Association of Toll-like Receptors 1, 2, 4, 6, 8, 9 and 10 Genes Polymorphisms and Susceptibility to Pulmonary Tuberculosis in Sudanese Patients

Figures & data

Figure 1 PCR-RFLP assay for analyzing the TLR4-rs4986790 A/G polymorphisms in Sudanese pulmonary Tuberculosis patients.

Notes: Lane M shows DNA marker; lanes 1 and 6 show AA genotype; lanes 2, 4, and 7 show GA genotype; lanes 3, 5, and 8 show GG genotype.

Figure 2 PCR-RFLP assay for analyzing theTLR8-rs3764879 G/C polymorphisms in Sudanese pulmonary  Tuberculosis patients.

Notes: Lane M shows DNA marker; lanes 2 and 4 show GG genotype; lanes 3 and 6 show CC genotype; lanes 1, 5, and 7 show CG genotype.

Table 1 Characteristics of the Study Population

		Patients	Controls	p-value
Total number		160	220
Mean age /yrs (range)		26 (11–70)	30 (11–70)	1.0٭
Gender (male/female)		111/49	65/155	0.0041٭٭
Occupation	Governmental employee	22 (13.8)	21 (9.55%)	0.05٭٭
	Workers	63 (39.4%)	44 (20%)	<0.0001٭٭
	Other job	40 (25%)	40 (18.3%)	0.58٭٭
	Jobless	3 (1.8%)	13 (5.9%)	<0.0001٭٭
	Housewife	13 (8.1%)	17 (7.7%)	0.03٭٭
	Student	19 (11.9%)	85 (38.6%)	0.15٭٭
BCG vaccination		112 (70.6%)	212 (96.8%)	0.63٭٭
Definite tuberculosis	Presence of MTB in sputum based on both smear and culture	92 (57.5%)	0 (0%)
	Presence of MTB in sputum specimen only by smear	109 (68.1%)	0 (0%)
	Presence of MTB in sputum specimen only by culture	47 (29.4%)	0 (0%)
Hepatitis C test		Negative	Negative
Hepatitis B Ag test		Negative	Negative
HIV1, 2 test		Negative	Negative
Nasopharyngeal swab for (COVID-19)		Negative	Negative

Notes: *Unpaired t-test, ٭٭Fisher exact test.

Table 2 PCR Primers and Restriction Enzymes for genotyping the Different Single Nucleotide Polymorphisms

