Gene symbol / Gene name / Chromosomal location / SNP / Location / Base change / Amino acid change
mybbp1a / MYB binding protein 1a / 17p13.3 / rs12603519 / 5'NUTR / G>A
rs3809849 / Exon 1 / G>C / Gln>Glu
rs10852863 / Intron 8 / A>G
rs9907224 / Exon 12 / C>T / Gln>Gln
rs7211078 / Intron 13 / G>T
rs751670 / Exon 20 / T>C / His > His
rs9905742 / Exon 26 / T>A / Met>Leu
rs1045845 / 3'NUTR / C>G
sp110 / SP110 nuclear body protein / 2q37.1 / rs11679983 / Intron 1 / C>T
rs11556887 / Exon 4 / C>T / Ala>Val
rs9061 / Exon 5 / C>T / Glu>Lys
rs1365776 / Exon 8 / A>G / Gly>Arg
rs3948464 / Exon 11 / G>A / Leu>Ser
rs1135791 / Exon 14 / T>C / Met>Thr
relA / v-rel reticuloendotheliosis viral oncogene homolog A / 11q13 / rs7101916 / 5'NUTR / C>T
rs11820062 / Intron 1 / C>T
rs2306365 / Intron 5 / G>A
rs11227247 / Intron 10 / T>G
rs7119750 / Intron 10 / CT
Supplementary Table 2. Primers used for genotyping in this study
SNP / forward PCR primer (5′-3′) / reverse PCR primer (5′-3′) / extension primer (5′-3′)
MASSARRAY method
rs1045845 / ACGTTGGATGACCAGCCCCAACCCGCTTT / ACGTTGGATGAACCACCTTGATTGCAGCAG / CCCCTGCGTCACCCACT
rs10852863 / ACGTTGGATGTGCCCACTACAGGTTAAATC / ACGTTGGATGTGGACTGTTGCAAGTTCAGG / GTGTACAACAGGAGATTGCC
rs3809849 / ACGTTGGATGTTCGTGTTTCGGTGAGTGTG / ACGTTGGATGACTCTGCGTCGCTTCTCCA / CGTCGCTTCTCCAGGCGACATCGGCT
rs7211078 / ACGTTGGATGACAGAAGACCTAAAGCAGCC / ACGTTGGATGAGGCTCAGTACCCTGATTTC / GCAGCCCCAATAAGAGCA
rs751670 / ACGTTGGATGACCCAAGTCGTGGCAGTAG / ACGTTGGATGAATGTTCTGACCAGCTCTCG / CACCACCCACAGGCA
rs9907224 / ACGTTGGATGGAACTGCACCAGGTGGTAG / ACGTTGGATGTCAGCACGCAGTTCAAGCAG / GTGGTAGGTCCAGGG
rs9905742 / ACGTTGGATGCCTTAGCCTTTGTCCTGTTC / ACGTTGGATGATGGCACACCTGCAGCCAC / TTCCTCTTCTTCCTGCCCA
rs12603519 / ACGTTGGATGGGCCCAGAGTTAAAAGAGCG / ACGTTGGATGAAAGATGGGACGCCGCTAGG / ACTTCCGCTCAGAGCTA
rs11679983 / ACGTTGGATGCTTCCCAAGTACCTCTAGTC / ACGTTGGATGTCCTTCAGTGCCCGCAATAG / CTTCAGTGCCCGCAATAGGCGGCT
rs11556887 / ACGTTGGATGCAGAGACACACCAATCCTAC / ACGTTGGATGTGGGGTATGGAGGGAGCTT / ATGGAGGGAGCTTCCTTCT
rs1365776 / ACGTTGGATGAGATGTATCTGGTCAACTCC / ACGTTGGATGCTTCCTCTTGTACTCTCATC / CCTCTTGTACTCTCATCTTACCTC
rs3948464 / ACGTTGGATGCATGATGAGGGTCCAAAAGG / ACGTTGGATGAGCAGATTCCATCATTAGCC / AAATGTGCCCGAAAGTCCAGAT
rs1135791 / ACGTTGGATGGGAAGGAACGCAAAGAACTG / ACGTTGGATGAATACCTTCAGCAGCTCTCC / CTTCAGCAGCTCTCCTAGGGTC
rs11820062 / ACGTTGGATGAGCTGAATCAGGGCCTGTTG / ACGTTGGATGTCAGTTTCCTCTCTGGAGGG / GGCCTGTTGTACTTTCTTAAGGAAAA
rs2306365 / ACGTTGGATGGGGATATAGGTGCTATCAG / ACGTTGGATGGGACTTGTGTTTCACACACG / cCACACGCACCAGCGGCCCTCCCAG
rs7119750 / ACGTTGGATGTCATGGTGCTCAGGCTCAAT / ACGTTGGATGGGGTAAGAGGAAGGAGATAG / GAGGAAGGAGATAGGGTGTT
rs11227247 / ACGTTGGATGGGGGAACAAAAATCACCTC / ACGTTGGATGTGAAGTGCAGAGCTTGTCAG / ATTAGCAAGATGTGTGTGCC
rs7101916 / ACGTTGGATGAAGGCGCGTCCGTGTGGAG / ACGTTGGATGCCTGCAGTGGAGCATCCTC / CCCCACCCCAGGCCTCAT
