Single nucleotide polymorphisms in IFN-gamma, TNF-alpha, IL-6, IL-10, and TGF-beta in pulmonary and extrapulmonary tuberculosis in the State of Ceará, northeastern Brazil

Luiz, Roberta dos Santos Silva; Campelo, Thales Alves; Silva, Caroliny Soares; Nogueira, Lucas de Lima; Sancho, Soraya de Oliveira; da Silva, Ana Karolliny Alves; Frota, Cristiane Cunha; Carvalho-Costa, Filipe Anibal

doi:10.1590/0074-02760240147

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Sumário

RESEARCH ARTICLE • Mem. Inst. Oswaldo Cruz 120 • 2025 • https://doi.org/10.1590/0074-02760240147 linkcopy

Single nucleotide polymorphisms in IFN-gamma, TNF-alpha, IL-6, IL-10, and TGF-beta in pulmonary and extrapulmonary tuberculosis in the State of Ceará, northeastern Brazil

Authorship SCIMAGO INSTITUTIONS RANKINGS

Abstract

BACKGROUND Single nucleotide polymorphisms (SNP) in genes encoding cytokines influence tuberculosis (TB) outcomes.

OBJECTIVES To characterise genotypes of the SNPs IFN-gamma +874 T > A, TNF-alpha -308 G > A, IL-6 -174 G > C, IL-10 -1082A > G, TGF-beta codon 10 T > C, and TGF-beta codon 25 G > C in patients with pulmonary (PTB) and extrapulmonary TB (EPTB).

METHODS 82 PTB and 45 EPTB cases were compared, concerning genotype distribution of the mentioned SNPs, characterised via sequence-specific primer polymerase chain reaction (PCR).

FINDINGS Regarding IFN-gamma +874 T > A, AA genotype was the most frequent in both groups, TA was more frequent in PTB and TT in EPTB, with no statistical significance. For SNP TNF-alpha -308 G > A, GG was more frequent in both groups of patients. Regarding the IL-6 -174 G > C polymorphism, GG predominated in both groups, while CG and GG were significantly more frequent in patients with PTB and EPTB, respectively. Concerning IL-10 -1082 A > G, AA predominated in both PTB and EPTB. Concerning TGF-beta codon 10 T > C, CC predominated in PTB while TC predominated in EPTB, but the differences were not statistically significant. Genotype GG of TGF-beta codon 25 G > C predominated among PTB and EPTB patients.

MAIN CONCLUSIONS Except for IL-6, the genotype profile could not differentiate PTB and EPTB. Hence, the studied SNPs are not significantly associated with the extrapulmonary involvement of TB.

Key words:
tuberculosis; single nucleotide polymorphism; cytokines

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[TFN1] ^* Lymph node (n = 18); pleural (n = 13); breast (n = 7); osteoarticular system (n = 3); central nervous system (n = 2); ovary (n = 1); and larynx (n = 1). ^** Assessed with GeneXpert MTB/RIF. PTB: pulmonary tuberculosis; EPTB: extrapulmonary tuberculosis.

	PTB (n = 82)	EPTB (n = 45)^*	p-value
Gender
Male	59 (72%)	19 (42%)	< 0.001
Female	23 (28%)	26 (58%)
Age
Mean age ± standard deviation	38.4 ± 14.8	36.4 ± 15.5	0.708
Age range (years)	15-80	17-70
Proportion with rifampicin-resistant Mycobacterium tuberculosis ^**	59 (72%)	7 (15.6%)	< 0.001

	PTB	EPTB	OR (95% CI)	p-value
IFN-gamma +874 T > A	N = 65	N = 36
AA (low^* )	26 (40%)	15 (41.7%)	0.93 (0.40 - 2.19)	1.000
TA (intermediate^* )	26 (40%)	8 (22.2%)	2.33 (0.92 - 5.90)	0.081
TT (high^* )	13 (20%)	13 (36.1%)	0.44 (0.17 - 1.10)	0.097
Allele A	78 (60%)	38 (52.8%)	1.34 (0.75 - 2.39)	0.373
Allele T	52 (40%)	34 (47.2%)	0.74 (0.41 - 1.33)	0.373
TNF-alpha -308 G > A	N = 68	N = 40
GG (low^** )	53 (77.9%)	32 (80%)	0.88 (0.33 - 2.13)	1.000
AG (high^** )	15 (22.1%)	8 (20%)	1.13 (0.43 - 2.96)	1.000
Allele A	15 (11%)	8 (10%)	1.11 (0.45 - 2.76)	1.000
Allele G	121 (89%)	72 (90%)	0.89 (0.36 - 2.21)	1.000
IL-6 174G > C	N = 73	N = 40
CC (low^*** )	8 (11%)	5 (12.5%)	0.86 (0.26 - 2.83)	0.768
CG (intermediate^*** )	29 (39.7%)	7 (17.5%)	3.10 (1.21 - 7.96)	0.019
GG (high^*** )	36 (49.3%)	28 (70%)	0.41 (0.18 - 0.94)	0.046
Allele C	45 (30.8%)	17 (21.3%)	1.65 (0.87 - 3.13)	0.160
Allele G	101 (69.2%)	63 (78.7%)	0.60 (0.31 - 1.14)	0.160
IL-10 -1082 A > G	N = 29	N = 16
AA	15 (51.7%)	11 (68.8%)	0.48 (0.13 - 1.75)	0.351
AG	10 (34.5%)	2 (12.5%)	3.68 (0.69 - 19.52)	0.164
GG	4 (13.8%)	3 (18.7%)	0.69 (0.13 - 3.57)	0.685
Allele A	40 (69%)	24 (75%)	0.74 (0.27 - 1.96)	0.631
Allele G	18 (31%)	8 (25%)	1.35 (0.50 - 3.57)	0.631
TGF-beta codon 10 (T > C)	N = 70	N = 36
CC	30 (42.8%)	11 (30.6%)	1.70 (0.72 - 3.99)	0.292
TC	21 (30%)	16 (44.4%)	0.53 (0.23 - 1.13)	0.196
TT	19 (27.2%)	9 (25%)	1.11 (0.44 - 2.80)	1.000
Allele C	81 (57.9%)	38 (52.8%)	1.22 (0.69 - 2.17)	0.559
Allele T	59 (42.1%)	34 (47.2%)	0.81 (0.45 - 1.44)	0.559
TGF-beta codon 25 (G > C)	N = 70	N = 36
CC	0 (0%)	4 (11.1%)	Undefined
GC	10 (14.3%)	4 (11.1%)	1.33 (0.38 - 4.59)	0.768
GG	60 (85.7%)	28 (77.8%)	1.71 (0.61 - 4.81)	0.412
Allele C	10 (7.1%)	12 (33.3%)	0.38 (0.15 - 0.93)	0.054
Allele G	130 (92.9%)	60 (66.6%)	2.60 (1.06 - 6.35)	0.054