Gene(s)	Rs Number	Primer Sequence(s) (5’→-3’)	Chromosome Position	Gene Location	Restriction Enzymes	Reference
TLR 1
T/C	rs5743604	F: GAAGAGCAGTCCCAATACCACCAT	chr4:38801285	Intron 3	BsI I	[53,54,58,67]
		R: GGCCCCAAGCTTCCCAAAATTA
C/G	rs5743611	F: GCATCTTCCATTTTGCCATTATCTTC	chr4:38798593	Exon 4	Alu I	[53,54,58,67]
		R: CCAATTCCTGGTTGAATTTGAAAACA
G/T	rs5743618	F: TCCTCATGACTCTTTTCTGC	chr4:38797027	Promoter	Hind III	[53,54,58,67]
		R: GAGGCTTGTCCCTTGCTCCAC
A/G	rs76600635	F: GCATCTTCCATTTTGCCATTATCTTC	chr4: 38800323	Intron	BsI I	[53,54,58,67]
		R: CCAATTCCTGGTTGAATTTGAAAACA
A/G	rs5743551	F: CCGAGATGTTCCCAGCACAG	chr4: 38806033	Promoter	Hind III	[53,54,58,67]
		R :CTGCTTTGCTTGTGCCTCTT
C/T	rs5743557	F:ACGTTGGATGGAGTGTGCTTCAGCAAAAC	chr4:38806827	Near-gene-5	BsI I	[53,54,58,67]
		R:ACGTTGGATGTCTTGCCTTTTCATCCATCC
A/G	rs5743565	F: ACGTTGGATGAGCTGAACAGCAGCATTGCC	chr4:38805983	Exon 2	Hph I	[53,54,58,67]
		R: ACGTTGGATGTTCTCTTCACCTAATCCCGC
C/G	rs5743566	F: ACGTTGGATGAAGGACTAGCTAGTGGGAAG	chr4:38805942	Exon 2	Mbo II	[53,54,58,67]
		R: ACGTTGGATGAGTTACTCCCGGAGGCAATG
A/G	rs5743580	F:ACGTTGGATGAACATCCAGAGTGACTCAGC	chr4:38804405	Intron	Hpy188 III	[53,54,58,67]
		R:ACGTTGGATGTGGCTATGGTAAGCTTCTC
C/T	rs5743594	F:ACGTTGGATGGCTACTCACACAAGGAGCAA	chr4:38802751	Intron	BsI I	[53,54,58,67]
		R:ACGTTGGATGGGGTTAGGATTTCAACATAAG
G/A	rs4833095	F:ACGTTGGATGCTGGAGGATCCTAATGAAAG	chr4:38799710	Exon 4	Bc lI	[53,54,58,67]
		R:ACGTTGGATGCCTAAGTATTCTGGCGAAAC
T/C	rs5743595	F:ACGTTGGATGGGAAATTTCCGGGTCTTTCA	chr4:38802644	Intron	Mly I	[53,54,58,67]
		R:ACGTTGGATGGCAAGGAAGATGATGCAGAC
C/T	rs5743596	F:ACGTTGGATGTGCTCAGGGTCTTCATGAAC	chr4:38802528	Exon 3	Hph I	[53,54,58,67]
		R:ACGTTGGATGGGTGCCCAATATGCCTTTGT
TLR 2
C/T	rs1816702	F: ACGTTGGATGGTGTGAGCCTTACTAAAGGT	chr4:154609523	Intron	BseL I	[53,54,58,67]
		R: ACGTTGGATGCTTTGATTCCTCTAGCGCTG
C/A	rs5743704	F: ACGTTGGATGTGCATCATAGCAGATGTTCC	chr4:154625951	Exon 3	Aci I	[53,54,58,67]
		R: ACGTTGGATGTGAAAATGATGTGGGCCTG
G/A	rs5743708	F:ACGTTGGATGCCAGGTAGGTCTTGGTGTTC	chr4:154626317	Exon 3	Msp I	[53,54,58,67]
		R:ACGTTGGATGTTCTTCTGGAGCCCATTGAG
T/C	rs7656411	F:ACGTTGGATGCCTTTAAATTACTGTGTATC	chr4:154627655	Near gene-3	BspL I	[53,54,58,67]
		R:ACGTTGGATGGTACATGTGAGCTAAATAG
C/T	rs11938228	F:ACGTTGGATGTAGGGACATGCCCATATAGG	chr4:154621946	Near-gene-5	BsaA I	[53,54,58,67]
		R:ACGTTGGATGTAGTGTGTTGCTGGTATAGG
G/A	rs893629	F:ACGTTGGATGACATCACCTGAAACACACCG	chr4:154604968	Near-gene-5	Pst I	[53,54,58,67]
		R:ACGTTGGATGGATTCATGAGCCTGAGTTCG
A/G	rs1898830	F:ACGTTGGATGGATCCCCTATTTTCTAGCAC	chr4:154608453	Intron	EcoRV	[53,54,58,67]
		R: ACGTTGGATGAAAACTGGAAAAGGAATAG
C/T	rs121917864	F:CACGTGAGTCTGAGTTTC	chr4:154626088	Exon 3	Msp I	[53,54,58,67]
		R:GTCTGGTTCAAGAAGTCATACCCCAACCCA AGA GAG’
T/A	rs4696480	F : ACGTTGGATGCTCACCATGTGATGCTTTCC	chr4:154607126	Intron	Mwo I	[53,54,58,67]
		R : ACGTTGGATGGGGAAGTCCAAGATTGAAGG
T/C	rs3804099	F:ACGTTGGATGCTGCTTCATATGAAGGATCAG	chr4:154624656	Exon 3	Tai I	[53,54,58,67]
		R : ACGTTGGATGGATCTACAGAGCTATGAGCC
T/C	rs5743699	F :’ATTTGAACTTATCCA GCACACGAAT	chr4:154625291	Exon 3	Msp I	[53,54,58,67]
		R :TCCAGTGTCTTGGGAATGCA
T/C	rs3804100	F : ACGTTGGATGTTGAACTTATCCAGCACACG	chr4:154625409	Exon 3	Neo I	[53,54,58,67]
		R : ACGTTGGATGTTCCAGTGTCTTGGGAATGC
TLR 4
C/T	rs7869402	F : ACGTTGGATGTTTAGGGAGACACAGATGGC	chr9:120478032	Exon 3	BsI I	[53,54,58,67]
		R : ACGTTGGATGACCTTCACACGTAGTTCTCC
G/A	rs1927907	F: ACGTTGGATGTTTTTCAAACAAGAAGTAG	chr9:120472764	Intron	Not I	[53,54,58,67]
		R: ACGTTGGATGGGGTATCCAGTGGATTGAAG
C/T	rs1927911	F: ACGTTGGATGAGACCTTCCTTAGTCATGGC	chr9:120470054	Intron	Sty I	[53,54,58,67]
