title: Variants in the CYP7B1 gene region do not affect natural resistance to HIV-1 infection.
abstract: BACKGROUND
  The genetic bases of natural resistance to HIV-1 infection remain largely unknown. Recently, two genome-wide association studies suggested a role for variants within or in the vicinity of the CYP7B1 gene in modulating HIV susceptibility. CYP7B1 is an appealing candidate for this due to its contribution to antiviral immune responses. We analyzed the frequency of two previously described CYP7B1 variants (rs6996198 and rs10808739) in three independent cohorts of HIV-1 infected subjects and HIV-1 exposed seronegative individuals (HESN).
  
  
  RESULTS
  rs6996198 and rs10808739 were genotyped in three case/control cohorts of sexually-exposed HESN and HIV-1-infected individuals from Italy, Peru and Colombia. Comparison of the allele and genotype frequencies of the two SNPs under different models showed that the only significant difference was seen for rs6996198 in the Peruvian sample (nominal p = 0.048, dominant model). For this variant, a random-effect meta-analysis yielded non-significant results (dominant model, p = 0.78) and revealed substantial heterogeneity among cohorts. No significant effect of the rs10808739 allelic status on HIV-1 infection susceptibility (additive model, p = 0.30) emerged from the meta-analysis.
  
  
  CONCLUSIONS
  Although our study had limited power to detect association due to the small sample size, comparisons among the three cohorts revealed very similar allelic and genotypic frequencies in HESN and HIV-1 positive subjects. Overall, these data indicate that the two GWAS-defined variants in the CYP7B1 region do not strongly influence HIV-1 infection susceptibility.
authors.affiliation: Scientific Institute IRCCS E. MEDEA, Bioinformatics, 23842, Bosisio Parini, Italy. msironi@bp.lnf.it.
authors.forename: Manuela
authors.initials: M
authors.lastname: Sironi
authors.affiliation: Department of Biomedical and Clinical Sciences "L. Sacco", University of Milan, Via G.B. Grassi 74, 20157, Milan, Italy. mara.biasin@unimi.it.
authors.forename: Mara
authors.initials: M
authors.lastname: Biasin
authors.affiliation: Scientific Institute IRCCS E. MEDEA, Bioinformatics, 23842, Bosisio Parini, Italy. chiara.pontremoli@bp.lnf.it.
authors.forename: Chiara
authors.initials: C
authors.lastname: Pontremoli
authors.affiliation: Scientific Institute IRCCS E. MEDEA, Bioinformatics, 23842, Bosisio Parini, Italy. rachele.cagliani@bp.lnf.it.
authors.forename: Rachele
authors.initials: R
authors.lastname: Cagliani
authors.affiliation: Department of Biomedical and Clinical Sciences "L. Sacco", University of Milan, Via G.B. Grassi 74, 20157, Milan, Italy. irma.saulle@unimi.it.
authors.forename: Irma
authors.initials: I
authors.lastname: Saulle
authors.affiliation: Department of Biomedical and Clinical Sciences "L. Sacco", University of Milan, Via G.B. Grassi 74, 20157, Milan, Italy. daria.trabattoni@unimi.it.
authors.forename: Daria
authors.initials: D
authors.lastname: Trabattoni
authors.affiliation: S. Maria Annunziata Hospital, 50122, Florence, Italy. francesca.vichi@asf.toscana.it.
authors.forename: Francesca
authors.initials: F
authors.lastname: Vichi
authors.affiliation: S. Maria Annunziata Hospital, 50122, Florence, Italy. sergio.locaputo@asf.toscana.it.
authors.forename: Sergio
authors.initials: S
authors.lastname: Lo Caputo
authors.affiliation: S. Maria Annunziata Hospital, 50122, Florence, Italy. francesco.mazzotta@asf.toscana.it.
authors.forename: Francesco
authors.initials: F
authors.lastname: Mazzotta
authors.affiliation: Immunovirology Group, School of Medicine, University of Antioquia UdeA, Medellín, Colombia. aguilar.wb@gmail.com.
authors.forename: Wbeimar
authors.initials: W
authors.lastname: Aguilar-Jimenez
authors.affiliation: Immunovirology Group, School of Medicine, University of Antioquia UdeA, Medellín, Colombia. maria.rugeles@udea.edu.co.
authors.forename: Maria Teresa
authors.initials: MT
authors.lastname: Rugeles
authors.affiliation: AIDS Research Institute-IrsiCaixa-HIVACAT, Hospital Germans Trias i Pujol, Universitat Autònoma de Barcelona, Badalona, Institució Catalana de Recerca i Estudis Avançats (ICREA), Barcelona, Spain. SCedeno@irsicaixa.es.|University of Vic and Central Catalonia, Vic, Spain. SCedeno@irsicaixa.es.
authors.forename: Samandhy
authors.initials: S
authors.lastname: Cedeno
authors.affiliation: Asociación Civil Impacta Salud y Educación, Lima, Peru. jsanchez@impactaperu.org.
authors.forename: Jorge
authors.initials: J
authors.lastname: Sanchez
authors.affiliation: AIDS Research Institute-IrsiCaixa-HIVACAT, Hospital Germans Trias i Pujol, Universitat Autònoma de Barcelona, Badalona, Institució Catalana de Recerca i Estudis Avançats (ICREA), Barcelona, Spain. cbrander@irsicaixa.es.|University of Vic and Central Catalonia, Vic, Spain. cbrander@irsicaixa.es.
authors.forename: Christian
authors.initials: C
authors.lastname: Brander
authors.affiliation: Department of Physiopathology and Transplantation, University of Milan, 20090, Milan, Italy. mario.clerici@unimi.it.|Don C. Gnocchi Foundation ONLUS, IRCCS, 20148, Milan, Italy. mario.clerici@unimi.it.
authors.forename: Mario
authors.initials: M
authors.lastname: Clerici
mesh_terms: D000328:Adult; D000483:Alleles; D000072474:Cytochrome P450 Family 7; D005260:Female; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D005838:Genotype; D015658:HIV Infections / Q000235:genetics* / Q000276:immunology* / Q000821:virology; D015497:HIV-1 / Q000502:physiology; D006801:Humans; D007113:Immunity, Innate / Q000235:genetics*; D008297:Male; D020641:Polymorphism, Single Nucleotide; D013250:Steroid Hydroxylases / Q000235:genetics*
chemical_list: D013250:Steroid Hydroxylases; D000072474:Cytochrome P450 Family 7; C499571:CYP7B1 protein, human