SNaPshot method
rs11556887 / CTGATGTGTGTCCCTTCACCA / CCCTTCACAGTCACCTTGAGC / CCCCCCCGTATGGAGGGAGCTTCCTTCT
rs9061 / CTGATGTGTGTCCCTTCACCA / CCCTTCACAGTCACCTTGAGC / CGGGCATCTCTTCTGAGTCTTCTT
rs1135791 / GCTGGCTTCAGTCCAAGAGAA / TCCTAACGGGAGCTCTTCACA / CCCCCCCCCCCCCCCTCAGCAGCTCTCCTAGGGTC
Supplementary Table3. The database for the meta-analysis included5studies onSp110 polymorphisms with human pulmonary tuberculosis. The following items are listed for each study: first author, publication year, country and ethnicity of study subjects, characteristics of cases and controls, and method.
First author (year) / Country(ethnicity) / Characteristics of cases / Characteristics of controls / Method
Babb
(2007) / South Africa
(Mixed race) / Patients had a microbiologically confirmed diagnosis of pulmonary TB and were HIV-negative. / Controls were from a healthy population of the same ethnic and socioeconomic group as cases. They had no history of TB. / SNaPshot
Szeszko(2007) / Russia
(Russian) / Patients’ diagnoses were confirmed by sputum culture of MTB. Those with extra-pulmonary TB and/or HIV were excluded / Controls were local adult blood bank donors with no history of TB. / Taqman analysis method
Cong
(2010) / China
(Chinese) / Patients were sputum smear-positive and confirmed by culture-positive formycobacteria and chest X-ray tuberculosislevy like. Theywere withoutpneumonia, lung cancer, pneumoconiosis withtuberculosissimilarillness, HIV, EBV, orhepatitis. / Controls were from a healthy population without pulmonary tuberculosis, other chronic diseases or low immune function. Their ethnicity was matched to cases’. / PCR-RFLP plus sequencing
Liang
(2011) / China
(Chinese) / Patients were clinically and radiologically diagnosed with pulmonary TB, and sputum smears and cultures confirmed M. tuberculosis infections. Patients were HIV-negative and none presented with other infectious diseases or with immunosuppressive conditions / Controls were blood donors who were clinically normal. They had no history of TB, negative PPD tests, and no evidence of prior TB noted in chest radiographies. There were matched to cases by region, ethnic background, age, and sex. / SNaPshot
Png
(2012) / Indonesia
(Indonesian) / Patients were diagnosed with clinical symptoms, chest X-rays, and sputum smear, and then diagnosis was confirmed by sputum culture of M. tuberculosis. Patients with extra-pulmonary TB, diabetes mellitus, and HIV were excluded / Controls were non-genetically related to patients and lacked evidence of TB or TB-related infiltrates in chest X-rays. They were matched to cases by region of residence, age, sex, and ethnicity. / GoldenGate assay plus Taqman functionally tested assay.