		R: ACGTTGGATGCATCACTTTGCTCAAGGGTC
T/C	rs1927914	F : ACGTTGGATGGTGCTTGGAGGATATTACAG	chr9:120464725	Near-gene-5	Sph I	[53,54,58,67]
		R : ACGTTGGATGGAACCTGATTTAAAACAGGA
A/G	rs6478317	F:ACGTTGGATGTCTATCCCAAGATCGGTTCC	chr9:120480210	Near-gene-5	BsI I	[53,54,58,67]
		R:ACGTTGGATGAAGAGGCTAGAAGAAGATAG
A/G	rs55912718	F: AATTCACCAAGCCCAGGCAGAG	chr9:120466480	Near-gene-5	BstU I	[53,54,58,67]
		R: GAGGAAGTGAAAGCGGCAACCT
G/A	rs5030719	F: GCTGAGAAACTTGACCTTCCTGGAC	chr9:120475936	Near-gene-5	Not I	[53,54,58,67]
		R: AGAACCTGGAGGGAGTTCAGACAC
C/T	rs10759931	F: ACCTCAGTGGGCTCTGGGGTAG	chr9:120464147	Near-gene-5	Kpn I	[53,54,58,67]
		R: CCCTTCCTCTGAACCACCTCCT:
A/C	rs10759933	F :ACGTTGGATGGGTAATAAAATATCCAATATCG	chr9:120470372	Intron	Hind III	[53,54,58,67]
		R : ACGTTGGATGTGCTCATCTTCTCTGTATCC
T/C	rs2770150	F: ACGTTGGATGCACTCAATCATTTACTGACC	chr9:120463139	Near-gene-5	Not I	[53,54,58,67]
		R: ACGTTGGATGACACATGGTCTGCCTTCTGG
C/T	rs1554973	F: TGAAGCCATGAATCATTAAGCCAATA	chr9:120480812	Intron	Hae III	[53,54,58,67]
		R: TCCAAAAGCCACGCTACTCAAA
C/A	rs11536878	F:ACGTTGGATGTTCTTGACTACCCACCACAG	chr9:120471553	Intron	ApeK I	[53,54,58,67]
		R:ACGTTGGATGGCGACATATAACAGTAGGTG
A/C	rs11536879	F: CCTGTTGGGGTCAGAAGACCTG	chr9:120472211	Intron	Hinf I	[53,54,58,67]
		R:CATTTAATCCAGCAGAATAAGTTTCATCATTT
G/C	rs7873784	F: ACGTTGGATGGCTCTAAAGATCAGCTGTAT	chr9:120478936	Exon 4	BsI I	[53,54,58,67]
		R: ACGTTGGATGGGTACCCTCTTAACAAAATG
G/C	rs11536889	F :GTTTCCTGTTGGGCAATG CT	chr9:120478131	Near-gene-3	Bcc I	[53,54,58,67]
		R :CATTAATTCCAGCACATTGTTTTCTC
A/G	rs4986790	F: TCTTGCTGGAGTATTCCCTATGA	chr9:120475302	exon 4	Nco1	[53,54,58,67]
		R: GCCACAACCTGCTCTTGC
C/T	rs4986791	F:GGTTGCTGTTCTCAAAGTGATTTTGGGAGAA	chr9:120475602	Exon 4	Hinf I	[53,54,58,67]
		R:ACCTGAAGACTGGAGAGTGAGTTAAATGCT
G/A	rs11536897	F: TTCTGCATAAGTGTGTTTATTCAAGCAAA	chr9:120480010	Exon 4	Xho I	[53,54,58,67]
		R: TCCAGAGGATTTAAAGAGCTAAAAAGAGG
C/A	rs11536898	F: TTCTGCATAAGTGTGTTTATTCAAGCAAA	chr9:120480210	Exon 4	Not I	[53,54,58,67]
		R: TCCAGAGGATTTAAAGAGCTAAAAAGAGG
TLR 6
T/C	rs3796508	F: ACGTTGGATGGTTGCAAAAGATATCCTGCC	chr4:38830736	Exon 1	Nla III	[53,54,58,67]
		R: ACGTTGGATGGCAGGGCCTTGAAATCATTG
C/T	rs5743810	F: ACGTTGGATGATTTTTATCAGAACTCACC	chr4:38830350	Exon 1	Ava II	[53,54,58,67]
		R: ACGTTGGATGAGGCATTTCCAAGTCGTTTC
T/C	rs5743831	F: GTTGGCTTGAGCACCCAAAATG	chr4:38827414	Intron	BstN I	[53,54,58,67]
		R: CTTCTGCCTAACCCCGTGTCCT
T/C	rs1039559	F: ACGTTGGATGGCAAGCAGCAGACACATCAA	chr4:38831596	Near-gene-5	Mbo II	[53,54,58,67]
		R: ACGTTGGATGCTCAGCCTTTTTTCTCCCAC
T/C	rs6531670	F: CCACGAGTGCCCACATATTTCAC	chr4:38835022	Intron	BfaI	[53,54,58,67]
		R: CAGTGTCAGTGGCATTTGGGTTC
C/G	rs5743788	F:ACGTTGGATGGACACTGCAAGAGAGTGAAA	chr4:38833207	Promoter	Nco1	[53,54,58,67]
		R:ACGTTGGATGCAAGTCCCTATCATATATGG
C/T	rs5743794	F: TGAGTTGCCTTTGCTCGTTTGTC	chr4:38832727	Intron	Hind III	[53,54,58,67]
		R: AGCCAGATAACTGACACCACCTAACA
TLR 8
G/A	rs4830805	F: ACGTTGGATGAAGGGAACGTGGAAAATCCG	chrX:12927759	Intron	Kpn I	[53,54,58,67]
		R: ACGTTGGATGATCAGCAGAGACCTGATAGC
C/T	rs4830808	F: ACGTTGGATGGGTAAATGGGTCTCCATTTAG	chrX:12932334	Intron	Apo I	[53,54,58,67]
		R: ACGTTGGATGTCCCACTGGAATTGTTTAGG
C/A	rs3747414	F: ACGTTGGATGGGTCTTAGTTTCAAGTGCGG	chrX:12939412	Exon 2	Hind III	[53,54,58,67]
		R: ACGTTGGATGAGTCAGTAGTCTGAAGCACC
A/G	rs3761624	F: ACGTTGGATGTTGGTTTTCTCCCACTCCTG	chrX:12923681	Near-gene-5	Nco1	[53,54,58,67]
		R: ACGTTGGATGCCCTGGCCACAAGAATAAAG
C/T	rs1548731	F: ACGTTGGATGACCCAAAGAAGTCCATGAGG	chrX:12927947	Intron	Bst7 II	[53,54,58,67]
		R: ACGTTGGATGGAGTGACCTTGAAAACATTC
A/T	rs2109134	F: ACGTTGGATGCCCAGATGAACTCAGAGATG	chrX:12927186	Intron	Mae I	[53,54,58,67]
