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与巴西东北部HIV-1感染个体病毒载量水平升高相关的HLA-C单核苷酸多态性

HLA-C Single Nucleotide Polymorphism Associated with Increased Viral Load Level in HIV-1 Infected Individuals from Northeast Brazil.

作者信息

Celerino da Silva Ronaldo, Moura Ronald Rodrigues, Victor Campos Coelho Antonio, Arraes Luiz Cláudio, Brandão Lucas André Cavalcanti, Crovella Sergio, Lima Guimarães Rafael

机构信息

Department of Genetics, Federal University of Pernambuco (UFPE), Recife. Brazil.

Institute of Integral Medicine of Pernambuco Professor Fernando Figueira, Recife, Brazil.

出版信息

Curr HIV Res. 2017;15(4):266-272. doi: 10.2174/1570162X15666170511141741.

Abstract

BACKGROUND

Genetic variations in Human leukocyte antigen C (HLA-C), Zinc ribbon domain containing 1 (ZNRD1) and its antisense RNA (ZNRD1-AS1) genes are known to influence the HIV-1 replication and disease progression.

OBJECTIVE AND METHOD

We evaluated the distribution of HLA-C (rs10484554, rs9264942) and ZNRD1 (rs8321) and ZNRD1-AS1 (rs3869068), single nucleotide polymorphisms (SNPs) in 266 HIV-1-infected and 223 unexposed-uninfected individuals from Northeast Brazil and their relation to HIV-1 infection, CD4 T cells count and viral load pre-treatment.

RESULTS

HLA-C SNPs were in Linkage Disequilibrium (D'=0.84), constituting four possible haplotypes. Our results showed that HLA-C, ZNRD1 and ZNRD1-AS1 SNPs as well as HLA-C haplotypes frequencies were not significantly different between HIV-1-infected and unexposed-uninfected individuals. In addition, we analyzed HLA-C and ZNRD-1 and ZNRD1-AS1 SNPs considering CD4+ T cell counts and viral load before the antiretroviral treatment. Individuals carrying HLA-C rs9264942 TT genotype showed a significant increased level of HIV-1 viral load pre-treatment, in comparison with individuals carrying the CC genotype (p-value = 0.0092). Finally, we stratified our findings according to CCR5Δ32 allele presence along with the studied SNPs: no statistically significant influence over viral load pre-treatment has been found.

CONCLUSION

The association between HLA-C rs9264942 SNP and viral load prior treatment in an admixed population from North East Brazil was in agreement with findings from previous studies obtained on different ethnic groups; however more studies should be conducted in order to clarify how HLA-C impair the HIV-1 replication.

摘要

背景

已知人类白细胞抗原C(HLA - C)、含锌带结构域1(ZNRD1)及其反义RNA(ZNRD1 - AS1)基因的遗传变异会影响HIV - 1复制和疾病进展。

目的和方法

我们评估了来自巴西东北部的266名HIV - 1感染者和223名未暴露未感染个体中HLA - C(rs10484554、rs9264942)、ZNRD1(rs8321)和ZNRD1 - AS1(rs3869068)单核苷酸多态性(SNP)的分布,以及它们与HIV - 1感染、治疗前CD4 T细胞计数和病毒载量的关系。

结果

HLA - C SNP处于连锁不平衡状态(D' = 0.84),构成四种可能的单倍型。我们的结果表明,HIV - 1感染者和未暴露未感染个体之间HLA - C、ZNRD1和ZNRD1 - AS1 SNP以及HLA - C单倍型频率没有显著差异。此外,我们在抗逆转录病毒治疗前考虑CD4 + T细胞计数和病毒载量分析了HLA - C、ZNRD - 1和ZNRD1 - AS1 SNP。与携带CC基因型的个体相比,携带HLA - C rs9264942 TT基因型的个体治疗前HIV - 1病毒载量显著升高(p值 = 0.0092)。最后,我们根据CCR5Δ32等位基因的存在以及所研究的SNP对我们的发现进行分层:未发现对治疗前病毒载量有统计学显著影响。

结论

巴西东北部一个混合人群中HLA - C rs9264942 SNP与治疗前病毒载量之间的关联与先前在不同种族群体中获得的研究结果一致;然而,需要进行更多研究以阐明HLA - C如何损害HIV - 1复制。

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