Genomic approach of AIDS pathogenesis: exhaustive genotyping of the TNFR1 gene in a French AIDS cohort.
Large-scale genomic studies in cohorts have been made possible for the last few years thanks to the progress of molecular biology and bioinformatics. This systematic approach allows a better understanding of the molecular mechanisms of disease development and as a consequence can contribute to the rational design of new diagnostic and therapeutic tools. We present here the exhaustive genotyping of a candidate gene, tumor necrosis factor receptor 1 (TNFR1), in the genetic of resistance to immunodeficiency virus (GRIV) AIDS cohort. This gene was chosen because it is likely to be involved in the apoptosis pathways of CD4+ and CD8+ T-cells during human immunodeficiency virus 1 (HIV-1) infection. Seven frequent polymorphisms were characterized in 319 HIV-1 seropositive patients from the GRIV cohort with extreme disease progression phenotypes, slow progression or rapid progression, and in 427 healthy controls. The TNFR1 gene locus does not appear to be part of any haploblock and contains only a small haploblock of two successive SNPs. One promoter SNP (TNFR1_17444594, position -581) and one intronic SNP (TNFR1_27223241, position +11511) gave weak positive signals of association (resp. P=0.03 and P=0.04) as well as two haplotypes. To our knowledge, this is the first genetic association study dealing with the TNFR1 gene in AIDS and the putative associations identified will need to be validated through other AIDS cohort analyses or by further biological experimentation.
Diop
Gora
G
Equipe génomique, bioinformatique et pathologies du système immunitaire, Inserm EMI0355, 15, rue de l'Ecole-de-Médecine, 75006 Paris, France.
Spadoni
Jean-Louis
JL
Do
Hervé
H
Hirtzig
Thomas
T
Coulonges
Cédric
C
Labib
Taoufik
T
Issing
Wolfgang
W
Rappaport
Jay
J
Therwath
Amu
A
Lathrop
Mark
M
Matsuda
Fumihiko
F
Zagury
Jean-François
JF
D000163:Acquired Immunodeficiency Syndrome / Q000235:genetics* / Q000473:pathology; D015331:Cohort Studies; D018450:Disease Progression; D004198:Disease Susceptibility; D005602:France; D005787:Gene Frequency; D023281:Genomics; D005838:Genotype; D006679:HIV Seropositivity; D015497:HIV-1; D006801:Humans; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000235:genetics*; D044465:White People
D047888:Receptors, Tumor Necrosis Factor, Type I