		R: ACGTTGGATGAAGTGCATCATAGTGTCGCC
A/G	rs3788935	F: ACGTTGGATGGTCTAGTATCTATGTCAAGC	chrX:12922659	Near-gene-5	Msp I	[53,53,58,67]
		R: ACGTTGGATGGTGTGGAGAAAACTGAAGGC
G/A	rs1013150	F: ACGTTGGATGATCACTCAGGGCAGTGTAAG	chrX:12932441	Intron	Nla III	[53,54,58,67]
		R: ACGTTGGATGTTACTAGGAAAAAGATGAG
C/T	rs5744068	F: ACGTTGGATGTCATTTCCTTGCTAGCTGCC	chrX:12935058	Intron	Mwa I	[53,54,58,67]
		R: ACGTTGGATGCCCACAACAAGGAATGCAAG
G/C	rs3764879	F: GTGTGTGTCTGATTTGGGTTG	chrX:12924697	Intron	BfaI	[53,54,58,67]
		R: TTTCTAGGCTCACACCATTTG
C/T	rs5744080	F: ACGTTGGATGGCTGACAAATTTGGAGTTGC	chrX:12937804	Exon 2	Hind III	[53,54,58,67]
		R: ACGTTGGATGGTAGGGAGCTTGGCAGTTTG
A/G	rs3764880	F: ACGTTGGATGGCTAAAGAAATAGAAGTGGC	chrX:12924826	Exon 1	Hpa I	[53,54,58,67]
		R: ACGTTGGATGCTGCTGCAAGTTACGGAATG
C/T	rs17256081	F: ACGTTGGATGGCACTAAAATTTTACAATGC	chrX:12926045	Intron	Alu I	[53,54,58,67]
		R: ACGTTGGATGATGTGTCATTGGCCCAGTTG
C/T	rs5741883	F: ACGTTGGATGAAGCGAGCATCTTTCTCCTG	chrX:12924221	Near-gene-5	Hae III	[53,54,58,67]
		R: ACGTTGGATGACAATGAACACTCATTGAGC
G/C	rs2407992	F: ACGTTGGATGGACTCGCTGGCAAATTAAGG	chrX:12939112	Exon 2	Apo I	[53,54,58,67]
		R: ACGTTGGATGGACACGTCTGGATTTATCCC
G/A	rs178998	F: ACGTTGGATGCCTAAACTGTATGCATTGCC	chrX:12917787	Near-gene-5	Hinc II	[53,54,58,67]
		R” ACGTTGGATGTGGGCCTTCCTGTAGAAGAC
TLR 9
A/G	rs5743836	F: GAGGGTGACATGGGAGCAGAGA	chr3:52260782	Promoter	Mva I	[53,54,58,67]
		R:CTGTGTAGCCCCTGGGCATTCT
G/A	rs164637	F:CCCTGCAGGATGACCTCTCTTT	chr3:52265215	Exon 2	BstNI	[53,54,58,67]
		R:AGGCACCCACCATCTGGATGTA
T/C	rs352139	F:CTGTGGACATCGATATCGGTGT	chr3:52258372	Intron	Hea II	[53,54,58,67]
		R:AAGCTTCGCTGCGGCAGAAACCCTGT
C/T	rs352140	F:TCTAGACATCATGCTGGCCATGACC	chr3:52256697	Intron	BstU I	[53,54,58,67]
		R: CAGAGCCACTCAACAGTGGACT
T/C	rs352143	F: CCCTGCAGGATGACCTCTCTTT	chr3:52264907	Exon 2	Nco1	[53,54,58,67]
		R: AGGCACCCACCATCTGGATGTA
T/C	rs352162	F: CCCTGCAGGATGACCTCTCTTT	chr3:52252969	Intron	Bgl II	[53,54,58,67]
		R: AGGCACCCACCATCTGGATGTA
A/G	rs352165	F: CCCTGCAGGATGACCTCTCTTT	chr3:52242902	Intron	Afl II	[53,54,58,67]
		R: AGGCACCCACCATCTGGATGTA
T/C	rs352167	F: CCCTGCAGGATGACCTCTCTTT	chr3:52238656	Intron	BspTI	[53,54,58,67]
		R: AGGCACCCACCATCTGGATGTA
A/G	rs187084	F:CTGTGGACATCGATATCGGTGT	chr3:52261031	Promoter	Afl II	[53,54,58,67]
		R:AAGCTTCGCTGCGGCAGAAACCCTGT
TLR 10
A/G	rs4129009	F:CCAGAATGAGTGGTGCCATT	chr4:38773268	Exon 4	Vsp I	[53,54,58,67]
		R: GTATGTGGTCCCCAACTTCCC
A/G	rs7694115	F: ACGTTGGATGCTATAGGTTGCCTCAAACAG	chr4:38779094	intron	Ava I	[53,54,58,67]
		R:ACGTTGGATGCAGCAGAAGATTTAGAGTCC
A/C	rs10856839	F: ACGTTGGATGGTTTCTGATGAGTCTCATTG	chr4:38777236	Exon 4	Acc I	[53,54,58,67]
		R: ACGTTGGATGGGGTTTTGAGCTCATCTTC
T/A	rs11466645	F: GATGAGGAAATTGAAGGATCT3′	chr4:38778203	Exon 4	Xba I	[53,54,58,67]
		R: CACTGCTACTTCCCCAGTGC3′
G/A	rs4274855	F: ACGTTGGATGTCCTCTCTGAGAATCCTGAC	chr4:38777471	Exon 3	Xho I	[53,54,58,67]
		R: ACGTTGGATGTTGGCTGAGAAGTCTCCAAG
A/C	rs11096955	F:ACGTTGGATGTGAGAGTTTTCAAGTGAGGC	chr4:38776107	Exon 4	Alu I	[53,54,58,67]
		R:ACGTTGGATGCCAATAATATCTTAACAGACG
G/T	rs11096956	F:ACGTTGGATGCCTGACAATATCAAATGCAC	chr4:38776180	exon 4	Pst I	[53,54,58,67]
		R:ACGTTGGATGAATATTGGAATTTCGTAGG
A/C	rs11096957	F: ACGTTGGATGTAAGCAATAGAACCGATGTC	chr4:38776491	Exon 4	Hind III	[53,54,58,67]
		R: ACGTTGGATGGGCAAAAGCCAATTTGTAAG
G/A	rs7698870	F: ACGTTGGATGTACCACGGGAATGAACAGAG	chr4:38781459	Intron	Nco1	[53,54,58,67]
		R: ACGTTGGATGGATCTCTTCTGAATGACCTC
T/C	rs10776483	F: ACGTTGGATGATGGAATGGGTTCCAGTAAG	chr4:38775040	Exon 4	Hae III	[53,54,58,67]
		R: ACGTTGGATGTGAATTCTACTTTGCCCACC