Supplementary Table 4.Genotype frequencies of SNPs within Mybbp1a, SP110, and RelA genes in Chinese population
SNP / Genotypes / Controls(%) / Cases(%) / OR(95% CI)* / P / p-trend†
rs12603519 / GG / 221(52.00) / 381(54.27) / Ref
GA / 164(38.59) / 270(38.46) / 1.01[0.77-1.31] / 0.97 / 0.26095
AA / 40(9.41) / 51(7.26) / 0.84[0.67-1.05] / 0.12
rs3809849 / GG / 301(70.82) / 426(60.68) / Ref
GC / 114(26.82) / 239(34.05) / 1.52[1.15-1.99] / 0.003 / 0.00018
CC / 10(2.36) / 37(5.27) / 1.55[1.08-2.23] / 0.017
rs10852863 / AA / 116(27.29) / 236(33.62) / Ref
AG / 217(51.06) / 341(48.58) / 0.78[0.59-1.03] / 0.078 / 0.01821
GG / 92(21.65) / 125(17.81) / 0.80[0.67-0.95] / 0.013
rs9907224 / CC / 101(23.76) / 184(26.21) / Ref
CT / 216(50.82) / 341(48.58) / 0.86[0.64-1.16] / 0.332 / 0.54521
TT / 108(25.41) / 177(25.21) / 0.94[0.79-1.11] / 0.457
rs7211078 / GG / 98(23.11) / 186(26.50) / Ref
GT / 218(51.42) / 314(44.73) / 0.77[0.57-1.05] / 0.097 / 0.98583
TT / 108(25.47) / 202(28.77) / 0.99[0.84-1.18] / 0.926
rs751670 / TT / 139(32.78) / 246(35.04) / Ref
TC / 216(50.94) / 349(49.72) / 0.91[0.70-1.19] / 0.498 / 0.43202
CC / 69(16.27) / 107(15.24) / 0.93[0.77-1.11] / 0.420
rs9905742 / TT / 396(93.18) / 618(88.03) / Ref
TA / 28(6.59) / 78(11.11) / 1.74[1.11-2.73] / 0.017 / 0.00426
AA / 1(0.23) / 6(0.86) / 1.99[0.69-5.75] / 0.204
rs1045845 / CC / 128(30.12) / 237(33.91) / Ref
CG / 209(49.18) / 338(48.35) / 0.88[0.67-1.16] / 0.371 / 0.11853
GG / 88(20.70) / 124(17.74) / 0.865[0.73-1.03] / 0.105
rs11679983 / GG / 393(92.47) / 661(94.16) / Ref
GA / 31(7.29) / 40(5.70) / 0.77[0.47-1.25] / 0.294 / 0.31658
AA / 1(0.24) / 1(0.14) / 0.75[0.19-2.99] / 0.679
rs11556887 / CC / 368(86.59) / 566(80.63) / Ref
CT / 54(12.71) / 124(17.66) / 1.60[1.12-2.28] / 0.010 / 0.00709
TT / 3(0.71) / 12(1.71) / 1.61[0.85-3.04] / 0.142
rs9061 / CC / 277(65.18) / 397(56.55) / Ref
CT / 139(32.71) / 268(38.18) / 1.39[1.07-1.80] / 0.013 / 8.30E-04
TT / 9(2.11) / 37(5.27) / 1.72[1.18-2.51] / 0.005
rs1365776 / AA / 357(84.00) / 556(79.20) / Ref
AG / 64(15.06) / 132(18.80) / 1.33[0.96-1.85] / 0.090 / 0.03128
GG / 4(0.94) / 14(1.99) / 1.47[0.84-2.59] / 0.176
rs3948464 / GG / 402(94.59) / 629(89.60) / Ref
GA / 22(5.17) / 72(10.26) / 2.05[1.25-3.37] / 0.004 / 0.00325
AA / 1(0.24) / 1(0.14) / 0.80[0.20-3.19] / 0.747
rs1135791 / TT / 281(66.12) / 513(73.08) / Ref
TC / 125(29.41) / 176(25.07) / 0.76[0.58-1.0] / 0.048 / 0.003
CC / 19(4.47) / 13(1.85) / 0.58[0.40-0.83] / 0.003
