Affiliations: School of Pathology and Laboratory Medicine,
University of Western Australia, Nedlands, WA, Australia | Department of Laboratory Medicine, All India Institute
of Medical Sciences, New Delhi, India | Lala Ram Sarup Institute of Tuberculosis {and}
Respiratory Diseases, New Delhi, India
Note: [] Corresponding author: Patricia Price, School of Pathology and
Laboratory Medicine, University of Western Australia, Nedlands WA 6009,
Australia. Tel.: +61 8 9224 0378; Fax: +61 8 9224 0204; E-mail:
patricia.price@uwa.edu.au
Abstract: BACKGROUND: Up to 43% of HIV-infected patients co-infected with
Mycobacterium tuberculosis experience exacerbations of tuberculosis (TB) after
commencing antiretroviral therapy (ART). These are termed immune restoration
disease (IRD). It is unclear why individual susceptibility varies. OBJECTIVE: We investigate if single nucleotide polymorphisms (SNP)
in genes encoding cytokines, chemokines and their receptors associate with
development of an IRD event in patients of two different ethnicities. METHODS: DNA samples were available from small well-characterised
groups of HIV patients treated in Cambodia (TB-IRD, n=17;
HIV^{+}TB^{+} controls, n=55) and India
(TB-IRD, n=19; HIV^{+}TB^{+} controls, n=
43). HIV patients with a TB diagnosis but no evidence of IRD were included to
control for susceptibility to TB per se. Sixteen SNP implicated in inflammation
or mycobacterial disease were genotyped. RESULTS: Susceptibility to TB-IRD associated with carriage of
TNFA-1031*T (rs1799964; P=0.05) and SLC11A1 D543N*G (rs17235409; P=0.04) in
Cambodian patients and carriage of IL18-607*G (rs1946518; P=0.02) and VDR FokI
(F/f)*T (rs10735810; P=0.05) in Indian patients. CONCLUSIONS: Associations between polymorphisms in immune-related
genes and TB-IRD were found, but none were common across two ethnicities.
Keywords: TB-IRD susceptibility, immunogenetic factor, single nucleotide polymorphism