Table 3 Genotype Distributions and Hardy Weinberg Equilibrium in Sudanese Tuberculosis Patients and Healthy Controls

Genotyp	Tuberculosis Patients N=160(%)	HWE of Patient Population*	Control N=220(%)	HWE of Control Population*
TLR 1 rs5743604
TT	65(40.62)	<0.01	70(31.82)	<0.01
TC	22(13.75)		52(23.63)
CC	73(45.63)		98(44.55)
TLR 1- rs5743611
CC	122(76.25)	<0.01	193(87.72)	<0.01
CG	26(16.25)		19(8.64)
GG	12(7.5)		8(3.64)
TLR 1- rs5743618
GG	148(92.5)	<0.01	201(91,36)	<0.01
GT	8(5.00)		17(7.73)
TT	4(2.5)		2(0.91)
TLR 1 rs76600635
AA	152(95.00)	<0.01	190(86.36)	<0.01
AG	7(4.38)		30(13.64)
GG	1(0.62)		0(0.00)
TLR 1- rs5743551
AA	130(81.25)	<0.01	197(89.55)	<0.01
AG	15(9.37)		18(8.18)
GG	15(9.37)		5(2.27)
TLR 1- rs5743557
CC	60(37.5)		84(38.18)
CT	71(44.38)	<0.01	70(31.82)	<0.01
TT	29(18.12)		66(30.00)
TLR 1- rs5743565
AA	120(75.00)		116(52.73)
AG	26(16.25)	<0.01	65(29.54)	<0.01
GG	14(8.75)		39(17.73)
TLR 1- rs5743566
CC	135(84.38)	<0.01	218(99.09)	<0.01
CG	8(5.00)		2(0.91)
GG	17(10.62)		0(0.00)
TLR 1- rs5743580
AA	79(49.38)	<0.01	81(36.82)	<0.01
AG	39(24.37)		44(20.00)
GG	42(26.25)		95(43.18)
TLR 1- rs5743594
CC	70(43.75)	<0.01	76(34.55)	<0.01
CT	22(14.37)		47(21.36)
TT	68(42.5)		97(44.09)
TLR 1- rs4833095
GG	128(80.00)	<0.01	198(90.00)	<0.01
GA	22(13.75)		18(8.18)
AA	10(6.25)		4(1.82)
TLR 1- rs5743595
TT	122(76.25)	<0.01	212(96,36)	<0.01
TC	10(6.25)		8(3.64)
CC	28(17.5)		0(0.00)
TLR 1- rs5743596
CC	75(46.87)	<0.01	72(32.72)	<0.01
CT	22(13.75)		50(22.73)
TT	63(39.38)		98(44.55)
TLR 2- rs1816702
CC	124(77.5)	<0.01	190(86.36)	<0.01
CT	24(15.0)		22(10.00)
TT	12(7.5)		8(3.64)
TLR 2- rs5743704
CC	144(90.0)		212(96,36)
CA	12(7.5)	<0.01	8(3.64)	<0.01
AA	4(2.5)		0(0.00)
TLR 2- rs5743708
GG	154(96.25)	<0.01	197(89.55)	<0.01
GA	4(2.5)		23(10.45)
AA	2(1.25)		0(0.00)
TLR 2- rs7656411
TT	128(80.00)	<0.01	200(90.91)	<0.01
TC	16 (10.00)		20(9.09)
CC	16(10.00)		0(0.00)
TLR 2- rs11938228
CC	56(35.00)	<0.01	75(34.09)	<0.01
CT	75(46.88)		78(35.45)
TT	29(18.12)		67(30.45)
TLR 2- rs893629
GG	118(73.75)	<0.01	104(47.27)	<0.01
GA	26(16.25)		70(31.82)
AA	16(10.00)		46(20.91)
TLR 2- rs1898830
AA	150(93.75)		216(98.18)
AG	3(1.88)	<0.01	4(1.82)	<0.01
GG	7(4.37)		0(0.00)
TLR 2- rs121917864
CC	74(46.25)	<0.01	76(34.55)	<0.01
CT	46(28.75)		47(21.36)
TT	40(25.0)		97(44.09)
TLR 2- rs4696480
TT	68(42.50)	<0.01	75(34.09)	<0.01
TA	26(16.25)		47(21.36)
AA	66(41.25)		98(44.55)
TLR 2- rs3804099
TT	124(77.5)	<0.01	194(88.18)	<0.01
TC	24(15.0)		20(9.09)
CC	12(7.5)		6(2.73)
TLR 2- rs5743699
TT	144(90.0)	<0.01	216(98.18)	<0.01
TC	10(6.25)		4(1.82)
CC	6(3.75)		0(0.00)
TLR 2- rs3804100
TT	66(41.25)	<0.01	80(36.36)	<0.01
TC	26(16.25)		48(21.82)
CC	68(42.5)		92(41.82)
TLR 4 - rs7869402
CC	128(80.00)	<0.01	190(86.36)	<0.01
CT	22(13.75)		22(10.00)
TT	10(6.25)		8(3.64)
TLR 4 - rs1927907
GG	144(90.00)	<0.01	210(95,45)	<0.01
GA	12(7.5)		10(4.55)
AA	4(2.5)		0(0.00)
TLR 4 - rs1927911
CC	70(43.75)		74(33.63)
CT	22(13.75)	<0.01	48(21.82)	<0.01
TT	68(42.5)		98(44.55)
TLR 4 - rs1927914
TT	126(78.75)	<0.01	188(85.45)	<0.01
TC	22(13.75)		20(9.09)
CC	12(7.5)		12(5.45)
TLR 4 - rs6478317
AA	140(87.5)	<0.01	182(82.73)	<0.01
AG	16(10.0)		38(17.27)
GG	4(2.5)		0(0.00)
TLR 4 - rs55912718
AA	152(95.0)	<0.01	190(86.36)	<0.01
AG	4(2.5)		30(13.64)
GG	4(2.5)		0(0.00)
TLR 4 - rs5030719
GG	124(77.5)	<0.01	202(91.82)	<0.01
GA	20 (12.5)		18(8.18)
AA	16(10.0)		0(0.00)
TLR 4 - rs10759931
CC	60(37.5)	<0.01	70(31.82)	<0.01
CT	73(45.63)		78(35.45)
TT	27(16.87)		72(32.73)
TLR 4 - rs10759933
AA	122(76.25)	<0.01	108(49.09)	<0.01
AC	24(15.00)		68(30.91)
CC	14(8.75)		44(20.00)
TLR 4 - rs2770150
TT	150(93.75)	<0.01	216(98.18)	<0.01
TC	3(1.88)		4(1.82)
CC	7(4.37)		0(0.00)
TLR 4 – rs1554973
CC	74(46.25)	<0.01	76(34.55)	<0.01
CT	46(28.75)		48(21.82)
TT	40(25.00)		96(43.63)
TLR 4 - rs11536878
CC	72(43.13)	<0.01	74(33.63)	<0.01
CA	40(14.37)		48(21.82)
AA	48(42.5)		98(44.55)
TLR 4 - rs11536879
AA	120(75.00)	<0.01	192(87.27)	<0.01
AC	28(17.5)		22(10.00)
CC	12(7.5)		6(2.73)
TLR 4 - rs7873784
GG	144(90.00)	<0.01	212(96,36)	<0.01
GC	12(7.5)		8(3.64)
CC	4(2.5)		0(0.00)
TLR 4 - rs11536889
GG	70(43.75)	<0.01	74(33.63)	<0.01
GC	22(13.75)		48(21.82)
CC	68(42.5)		98(44.55)
TLR 4 - rs4986790
AA	128(80.00)	<0.01	194(88.18)	<0.01
AG	20(12.5)		18(8.18)
GG	12(7.5)		8(3.64)
TLR 4 - rs4986791
CC	70(43.75)	<0.01	90(40.91)	<0.01
CT	22(13.75)		44(20.00)
