Association of Mal/TIRAP S180L variant polymorphism with decreased infection risk in patients with advanced HIV-1 infection.
OBJECTIVE
MyD88 adaptor-like (Mal/TIRAP) is an adaptor protein bridging activation of Toll-like receptors 2 and 4 after stimulation by exogenous and endogenous ligands. We investigated the association between the presence of the S180L SNP of Mal and the risk of severe infection in individuals with human immunodeficiency virus (HIV)-1 infection.


METHODS
The SNP S180L was determined in a cohort of 179 HIV-1 infected Greek patients. Analysis of the prevalence of this SNP in relation to the infectious complications was evaluated.


RESULTS
One hundred and thirty-two (73.3%) patients were bearing the wild type haplotype, 43 (24%) were heterozygous for the SNP, and four (2.2%) were homozygous for the variant allele. The individuals with a nadir CD4 count <200 cells/mm(3) who carried the 180L variant demonstrated a 4-fold decrease in the odds ratio (OR) for any serious infection compared with those who carried the wild-type 180S genotype (OR 0.58 vs OR 2.6, p=0.016).


CONCLUSIONS
This study suggest a protection effect of the Mal S180L SNP against serious infections in HIV-1 infected individuals with low CD4 cell counts.
Fourth Department of Internal Medicine, University of Athens Medical School, Greece. antpapa1@otenet.gr
Antonios I
AI
Papadopoulos
Bart
B
Ferwerda
Anastasia
A
Antoniadou
Vissaria
V
Sakka
Lambrini
L
Galani
Dimitra
D
Kavatha
Periklis
P
Panagopoulos
Garyphalia
G
Poulakou
Konstantinos
K
Protopapas
Jos W M
JW
van der Meer
Mihai G
MG
Netea
Evangelos J
EJ
Giamarellos-Bourboulis
D000328:Adult; D019943:Amino Acid Substitution; D018791:CD4 Lymphocyte Count; D015331:Cohort Studies; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D015658:HIV Infections / Q000150:complications* / Q000276:immunology / Q000821:virology; D015497:HIV-1 / Q000276:immunology; D006239:Haplotypes; D006801:Humans; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics*; D008875:Middle Aged; D009894:Opportunistic Infections / Q000150:complications / Q000235:genetics* / Q000276:immunology; D020641:Polymorphism, Single Nucleotide; D017472:Receptors, Interleukin-1 / Q000235:genetics*; D012307:Risk Factors; D055815:Young Adult
D008562:Membrane Glycoproteins; D017472:Receptors, Interleukin-1; C434984:TIRAP protein, human