Association of SLC11A1 with tuberculosis and interactions with NOS2A and TLR2 in African-Americans and Caucasians.
METHODS
Host defense factors may influence the development of active tuberculosis (TB).


OBJECTIVE
To test variants in solute carrier family 11A, member 1 (SLC11A1), for an association with TB.


METHODS
A mixed case-control study of TB cases, relatives or close contact controls, consisting of 474 African-Americans (243 families) and 381 Caucasians (192 families), examined 13 SLC11A1 polymorphisms for association with pulmonary TB using generalized estimating equations adjusting for age and sex.


RESULTS
Two associations were observed in Caucasians (rs3731863, P = 0.03, and rs17221959, P = 0.04) and one in African-Americans (rs3731865, P = 0.05). Multilocus analyses between polymorphisms in SLC11A1 and 11 TB candidate genes detected interactions between SLC11A1 and inducible nitric oxide synthase (NOS2A) in Caucasians (rs3731863 [SLC11A1] x rs8073782 [NOS2A], P = 0.009; rs3731863 [SLC11A1] x rs17722851 [NOS2A], P = 0.007) and toll-like receptor 2 (TLR2) in African-Americans (rs3731865 [SLC11A1] x rs1816702, P = 0.005).


CONCLUSIONS
No association was detected with 5'(GT)(n) promoter polymorphism previously associated with lower SLC11A1 expression, rs17235409 (D543N), or rs17235416 (3' TGTG insertion/deletion polymorphism). SLC11A1 polymorphism rs3731865 was associated with TB in African-Americans, consistent with previous findings in West Africans. These results suggest that variants in SLC11A1 increase susceptibility to pulmonary TB and interact with other variants that differ by race.
Velez
D R
DR
Dr John T Macdonald Foundation Department of Human Genetics & Miami Institute of Human Genomics, Miller School of Medicine, University of Miami, Miami, Florida, USA.
Hulme
W F
WF
Myers
J L
JL
Stryjewski
M E
ME
Abbate
E
E
Estevan
R
R
Patillo
S G
SG
Gilbert
J R
JR
Hamilton
C D
CD
Scott
W K
WK
D000293:Adolescent; D000328:Adult; D001741:Black or African American / Q000235:genetics*; D000368:Aged; D001118:Argentina; D016022:Case-Control Studies; D027682:Cation Transport Proteins / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D007113:Immunity, Innate / Q000235:genetics; D008297:Male; D008875:Middle Aged; D052247:Nitric Oxide Synthase Type II / Q000235:genetics*; D009657:North Carolina; D016017:Odds Ratio; D010375:Pedigree; D020641:Polymorphism, Single Nucleotide; D051195:Toll-Like Receptor 2 / Q000235:genetics*; D014376:Tuberculosis / Q000201:enzymology / Q000208:ethnology / Q000235:genetics* / Q000276:immunology; D044465:White People / Q000235:genetics*; D055815:Young Adult; D000099173:Natural Resistance-associated Macrophage Protein 1
D027682:Cation Transport Proteins; D052247:Nitric Oxide Synthase Type II; D051195:Toll-Like Receptor 2; D000099173:Natural Resistance-associated Macrophage Protein 1; C495342:TLR2 protein, human; C496319:NOS2 protein, human