TT	68(42.5)		86(39.09)
TLR 4 - rs11536897
GG	124(77.5)	<0.01	192(87.27)	<0.01
GA	20(12.5)		24(10.91)
AA	16(10.0)		4(1.82)
TLR 4 - rs11536898
CC	152(95.00)	<0.01	216(98,18)	<0.01
CA	6(3.75)		4(1.82)
AA	2(1.25)		0(0.00)
TLR 6- rs3796508
TT	146(91.25)	<0.01	202(91.82)	<0.01
TC	10(6.25)		16(7.27)
CC	4(2.5)		2(0.91)
TLR 6- rs5743810
CC	130(81.25)	<0.01	203(92.73)	<0.01
CT	15 (9.37)		15(7.27)
TT	15(9.37)		2(0.91)
TLR 6- rs5743831
TT	60(37.5)	<0.01	70(31.82)	<0.01
TC	73(45.62)		78(35.45)
CC	27(16.88)		72(32.73)
TLR 6- rs1039559
TT	70(43.75)	<0.01	100(45.45)	<0.01
TC	24(15.00)		48(21.82)
CC	66(41.25)		72(32.73)
TLR 6- rs6531670
TT	74(46.25)	<0.01	102(46.36)	<0.01
TC	22(13.75)		40(18.18)
CC	64(40.00)		78(35.45)
TLR 6- rs5743788
CC	128(80.00)	<0.01	186(84.55)	<0.01
CG	20(12.5)		30(13.63)
GG	12(7.5)		4(1.82)
TLR 6- rs5743794
CC	122(76.25)	<0.01	216(98,18)	<0.01
CT	36(22.50)		4(1.82)
TT	2(1.25)		0(0.00)
TLR 8- rs4830805
GG	75(46.88)	<0.01	88(40.00)	<0.01
GA	22(13.75)		42(19.09)
AA	63(39.37)		90(40.91)
TLR 8- rs4830808
CC	128(80.00)	<0.01	194(88.18)	<0.01
CT	22(13.75)		22(10.00)
TT	10(6.25)		4(1.82)
TLR 8- rs3747414
GG	150(93.75)	<0.01	216(98,18)	<0.01
GT	8(5.00)		4(1.82)
TT	2(1.25)		0(0.00)
TLR 8- rs3761624
CC	146(91.25)	<0.01	200(90.91)	<0.01
CA	9(5.63)		20(9.09)
AA	5(3.12)		0(0.00)
TLR 8- rs1548731
CC	131(81.88)	<0.01	204(92.73)	<0.01
CT	14 (8.75)		16(7.27)
TT	15(9.37)		0(0.00)
TLR 8- rs2109134
AA	58(36.25)	<0.01	75(34.09)	<0.01
AT	73(45.63)		78(35.45)
TT	29(18.12)		67(30.45)
TLR 8- rs3788935
AA	69(43.13)	<0.01	75(34.09)	<0.01
AG	23(14.37)		47(21.36)
GG	68(42.5)		98(44.55)
TLR 8- rs1013150
GG	130(81.25)		204(92.73)
AG	14 (8.75)	<0.01	16(7.27)	<0.01
AA	16(10.0)		0(0.00)
TLR 8- rs5744068
CC	52(32.5)	<0.01	80(36.36)	<0.01
CT	76(47.5)		73(33.18)
TT	32(20.0)		67(30.45)
TLR 8- rs3764879
GG	80(50.0)	<0.01	70(31.82)	<0.01
GC	40(25.0)		60(27.27)
CC	40(25.0)		90(40.91)
TLR 8- rs5744080
CC	70(43.75)	<0.01	83(37.73)	<0.01
CT	20(12.5)		47(21.36)
TT	70(43.75)		90(40.91)
TLR 8- rs3764880
AA	155(96.87)	<0.01	218(99.09)	<0.01
AG	1(0.63)		2(0.91)
GG	4(2.5)		0(0.00)
TLR 8- rs17256081
CC	86(53.75)	<0.01	210(95.45)	<0.01
CT	52(32.5)		10(4.55)
TT	22(13.75)		0(0.00)
TLR 8- rs5741883
CC	75(46.88)	<0.01	216(98.2)	<0.01
CT	8(5.00)		4(1.8)
TT	77(48.12)		0(0.0)
TLR 8- rs2407992
GG	136(85.00)	<0.01	170(77.27)	<0.01
GC	10(6.25)		40(18.18)
CC	14(8.75)		10(4.55)
TLR 8- rs178998
GG	98(61.25)		198(90.00)
GA	22(13.75)	<0.01	20(9.09)	<0.01
AA	40(25.00)		2(0.91)
TLR 9- rs5743836
AA	69(43.13)	<0.01	75(34.09)	<0.01
AG	23(14.37)		47(21.36)
GG	68(42.5)		98(44.55)
TLR 9- rs164637
GG	126(78.75)	<0.01	192(87.27)	<0.01
GA	22(13.75)		20(9.09)
AA	12(7.5)		8(3.64)
TLR 9- rs352139
TT	146(91.25)	<0.01	213(96,82)	<0.01
TC	10(6.25)		7(3.18)
CC	4(2.5)		0(0.00)
TLR 9- rs352140
CC	155(96.88)	<0.01	197(89.55)	<0.01
CT	4(2.5)		23(10.45)
TT	1(0.62)		0(0.00)
TLR 9- rs352143
TT	129(80.63)	<0.01	202(91.82)	<0.01
TC	15 (9.37)		18(8.18)
CC	16(10.0)		0(0.00)
TLR 9- rs352162
TT	58(36.25)	<0.01	75(34.09)	<0.01
TC	73(45.63)		78(35.45)
CC	29(18.12)		67(30.45)
TLR 9- rs352165
AA	120(75.00)		106(48.18)
AG	26(16.25)	<0.01	70(31.82)	<0.01
GG	14(8.75)		44(20.00)
TLR 9- rs352167
TT	152(95.00)	<0.01	216(98.18)	<0.01
TC	1(0.63)		4(1.82)
CC	7(4.37)		0(0.00)
TLR 9- rs187084
AA	76(47.5)	<0.01	74(33.64)	<0.01
AG	44(27.5)		49(22.27)
GG	40(25.0)		97(44.09)
TLR 10- rs4129009
AA	75(46.88)	<0.01	88(40.00)	<0.01
AG	22(13.75)		42(19.09)
GG	63(39.37)		90(40.91)
TLR 10- rs7694115
AA	128(80.00)	<0.01	194(88.18)	<0.01
AG	22(13.75)		22(10.00)
GG	10(6.25)		4(1.82)
TLR 10- rs10856839
AA	150(93.75)	<0.01	216(98,18)	<0.01
AC	8(5.00)		4(1.82)
CC	2(1.25)		0(0.00)
TLR 10- rs11466645
TT	146(91.25)	<0.01	200(90.91)	<0.01
TA	9(5.63)		20(9.09)
AA	5(3.12)		0(0.00)
TLR 10- rs4274855
GG	131(81.88)	<0.01	204(92.73)	<0.01
GA	14 (8.75)		16(7.27)
AA	15(9.37)		0(0.00)
TLR 10- rs11096955
AA	58(36.25)	<0.01	75(34.09)	<0.01
AC	73(45.63)		78(35.45)
CC	29(18.12)		67(30.45)
TLR 10- rs11096956
GG	69(43.13)	<0.01	75(34.09)	<0.01
GT	23(14.37)		47(21.36)
TT	68(42.5)		98(44.55)
TLR 10- rs11096957
AA	130(81.25)	<0.01	204(92.73)	<0.01
AC	14 (8.75)		16(7.27)
CC	16(10.0)		0(0.00)
TLR 10- rs7698870
GG	52(32.5)	<0.01	80(36.36)	<0.01
GA	76(47.5)		73(33.18)
AA	32(20.0)		67(30.45)
TLR 10- rs10776483
TT	80(50.0)	<0.01	70(31.82)	<0.01
TC	40(25.0)		60(27.27)
CC	40(25.0)		90(40.91)

