Host genetic factors and vaccine-induced immunity to HBV infection: haplotype analysis.
Host genetic factors and vaccine-induced immunity to HBV infection: haplotype analysis.
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DOI：
10.1371/journal.pone.0012273
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发表时间：
2010-08-18
期刊：
影响因子：
3.7
通讯作者：
Hennig BJ
中科院分区：
文献类型：
--
作者：
Ryckman KK;Fielding K;Hill AV;Mendy M;Rayco-Solon P;Sirugo G;van der Sande MA;Waight P;Whittle HC;Hall AJ;Williams SM;Hennig BJ
B型肝炎病毒（HBV）感染仍然是世界范围内的重大健康负担，尽管疫苗有助于减少这一问题。我们以前确定了几个候选基因的单核苷酸多态性与疫苗诱导的峰值抗体水平（抗-HBs）的关联，这是预测长期疫苗有效性和预防感染和持续携带的保护;在这里，我们报告了基于单体型的分析。在冈比亚队列中，对来自117个基因的688个SNP进行了2、3和4滑动窗口单倍型分析。对197个无关个体、来自174个家庭的454个个体和合并样本（N = 651）进行了分析。 采用抗-HBs峰值水平作为结果，进行总体和个体单倍型关联检验（调整协变量）。5个基因（CD 44、CD 58、CDC 42、IL 19和IL 1 R1）在无关或家系分析以及联合分析中至少有一个显著的单倍型。之前的单基因座结果得到了证实，包括CD 44（rs353644-rs353630-rs7937602的组合全局p=9.1×10−5）和CD 58（ rs 1414275-rs 11588376-rs 1016140的组合全局p=0.008）。 CDC 42、IL 19和IL 1 R1单倍型也与抗-HBs峰值水平相关。我们已经在五个基因中确定了对HBV疫苗诱导的抗体水平的强烈单倍型效应，其中三个基因，CDC 42，IL 19和IL 1 R1，在单个SNP分析中没有显示出关联的证据，并在两个数据集中证实了这些效应的大部分。单倍型分析确定了几个新基因与HBV疫苗诱导的免疫相关。
Hepatitis B virus (HBV) infection remains a significant health burden world-wide, although vaccines help decrease this problem. We previously identified associations of single nucleotide polymorphisms in several candidate genes with vaccine-induced peak antibody level (anti-HBs), which is predictive of long-term vaccine efficacy and protection against infection and persistent carriage; here we report on a haplotype-based analysis. A total of 688 SNPs from 117 genes were examined for a two, three and four sliding window haplotype analysis in a Gambian cohort. Analysis was performed on 197 unrelated individuals, 454 individuals from 174 families, and the combined sample (N = 651). Global and individual haplotype association tests were carried out (adjusted for covariates), employing peak anti-HBs level as outcome. Five genes (CD44, CD58, CDC42, IL19 and IL1R1) had at least one significant haplotype in the unrelated or family analysis as well as the combined analysis. Previous single locus results were confirmed for CD44 (combined global p = 9.1×10−5 for rs353644-rs353630-rs7937602) and CD58 (combined global p = 0.008 for rs1414275-rs11588376-rs1016140). Haplotypes in CDC42, IL19 and IL1R1 also associated with peak anti-HBs level. We have identified strong haplotype effects on HBV vaccine-induced antibody level in five genes, three of which, CDC42, IL19 and IL1R1, did not show evidence of association in a single SNP analyses and corroborated the majority of these effects in two datasets. The haplotype analysis identified associations with HBV vaccine-induced immunity in several new genes.
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影响因子：
6.4
作者：
van der Sande, MAB;Waight, P;Whittle, HC
通讯作者：
Whittle, HC
影响因子：
4.6
作者：
Kruger, A;Adams, P;Hoehler, T
通讯作者：
Hoehler, T
DOI：
10.1111/j.2517-6161.1995.tb02031.x
发表时间：
1995-01-01
影响因子：
5.8
作者：
BENJAMINI, Y;HOCHBERG, Y
通讯作者：
HOCHBERG, Y
影响因子：
56.9
作者：
Gabriel, SB;Schaffner, SF;Altshuler, D
通讯作者：
Altshuler, D
影响因子：
5
作者：
Davila, S.;Froeling, F. E. M.;Seielstad, M.
通讯作者：
Seielstad, M.