Association of single-nucleotide polymorphisms in TLR7 (Gln11Leu) and TLR9 (1635A/G) with a higher CD4T cell count during HIV infection

E A Said; F Al-Yafei; F Zadjali; S S Hasson; M S Al-Balushi; S Al-Mahruqi; C Y Koh; K Al-Naamani; J Z Al-Busaidi; M A Idris; A Balkhair; A A Al-Jabri

doi:10.1016/j.imlet.2014.04.005

Association of single-nucleotide polymorphisms in TLR7 (Gln11Leu) and TLR9 (1635A/G) with a higher CD4T cell count during HIV infection

Immunol Lett. 2014 Jul;160(1):58-64. doi: 10.1016/j.imlet.2014.04.005. Epub 2014 Apr 16.

Authors

E A Said¹, F Al-Yafei², F Zadjali³, S S Hasson², M S Al-Balushi², S Al-Mahruqi², C Y Koh², K Al-Naamani⁴, J Z Al-Busaidi², M A Idris², A Balkhair⁵, A A Al-Jabri²

Affiliations

¹ Department of Microbiology and Immunology, College of Medicine and Health Sciences, Sultan Qaboos University, P.O. Box: 35, Code: 123, Muscat, Oman. Electronic address: elias.said@gmail.com.
² Department of Microbiology and Immunology, College of Medicine and Health Sciences, Sultan Qaboos University, P.O. Box: 35, Code: 123, Muscat, Oman.
³ Department of Biochemistry, College of Medicine and Health Sciences, Sultan Qaboos University, P.O. Box: 35, Code: 123, Muscat, Oman.
⁴ Department of Hepatology, Armed Forces Hospital, Muscat, Oman.
⁵ Department of Medicine, College of Medicine and Health Sciences, Sultan Qaboos University, P.O. Box: 35, Code: 123, Muscat, Oman.

PMID: 24747071
DOI: 10.1016/j.imlet.2014.04.005

Abstract

Background: Toll-like receptors (TLRs) are essential elements of the innate immune response to different infections including HIV-1 infection. The single-nucleotide polymorphisms (SNPs) in TLRs have been associated with CD4T cell count and HIV disease progression. The TLR7 (Gln11Leu) SNP was shown to be associated with a rapid decline of CD4T cell count. A relation between TLR9 (1635A/G) SNP and CD4T cells count in HIV-infected patients is suggested, although the outcome associated with this SNP is still controversial.

Objectives: To determine the relation of the TLR7 (Gln11Leu) and TLR9 (1635A/G) SNPs with the damage to the immune system during HIV infection as reflected by the average CD4T cell count.

Methods: A total of 63 HIV-infected patients and 100 healthy individuals (controls) were enrolled in this study. The above named SNPs were analyzed after amplification of the regions that potentially contain the SNPs by polymerase chain reaction (PCR) and sequencing of the PCR products. The frequency of these SNPs and their relation with the CD4T cell count were investigated.

Results: The TLR7 (AA) genotype 'Gln' had a trend toward being associated with a CD4T cell count >400cells/μl after controlling viremia via HAART. Additionally, the TLR9 1635 (GG) genotype was associated with a low average CD4T cell count and the TLR9 1635 (AG) genotype was significantly related to a higher average CD4T cell count during the viremic period in HIV-infected patients.

Conclusion: The results of this longitudinal study supports the presence of an association between the TLR9 (1635A/G) genotype and the CD4T cell count, which helps clarifying the controversial results regarding this association. It also suggests that the CD4T cell count during the viremic period might be linked to the combination of both TLR7 (Gln11Leu) and TLR9 (1635A/G) genotypes. These results may help predicting the damage to the immune system, and thus impacting the planning for novel anti-HIV strategies.

Keywords: CD4T cells; HIV; Single nucleotide polymorphism (SNP); Toll-like receptor; Viremic.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adult
Alleles
Amino Acid Substitution
Antiretroviral Therapy, Highly Active
CD4 Lymphocyte Count*
Case-Control Studies
Female
Gene Frequency
Genotype
HIV Infections / drug therapy
HIV Infections / genetics*
HIV Infections / immunology*
HIV Infections / virology
HIV-1 / immunology*
Humans
Male
Middle Aged
Polymorphism, Single Nucleotide*
Toll-Like Receptor 7 / genetics*
Toll-Like Receptor 9 / genetics*
Viral Load

Substances

Toll-Like Receptor 7
Toll-Like Receptor 9