Association of SLC11A1 with tuberculosis and interactions with NOS2A and TLR2 in African-Americans and Caucasians - PubMed (original) (raw)

Multicenter Study

. 2009 Sep;13(9):1068-76.

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Multicenter Study

Association of SLC11A1 with tuberculosis and interactions with NOS2A and TLR2 in African-Americans and Caucasians

D R Velez et al. Int J Tuberc Lung Dis. 2009 Sep.

Abstract

Setting: 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.

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Figures

Figure 1

Figure 1

SLC11A1 gene map with SNPs analyzed. 15 exons are labeled on the gene map of SLC11A1; untranslated regions are labeled in white and exons in black. The map is oriented 5′ to 3′. SNPs are indicated by vertical lines with SNP ’rs’ number and alternative published nomenclature. Bp = base-pair; SNP = single nucleotide polymorphisms.

Figure 2

Figure 2

LD plots for SLC11A1 unrelated founder controls. LD plots were generated in Haploview and are presented for: A) African-American controls D′; B) African-American controls _r_2; C) Caucasian controls D′; D) Caucasian controls _r_2. Within each triangle is presented the pair-wise correlation coefficient (_r_2) or standardized coefficient of LD (D′). Standard color coding was used for the Haploview LD plots using the confidence bounds color scheme, for D′ LD plots: white = strong evidence of recombination; light grey = uninformative; dark grey = strong evidence of LD; for _r_2 LD plots white (_r_2 = 0), shades of grey (0 < _r_2 < 1), black (_r_2 = 1). Black squares without numbers indicate complete LD (_r_2 = 1.00 or D′ = 1.00). 5′(GT)n repeat was coded with allele 207 coded as one allele and alleles 195, 107, 209 and 211 pooled as another allele. LD = linkage disequilibrium.

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