TRIM5 gene polymorphisms in HIV-1-infected patients and healthy controls from Northeastern Brazil

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

Research output: Contribution to journalArticlepeer-review

Abstract

Humans show heterogeneity in vulnerability to HIV-1 infection, partially under control of genes involved in host immunity and virus replication. TRIM5α protein has restriction activity against replication of many retroviruses. Human TRIM5 gene single nucleotide polymorphisms have been reported as involved in susceptibility to HIV-1 infection. We recruited 213 HIV-1-positive patients and 234 healthy uninfected controls from Northeast Brazil; two non-synonymous variants at exon 2, rs3740996 (H43Y) and rs10838525 (R136Q), and one regulatory polymorphism (rs16934386) at 5′UTR region of TRIM5 were analyzed. The R136Q variation presented significant differences between HIV-1-positive patients and healthy controls. The 136Q allele and the 136QQ genotype were more frequent in healthy controls (32.7 and 10.2 %, respectively) than in HIV-1-positive patients (136Q allele: 24.4 %; OR 0.66; CI 95 % 0.49–0.90; p value = 0.008/136QQ genotype: 4.2 %; OR 0.33; CI 95 % 0.13–0.79, p = 0.008) also after adjusting for age and sex. We also stratified our findings according to the presence of CCR5Δ32 variation, but the results remained the same. We observed that rs10838525 (R136Q) and rs3740996 (H43Y) were in linkage disequilibrium (D′ = 0.71), forming four possible haplotypes. The H43–136Q haplotype was significantly more frequent in healthy controls (28.2 %) than in HIV-positive patients (21.4 %; OR 0.69; CI 95 % 0.50–0.96; p = 0.022). An increased frequency of allele (136Q) and genotype (136QQ) of the non-synonymous rs10838525 (R136Q) variant and the haplotype (43H-136Q) was observed among healthy controls individuals. Being aware of the limitation of this study (unavailability of exposed but uninfected individuals), we hypothesize a potential role for TRIM5 variations in the protection against HIV-1 infection.

Original languageEnglish
Pages (from-to)1-6
Number of pages6
JournalImmunologic Research
DOIs
Publication statusAccepted/In press - Jul 8 2016

Keywords

  • Association study
  • HIV-1
  • Host genetic variants
  • Restriction factors
  • Susceptibility to infection
  • TRIM5

ASJC Scopus subject areas

  • Immunology

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