title: Polymorphisms of the SAMHD1 gene are not associated with the infection and natural control of HIV type 1 in Europeans and African-Americans.
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.
authors.affiliation: Center for Retrovirus Research, Department of Veterinary Bioscience, The Ohio State University, Columbus, OH 43210, USA.
authors.forename: Sirena
authors.initials: S
authors.lastname: Coon
authors.forename: Danxin
authors.initials: D
authors.lastname: Wang
authors.forename: Li
authors.initials: L
authors.lastname: Wu
mesh_terms: D001741:Black or African American; D001402:B-Lymphocytes / Q000276:immunology; D020869:Gene Expression Profiling; D020022:Genetic Predisposition to Disease; D015658:HIV Infections / Q000235:genetics* / Q000276:immunology*; D006801:Humans; D020559:Monomeric GTP-Binding Proteins / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D000076106:SAM Domain and HD Domain-Containing Protein 1; D044465:White People
chemical_list: D000076106:SAM Domain and HD Domain-Containing Protein 1; C484280:SAMHD1 protein, human; D020559:Monomeric GTP-Binding Proteins