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Variants in the CYP7B1 gene region do not affect natural resistance to HIV-1 infection.

Sironi M, Biasin M, Pontremoli C, Cagliani R, Saulle I, Trabattoni D, Vichi F, Lo Caputo S, Mazzotta F, Aguilar-Jimenez W, Rugeles MT, Cedeno S, Sanchez J, Brander C, Clerici M - Retrovirology (2015)

Bottom Line: CYP7B1 is an appealing candidate for this due to its contribution to antiviral immune responses.For this variant, a random-effect meta-analysis yielded non-significant results (dominant model, p = 0.78) and revealed substantial heterogeneity among cohorts.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.

View Article: PubMed Central - PubMed

Affiliation: Scientific Institute IRCCS E. MEDEA, Bioinformatics, 23842, Bosisio Parini, Italy. msironi@bp.lnf.it.

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).

Findings: 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.

No MeSH data available.


Related in: MedlinePlus

Analyzed variants and LD analysis. Representation of the CYP7B1 gene region within the UCSC Genome Browser view. The two variants we genotyped are shown in red. Variants in LD (r2 ≥ 0.8) with rs10808739 in Africans, Americans, and Europeans are reported in blue. SNPs in green show LD (r2 ≥ 0.8) with rs10808739 in African populations only. Relevant ENCODE regulation tracks are shown
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Fig1: Analyzed variants and LD analysis. Representation of the CYP7B1 gene region within the UCSC Genome Browser view. The two variants we genotyped are shown in red. Variants in LD (r2 ≥ 0.8) with rs10808739 in Africans, Americans, and Europeans are reported in blue. SNPs in green show LD (r2 ≥ 0.8) with rs10808739 in African populations only. Relevant ENCODE regulation tracks are shown

Mentions: The original study that reported association of rs6996198 with protection from HIV-1 acquisition was performed in European populations; analysis of the 1000 Genomes Project data (Phase I) indicated that no variant in strong LD (r2 ≥ 0.8) with rs6996198 segregates in Europeans (nor in Americans). As for rs10808739, it was initially described in cohorts of African ancestry. LD analysis in African populations indicated that rs10808739 is in strong LD (r2 ≥ 0.8) with several variants, the majority of which show a similar LD pattern in Europeans and Americans (Fig. 1). Thus, it seems unlikely that the negative results we obtained are due to substantially different haplotype structures across populations.Fig. 1


Variants in the CYP7B1 gene region do not affect natural resistance to HIV-1 infection.

Sironi M, Biasin M, Pontremoli C, Cagliani R, Saulle I, Trabattoni D, Vichi F, Lo Caputo S, Mazzotta F, Aguilar-Jimenez W, Rugeles MT, Cedeno S, Sanchez J, Brander C, Clerici M - Retrovirology (2015)

Analyzed variants and LD analysis. Representation of the CYP7B1 gene region within the UCSC Genome Browser view. The two variants we genotyped are shown in red. Variants in LD (r2 ≥ 0.8) with rs10808739 in Africans, Americans, and Europeans are reported in blue. SNPs in green show LD (r2 ≥ 0.8) with rs10808739 in African populations only. Relevant ENCODE regulation tracks are shown
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4581478&req=5

Fig1: Analyzed variants and LD analysis. Representation of the CYP7B1 gene region within the UCSC Genome Browser view. The two variants we genotyped are shown in red. Variants in LD (r2 ≥ 0.8) with rs10808739 in Africans, Americans, and Europeans are reported in blue. SNPs in green show LD (r2 ≥ 0.8) with rs10808739 in African populations only. Relevant ENCODE regulation tracks are shown
Mentions: The original study that reported association of rs6996198 with protection from HIV-1 acquisition was performed in European populations; analysis of the 1000 Genomes Project data (Phase I) indicated that no variant in strong LD (r2 ≥ 0.8) with rs6996198 segregates in Europeans (nor in Americans). As for rs10808739, it was initially described in cohorts of African ancestry. LD analysis in African populations indicated that rs10808739 is in strong LD (r2 ≥ 0.8) with several variants, the majority of which show a similar LD pattern in Europeans and Americans (Fig. 1). Thus, it seems unlikely that the negative results we obtained are due to substantially different haplotype structures across populations.Fig. 1

Bottom Line: CYP7B1 is an appealing candidate for this due to its contribution to antiviral immune responses.For this variant, a random-effect meta-analysis yielded non-significant results (dominant model, p = 0.78) and revealed substantial heterogeneity among cohorts.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.

View Article: PubMed Central - PubMed

Affiliation: Scientific Institute IRCCS E. MEDEA, Bioinformatics, 23842, Bosisio Parini, Italy. msironi@bp.lnf.it.

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).

Findings: 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.

No MeSH data available.


Related in: MedlinePlus