Note: *HWE was performed with Pearson’s χ² test.

Table 4 Allele Frequencies of Tuberculosis Patients in Comparison to a Matching Healthy Control Population

Genotype	Tuberculosis Patients N=160(%)	Control N=220(%)	P-value for Association*	OR (95% CI)
TLR 1- rs5743604 T/C
T-allele	152	192	0.352	1.03 (0.79–1.63)
C-allele	168	239
TLR 1- rs5743611C/G
C-allele	270	405	0.674	1.09 (0.75–1.45)
G-allele	50	35
TLR 1- rs5743618G/T
G-allele	304	419	0.456	1.18 (0.75–1.74)
T-allele	24	21
TLR 1- rs76600635A/G
A-allele	311	410	0.182	1.20 (0.80–1.26)
G-allele	9	30
TLR 1- rs5743551A/G
A-allele	275	412	0.472	1.26 (0.66–2.24)
G-allele	45	28
TLR 1- rs5743557C/T
C-allele	191	238	<0.0001	1.39 (0.77–2.40)
T-allele	129	202
TLR 1- rs5743565A/G
A-allele	266	297	0.672	1.33 (0.67–2.17)
G-allele	54	143
TLR 1- rs5743566C/G
C-allele	278	438	0.344	1.22 (0.85–1.45)
G-allele	42	2
TLR 1- rs5743580A/G
A-allele	197	206	0.455	1.15 (0.76–1.76)
G-allele	123	234
TLR 1- rs5743594C/T
C-allele	162	199	0.621	1.23 (0.78–1.65)
T-allele	158	241
TLR 1- rs4833095 G/A
G-allele	278	414	<0.0001	1.17 (0.77–1.89)
A-allele	42	26
TLR 1- rs5743595 T/C
T-allele	254	432	0.662	1.05 (0.64–1.78)
C-allele	66	8
TLR 1- rs5743596 C/T
C-allele	172	194	<0.0001	1.00 (0.54–1.45)
T-allele	148	246
TLR 2- rs1816702C/T
C-allele	272	402	0.705	1.57 (1.40–2.25)
T-allele	48	38
TLR 2- rs5743704C/A
C-allele	300	432	<0.0001	1.15 (0.75–1.45)
A-allele	20	8
TLR 2- rs5743708 G/A
G-allele	312	417	<0.0001	1.23 (0.95–1.45)
A-allele	8	23
TLR 2- rs7656411 T/C
T-allele	272	420	0.234	1.97 (0.75–2.12)
C-allele	48	20
TLR 2- rs11938228 C/T
C-allele	187	228	0.648	1.93 (0.54–2.15)
T-allele	133	212
TLR 2- rs893629 G/A
G-allele	262	278	0.870	1.95 (0.65–2.19)
A-allele	58	162
TLR 2- rs1898830 A/G
A-allele	303	436	0.239	1.93 (0.58–2.98)
G-allele	17	4
TLR 2- rs121917864 C/T
C-allele	194	199	0.544	1.99 (0.68–2.45)
T-allele	126	241
TLR 2- rs4696480 T/A
T-allele	162	197	0.635	1.12 (0.76–1.45)
A-allele	158	243
TLR 2- rs3804099 T/C
T-allele	272	408	<0.0001	1.19 (0.87–1.57)
C-allele	48	32
TLR 2- rs5743699 T/C
T-allele	298	436	0.681	1.01 (0.90–1.35)
C-allele	22	4
TLR 2- rs3804100 T/C
T-allele	158	208	0.569	1.08 (0.65–1.19)
C-allele	162	232
TLR 4 - rs7869402 C/T
C-allele	278	402	0.528	1.90 (0.60–2.35)
T-allele	42	38
TLR 4 - rs1927907 G/A
G-allele	300	430	0.536	1.84 (0.63–2.12)
A-allele	20	10
TLR 4 - rs1927911 C/T
C-allele	162	196	0.255	1.02 (0.65–1.61)
T-allele	158	244
TLR 4 - rs1927914 T/C
T-allele	274	396	0.225	1.98 (0.77–2.25)
C-allele	46	44
TLR 4 - rs6478317 A/G
A-allele	296	402	0.564	1.18 (1.03–1.33)
G-allele	24	38
TLR 4 - rs55912718 A/G
A-allele	308	410	0.587	1.06 (0.76–1.26)
G-allele	12	30
TLR 4 - rs5030719 G/A
G-allele	268	422	0.434	1.36 (0.72–2.55)
A-allele	52	18
TLR 4 - rs10759931 C/T
C-allele	193	218	0.737	1.96 (0.76–2.23)
T-allele	127	222
TLR 4 - rs10759933 A/C
A-allele	268	284	0.767	1.90 (0.77–2.19)
C-allele	52	156
TLR 4 - rs2770150 T/C
T-allele	303	436	0.307	1.12 (0.94–1.28)
C-allele	17	4
TLR 4 – rs1554973 C/T
C-allele	194	200	0.482	1.20 (0.99–2.23)
T-allele	126	240
TLR 4 - rs11536878 C/A
C-allele	184	196	0.881	1.58 (0.35–2.04)
A-allele	136	244
TLR 4 - rs11536879 A/C
A-allele	268	402	0.633	1.11 (0.95–2.25)
C-allele	52	34
TLR 4 - rs7873784 G/C
G-allele	300	432	0.566	1.14 (0.93–1.32)
C-allele	20	8
TLR 4 - rs11536889 G/C
G-allele	162	196	0.235	1.12 (0.60–2.07)
C-allele	158	244
TLR 4 - rs4986790 A/G
A-allele	276	406	<0.0001	1.31 (0.65–2.66)
G-allele	44	34
TLR 4 - rs4986791 C/T
C-allele	162	224	<0.0001	1.32 (0.88–1.187)
T-allele	158	216
TLR 4 - rs11536897 G/A
