型：
--
作者：
Weintraub,StevenJ;Fleckenstein,JaquelynF;Marion,TonyN;Madey,MargaretA
我们怀着极大的兴趣阅读了法莱蒂等人的研究报告。其中，作者报道了维生素D结合蛋白基因的rs7041 G>；T和rs4588 C>；A单核苷酸多态(SNPs)是预测慢性丙型肝炎患者治疗结果的指标。1作者发现，rs7041 G和rs4588 C等位基因(野生型[WT1])任意组合的患者获得持续病毒学应答(SVR)的比率高于其他基因型(WT2)的患者。此外，他们发现，与健康对照组相比，患者中rs7041T等位基因的相对频率显著增加，这增加了rs7041T等位基因与感染易感性增加或病毒自发清除率较低相关的可能性。重要的是，这些发现有生物学上的合理性，因为每一种蛋白质亚型都是由Falleti等人研究的维生素D结合蛋白基因的变体编码的。以不同的方式影响免疫反应的某些组成部分。2根据这些发现，我们试图确定这些SNPs在慢性丙型肝炎患者中的等位基因分布是否存在种族差异，这可能导致治疗结果的种族差异。我们对48例高加索人和95例非裔美国人慢性丙型肝炎患者的rs7041 G>；T和rs4588 C>；A SNPs进行了基因分型。最值得注意的是我们关于rs7041G>；T SNP的发现。高加索人群中rs7041G>；T等位基因频率为G5 0.542，T5 0.458。这与Falleti等人研究的全部为高加索人的患者中G5 0.553和T5 0.447的频率相似。然而，在我们研究的非裔美国人中，rs7041G>；T等位基因频率为G5 0.147和T50。853，这与我们研究的高加索人(P<；0.0001)和Falleti等人研究的患者(P<；0.0001)有显著差异。然后，我们按照Falleti等人的定义将我们的患者分为WT1和WT2两类(表1)。在我们研究的高加索患者中，26/48(54.2%)是WT1。这与Falleti等人的发现类似。206例患者中有100例(48.5%)为WT1。然而，相比之下，在我们的研究中，只有25/95的非裔美国人患者(26.3%)是WT1，这明显低于我们的高加索患者组(P5 0.0016)和Falleti等人检查的患者(P50)。0003)。尽管我们的研究还不足以证实维生素D结合蛋白基因与种族无关地预测抗病毒治疗结果，但考虑到Falleti等人的发现。我们的发现提高了维生素D结合蛋白基因SNP等位基因分布的种族差异导致慢性丙型肝炎患者治疗结果种族差异的可能性。进一步的研究是有必要的。认可：得到了华盛顿大学医学院临床和翻译研究研究所(TO SJW)、NIH(拨款AI048216、AI066316、RR00211；拨款给JFF、TNM和MAM)和田纳西大学健康科学中心临床和翻译科学研究所(TFF、TNM和MAM)的资助。临床和翻译研究所由美国国立卫生研究院资助(拨款RR024992)。田纳西大学丙型肝炎合作中心是由国家过敏和传染病研究所赞助的合作中心。
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 [WT1]) achieve a sustained virologic response (SVR) at a greater rate than patients with other genotypes (WT2). 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 G5 0.542 and T5 0.458. This is similar to the frequency among the patients studied by Falleti et al., all of whom were Caucasian, of G5 0.553 and T5 0.447. However, the rs7041 G> T allele frequency among the African Americans we studied was G5 0.147 and T50. 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 WT1 and WT2 categories as defined by Falleti et al.(Table 1). Of the Caucasian patients we studied, 26/48 (54.2%) were WT1. This is similar to the finding by Falleti et al. that 100/206 (48.5%) of their patients were WT1. In contrast, however, only 25/95 (26.3%) of the African American patients in our study were WT1, which is significantly less than the frequency of the WT1 genotype in both our group of Caucasian patients (P5 0.0016) and the patients examined by Falleti et al.(P50. 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 SJW), the NIH (grants AI048216, AI066316, RR00211; to JFF, TNM, and MAM) and the University of Tennessee Health Science Center Clinical and Translational Science Institute (to JFF, TNM, and MAM). 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 Diseasessponsored cooperative center.