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Polymorphisms of the SAMHD1 Gene Are Not Associated with the Infection and Natural Control of HIV Type 1 in Europeans and African-Americans
Journal article   Open access   Peer reviewed

Polymorphisms of the SAMHD1 Gene Are Not Associated with the Infection and Natural Control of HIV Type 1 in Europeans and African-Americans

Sirena Coon, Danxin Wang and Li Wu
AIDS research and human retroviruses, Vol.28(12), pp.1565-1573
12/01/2012
DOI: 10.1089/aid.2012.0039
PMCID: PMC3505062
PMID: 22530776
url
https://doi.org/10.1089/aid.2012.0039View
Published (Version of record) Open Access

Abstract

The HIV-1 restriction factor SAM domain and HD domain-containing protein 1 (SAMHD1) blocks HIV-1 infection in human myeloid cells. Mutations in the SAMHD1 gene are associated with rare genetic diseases including Aicardi–Goutieres syndrome. However, it is unknown whether polymorphisms of SAMHD1 are associated with infection and natural control of HIV-1 in humans. Our objective was to determine whether the expression of SAMHD1 mRNA is affected by common single nucleotide polymorphisms (SNPs) in SAMHD1 and whether the SNPs are associated with HIV-1 infection status. Using a tagging SNP approach, we determined the association between eight tagging SNPs in SAMHD1 and the mRNA expression in B-lymphocyte cell lines from 70 healthy white donors. We identified one SNP (rs1291142) that was significantly associated with SAMHD1 mRNA expression, with minor allele carriers having 30% less mRNA levels ( p =0.015). However, after analyzing the published genome-wide association study data of 857 HIV-1 controllers and 2088 HIV-1 progressors from the European and African-American cohorts, we did not find a significant association between SNPs in SAMHD1 and HIV-1 infection status, including SNP rs1291142 ( p >0.05). We also observed 2- to 6-fold variations of SAMHD1 mRNA levels in primary B-lymphocytes, CD4 + T-lymphocytes, and CD14 + monocytes from five healthy donors. Our results suggest that common regulatory polymorphism(s) exist in the SAMHD1 gene that affects its mRNA expression in B-lymphocyte cell lines from healthy whites. However, polymorphisms of SAMHD1 are unlikely to contribute to the infection and natural control of HIV-1 in European and African-American individuals.
Virology

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