G-allele	268	408	0.663	1.40 (0.86–2.23)
A-allele	52	32
TLR 4 - rs11536898 C/A
C-allele	310	436	0.773	1.37 (0.83–2.26)
A-allele	10	4
TLR 6- rs3796508 T/C
T-allele	302	420	0.235	1.54 (1.05–2.16)
C-allele	18	20
TLR 6- rs5743810 C/T
C-allele	275	421	<0.0001	1.19 (0.85–1.76)
T-allele	45	19
TLR 6- rs5743831 T/C
T-allele	193	218	0.698	1.22 (0.73–2.35)
C-allele	127	222
TLR 6- rs1039559 T/C
T-allele	164	248	0.623	1.11 (0.96–1.50)
C-allele	156	192
TLR 6- rs6531670 T/C
T-allele	170	244	0.690	1.09 (0.96–1.45)
C-allele	150	196
TLR 6- rs5743788 C/G
C-allele	276	402	0.543	1.23 (0.53–243)
G-allele	44	38
TLR 6- rs5743794 C/T
C-allele	280	436	0.598	1.18 (0.95–2.45)
T-allele	40	4
TLR 8- rs4830805 G/A
G-allele	172	218	0.530	1.92 (0.85–4.32)
A-allele	148	222
TLR 8- rs4830808 C/T
C-allele	278	410	0.827	1.08 (0.56–2.09)
T-allele	42	30
TLR 8- rs3747414 G/T
G-allele	308	436	0.517	1.56 (0.93–2.62)
T-allele	12	4
TLR 8- rs3761624 C/A
C-allele	301	420	1.000	1.90 (1.40–2.56)
A-allele	19	20
TLR 8- rs1548731 C/T
C-allele	276	424	0.629	1.07 (0.74–1.55)
T-allele	44	16
TLR 8- rs2109134 A/T
A-allele	189	228	0.299	1.68 (1.07–2.65)
T-allele	131	212
TLR 8- rs3788935 A/G
A-allele	161	197	0.652	1.28 (0.74, 2.22)
G-allele	159	243
TLR 8- rs1013150 G/A
G-allele	274	424	0.851	1.32 (0.74, 2.38)
A-allele	46	16
TLR 8- rs5744068 C/T
C-allele	180	233	0.245	1.98 (1.45–2.60)
T-allele	140	207
TLR 8- rs3764879 G/C
G-allele	200	200	<0.0001	1.81 (1.31–2.44)
C-allele	120	240
TLR 8- rs5744080 C/T
C-allele	160	213	0.540	1.23 (0.67, 2.27)
T-allele	160	227
TLR 8- rs3764880 A/G
A-allele	311	438	<0.0001	1.43 (0.79–2.760)
G-allele	9	2
TLR 8- rs17256081 C/T
C-allele	224	430	1.000	1.10 (0.76, 1.60)
T-allele	96	10
TLR 8- rs5741883 C/T
C-allele	158	436	0.618	1.20 (0.92–1.57)
T-allele	162	4
TLR 8- rs2407992 G/C
G-allele	282	380	0.543	1.26 (0.97–1.65)
C-allele	38	60
TLR 8- rs178998 G/A
G-allele	218	416	0.833	1.15 (0.77, 1.70)
A-allele	102	24
TLR 9- rs5743836 A/G
A-allele	161	197	0.09	1.25 (0.96–1.66)
G-allele	159	243
TLR 9- rs164637 G/A
G-allele	274	404	0.06	(0.90–0.10)0.28
A-allele	46	36
TLR 9- rs352139 T/C
T-allele	302	433	0.26	1.46 (0.79–2.75)
C-allele	18	7
TLR 9- rs352140 C/T
C-allele	314	417	0.34	1.90 (1.40–2.56)
T-allele	6	23
TLR 9- rs352143 T/C
T-allele	273	422	0.20	1.20 (0.92–1.57)
C-allele	47	18
TLR 9- rs352162 T/C
T-allele	189	228	0.25	1.26 (0.97–1.65)
C-allele	131	212
TLR 9- rs352165 A/G
A-allele	266	282	<0.0001	1.91 (1.41–2.57)
G -allele	54	158
TLR 9- rs352167 T/C
T-allele	305	436	<0.0001	1.47 (0.78–2.76)
C-allele	15	4
TLR 9- rs187084 A/G
A-allele	196	197	<0.0001	1.98 (1.45–2.60)
G-allele	124	243
TLR 10- rs4129009 A/G
A-allele	172	218	<0.0001	1.36 (1.01–1.81)
G-allele	148	222
TLR 10- rs7694115 A/G
A-allele	278	410	0.468	1.92 (1.19–3.12)
G-allele	42	30
TLR 10- rs10856839 A/C
A-allele	308	436	0.729	1.94(1.14–3.12)
C-allele	12	4
TLR 10- rs11466645 T/A
T-allele	301	420	0.154	1.13 (0.84–1.45)
A-allele	19	20
TLR 10- rs4274855 G/A
G-allele	276	424	0.370	1.52 (0.86–2.58)
A-allele	44	16
TLR 10- rs11096955 A/C
A-allele	189	228	0.084	1.36 (0.89–2.06)
C-allele	131	212
TLR10- rs11096956 G/T
G-allele	161	197	0.446	1.34 (0.79–2.28)
T-allele	159	243
TLR10- rs11096957 A/C
A-allele	274	424	0.275	1.58 (1.01–2.47)
C-allele	46	16
TLR 10- rs7698870 G/A
G-allele	180	233	0.296	1.35 (0.77–2.38)
A-allele	140	207
TLR10- rs10776483 T/C
T-allele	200	200	0.543	1.47 (0.62–3.56)
C-allele	120	240

Notes: *P-values are calculated with the Fisher exact test. Significant p-value (<0.05) are shown in bold.

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