Variation in human β-defensin genes: new insights from a multi-population study.
Variation in human β-defensin genes: new insights from a multi-population study.
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DOI：
10.1111/iji.12021
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发表时间：
2013-08
影响因子：
2.2
通讯作者：
Jurevic RJ
中科院分区：
文献类型：
--
作者：
Mehlotra RK;Zimmerman PA;Weinberg A;Jurevic RJ
分别由DEFB 4和DEFB 103 A编码的人β-防御素2（hBD-2）和hBD-3已显示出抗HIV活性，并且两个基因均表现出拷贝数变异（CNV）。虽然由DEFB 1编码的hBD-1在HIV-1感染中的作用尚不清楚，但DEFB 1中的单核苷酸多态性（SNP）可能影响病毒载量和疾病进展。我们研究了DEFB 1 SNP和DEFB 4/103 A CNV的分布，以及DEFB 1 SNP和DEFB 4/103 A CNV之间的关系，使用来自美国的两个HIV/AIDS队列（n = 150）和来自Coriell细胞库的五个不同人群（n = 46）的样本。我们使用后PCR，寡核苷酸连接检测反应-荧光微球测定法测定了DEFB 1中10个SNP的频率，并使用实时定量PCR测定了DEFB 4/103 A中的CNV。DEFB 1单倍型和等位基因频率在不同人种/民族之间存在显著差异。DEFB 4/103 A拷贝数从2到8不等（中位数，4），在美国队列中自我识别的白人和黑人的拷贝数之间存在显著差异（Mann-Whitney U检验p = 0.04）。DEFB 4/103 A CNV在DEFB 1 - 52 G/A和-390 T/A基因型间的分布差异有统计学意义（Kruskal-Wallis p值分别为0.017和0.026），而DEFB 4/103 A CNV在-52 G/A_-44 C/G_-20 G/A二倍型间的分布差异无统计学意义。这些观察结果为进一步研究β-防御素基因多态性与HIV感染/疾病的易感性或进展或严重程度之间的复杂相互作用提供了额外的见解。
Human β-defensin 2 (hBD-2) and hBD-3, encoded by DEFB4 and DEFB103A, respectively, have shown anti-HIV activity, and both genes exhibit copy number variation (CNV). Although the role of hBD-1, encoded by DEFB1, in HIV-1 infection is less clear, single nucleotide polymorphisms (SNPs) in DEFB1 may influence viral loads and disease progression. We examined the distribution of DEFB1 SNPs and DEFB4/103A CNV, and the relationship between DEFB1 SNPs and DEFB4/103A CNV using samples from two HIV/AIDS cohorts from the United States (n = 150) and five diverse populations from the Coriell Cell Repositories (n = 46). We determined the frequencies of 10 SNPs in DEFB1 by using a post-PCR, oligonucleotide ligation detection reaction-fluorescent microsphere assay, and CNV in DEFB4/103A by real-time quantitative PCR. There were noticeable differences in the frequencies of DEFB1 SNP alleles and haplotypes among various racial/ethnic groups. The DEFB4/103A copy numbers varied from 2 to 8 (median, 4), and there was a significant difference between the copy numbers of self-identified whites and blacks in the US cohorts (Mann-Whitney U test p = 0.04). A significant difference was observed in the distribution of DEFB4/103A CNV among DEFB1 -52G/A and -390T/A genotypes (Kruskal-Wallis p = 0.017 and 0.026, respectively), while not in the distribution of DEFB4/103A CNV among -52G/A_-44C/G_-20G/A diplotypes. These observations provide additional insights for further investigating the complex interplay between β-defensin genetic polymorphisms and susceptibility to, or the progression or severity of, HIV infection/disease.
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影响因子：
3.7
作者：
de Smith, Adam J.;Walters, Robin G.;Coin, Lachlan J. M.;Steinfeld, Israel;Yakhini, Zohar;Sladek, Rob;Froguel, Philippe;Blakemore, Alexandra I. F.
通讯作者：
Blakemore, Alexandra I. F.
影响因子：
9.8
作者：
Hollox, EJ;Armour, JAL;Barber, JCK
通讯作者：
Barber, JCK
影响因子：
3.9
作者：
Ferlin, Alberto;Ganz, Francesco;Foresta, Carlo
通讯作者：
Foresta, Carlo
影响因子：
3.8
作者：
Freguja, Riccardo;Gianesin, Ketty;De Rossi, Anita
通讯作者：
De Rossi, Anita
影响因子：
9.4
作者：
Jurevic, RJ;Bai, M;Dale, BA
通讯作者：
Dale, BA