rs7101916 / CC / 171(40.24) / 290(41.31) / Ref
CT / 200(47.06) / 321(45.73) / 0.96[0.74-1.24] / 0.737 / 0.84424
TT / 54(12.71) / 91(12.96) / 0.98[0.81-1.19] / 0.835
rs11820062 / CC / 166(39.06) / 244(34.76) / Ref
CT / 186(43.76) / 347(49.43) / 1.28[0.98-1.67] / 0.074 / 0.4935
TT / 73(17.18) / 111(15.81) / 1.01 [0.84-1.21] / 0.884
rs2306365 / GG / 160(37.65) / 292(41.60) / Ref
GA / 205(48.23) / 303(43.16) / 0.81[0.63-1.06] / 0.124 / 0.50955
AA / 60(14.12) / 107(15.24) / 0.96[0.79-1.16] / 0.656
rs11227247 / TT / 160(37.65) / 293(41.74) / Ref
TG / 205(48.23) / 302(43.02) / 0.81[0.62-1.05] / 0.113 / 0.48862
GG / 60(14.12) / 107(15.24) / 0.96[0.79-1.15] / 0.644
rs7119750 / CC / 160(37.65) / 292(41.60) / Ref
CT / 206(48.47) / 303(43.16) / 0.81[0.62-1.05] / 0.116 / 0.5449
TT / 59(13.88) / 107(15.24) / 0.97[0.80-1.17] / 0.722
SNP indicates single nucleotide polymorphism; Ref,reference; OR,odds ration; CI, confidence interval
* Adjusted for age and gender
† P values were calculated by the Cochran-Armitage's trend test
Supplementary Table5. Results of meta–analysis for SP110polymorphisms andTB
Contrast / Comparisons(n) / OR(95% CI)* / P–value / Ph / I2
rs1135791
T versus C alleles / 5(7530) / 1.11 [0.89–1.39] / 0.36 / 0.007 / 72%
(T/T+T/C) versus C/C / 5(3765) / 1.19 [0.73–1.92] / 0.48 / 0.09 / 53%
T/T versus (T/C+C/C) / 5(3765) / 1.12 [0.85–1.48] / 0.41 / 0.004 / 74%
rs3948464
G versus A alleles / 5(13612) / 1.13 [0.82–1.55] / 0.46 / 0.005 / 73%
(G/G +A/G) versus A/A / 5(6806) / 0.92 [0.62–1.35] / 0.67 / 0.45 / 0%
G/G versus (A/G+ A/A) / 5(6806) / 1.05 [0.92–1.20] / 0.46 / 0.002 / 76%
rs9061
C versus T alleles / 4(5918) / 1.24 [1.08–1.43] / 0.002 / 0.13 / 47%
(C/C+C/T) versus T/T / 4(2959) / 2.78 [1.16–6.66] / 0.02 / 0.07 / 58%
C/C versus (C/C+T/C) / 4(2959) / 1.18 [1.01–1.38] / 0.04 / 0.16 / 42%
OR (95% CI): odds ratio and 95% confidence interval. Ph: P values for heterogeneity for Q test.
* The fixed model was used whenPh >0.1 and the random model was used when Ph<0.1.
Supplementary Figure1.The SP110 SAND domain structure alteration caused by the residue mutant of T523M at the rs1135791 variant site. The 3D SAND structure with the Thr residue (A) is significantly different with the 3D SAND structure with the Metresidue (B). The 3D structure of 1h5pa is described in (C). The structure is colored according to secondary structures: red, yellow and blue meanα-helix,β-sheet and turn.