Impact of Cytokine Genes on TMD and QoL in Construction Workers

As disfunções temporomandibulares (DTM) incluem alterações relacionadas à presença de dor orofacial, limitação da abertura bucal e problemas inflamatórios. Esses problemas inflamatórios estão relacionados às interleucinas, que são mediadores inflamatórios. Assim, a presença de polimorfismos genéticos em genes que codificam interleucinas pode impactar a DTM. Portanto, este estudo transversal teve como objetivo avaliar o impacto de polimorfismos genéticos nos genes que codificam interleucinas na qualidade de vida relacionada à saúde bucal (QVRSB) de indivíduos com DTM. Um total de 230 trabalhadores da construção civil do sexo masculino foram avaliados quanto à presença de DTM com ou sem dor, bem como alterações na articulação temporomandibular (ATM) utilizando os Critérios de Diagnóstico de Pesquisa para Disfunções Temporomandibulares (RDC/TMD). A QVRSB foi avaliada utilizando o Perfil de Impacto à Saúde Bucal (OHIP-14) de 14 itens. O DNA extraído da saliva foi usado para avaliar os polimorfismos genéticos em IL1B (rs1143627 e rs1143629) e IL6 (rs1800795 e rs1800796) usando reação em cadeia da polimerase em tempo real. O teste t de Student ou ANOVA foi usado para análise estatística (alfa = 5%). Uma associação entre OHIP-14 e DTM foi observada (p < 0,05). Os indivíduos heterozigotos AG em rs1143629 apresentaram valores aumentados nos domínios 2 (dor física) e 4 (incapacidade física) em comparação com homozigotos AA (p = 0,035; p = 0,042, respectivamente). Indivíduos homozigotos para o alelo C em rs1800796 demonstraram valores mais altos no domínio 7 (deficiência) em comparação com indivíduos heterozigotos CG e homozigotos GG (p = 0,007). Em conclusão, nosso estudo apoiou a hipótese de que DTM e polimorfismos genéticos associados a distúrbios inflamatórios estão associados à qualidade de vida relacionada à saúde (QVRSB).

Gene	Genetic polymorphism	Position	Type of alteration	Mutant allele	MAF	Genotypes n(%)			H-W p-value
Gene	Genetic polymorphism	Position	Type of alteration	Mutant allele	MAF	Homozygous dominant	Heterozygous	Homozygous recessive
IL1B (Interleukin 1 beta)	rs1143627	Chromosome 2: 112836810 (GRCh38)	Transcript Variant	G/A	0.47	68 (33.3)	85 (41.7)	51 (25.0)	0.021
IL1B (Interleukin 1 beta)	rs1143629	Chromosome 2: 112835941 (GRCh38)	Intron Variant	A/G	0.48	77 (37)	77 (37)	54 (26)	0.0003
IL6 (Interleukin 6)	rs1800795	Chromosome 7:22727026 (GRCh38)	Intron Variant	C/G	0.14	114 (53.0)	78 (36.3)	23 (10.7)	0.089
IL6 (Interleukin 6)	rs1800796	Chromosome 7: 22726627 (GRCh38)	Transcript Variant	C/G	0.31	131 (63.6)	67 (32.5)	8 (3.9)	0.877

	OHIP-14
	Total Scale		Functional limitation		Physical pain		Psychological discomfort
Variables	Mean (SD)	p value	Mean (SD)	p value	Mean (SD)	p value	Mean (SD)	p value
Myofascial Pain
Absence	6.39 (6.11)^a	< 0.001*	0.27 (0.93)^a	0.692	0.91 (1.44)^a	0.028*	1.72 (1.91)^a	0.005*
Pain	12.50 (7.01)^b		0.44 (1.04)^a		1.88 (1.81)^b		3.00 (2.14)^b
Pain with limitation	11.00 (1.41)^ab		-		1.00 (1.41)^ab		4.50 (0.70)^ab
Inflammatory disorder
Absence	6.14 (6.26)	0.001*	0.27 (0.96)	0.723	0.87 (1.45)	0.044*	1.61 (1.91)	0.001*
Presence	9.28 (6.19)	0.001*	0.32 (0.87)	0.723	1.33 (1.56)	0.044*	2.58 (1.94)	0.001*
Right inflammatory disorder
Absence	6.15 (6.19)^a	0.003*	0.30 (1.00)^a	0.339	0.88 (1.44)^a	0.070	1.61 (1.90)^a	0.004*
Arthralgia	11.44 (7.81)^b		0.50 (1.04)^a		1.33 (1.41)^a		2.94 (2.15)^b
Osteoarthrosis	8.21 (6.16)^ab		0.05 (0.22)^a		1.05 (1.50)^a		2.31 (1.76)^ab
Osteoarthritis	9.15 (3.57)^ab		-		1.92 (1.93)^a		2.92 (1.93)^ab
Left inflammatory disorder
Absence	6.30 (6.19)^a	0.008*	0.26 (0.93)^a	0.044*	0.95 (1.50)^a	0.512	1.65 (1.89)^a	0.013*
Arthralgia	11.78 (8.52)^b		0.92 (1.49)^b		1.35 (1.39)^a		2.57 (2.65)^ab
Osteoarthrosis	7.85 (5.91)^ab		0.14 (0.47)^ab		0.85 (1.38)^a		2.38 (1.74)^ab
Osteoarthritis	9.20 (3.88)^ab		-		1.50 (1.65)^a		3.30 (1.82)^b

	OHIP-14
	Physical disability		Psychological disability		Social disability		Handicap
Variables	Mean (SD)	p value	Mean (SD)	p value	Mean (SD)	p value	Mean (SD)	p value
Myofascial Pain
Absence	0.96 (1.84)^a	0.045*	1.43 (1.54)^a	< 0.001*	0.72 (1.01)^a	0.007*	0.38 (0.98)^a	0.034*
Pain	2.11 (2.37)^b		2.83 (1.29)^b		1.38 (0.91)^b		1.05 (1.58)^b
Pain with limitation	0.50 (0.70)^ab		2.50 (0.70)^ab		2.00 (0.00)^ab		0.50 (0.70)^ab
Inflammatory disorder
Absence	0.94 (1.84)	0.124	1.40 (1.56)	0.013*	2.00 (0.00)^ab	0.67 (0.99)	0.50 (0.70)^ab	0.002*	0.39 (1.00)	0.279
Presence	1.39 (2.05)	0.124	2.00 (1.50)	0.013*	1.16 (1.02)	0.57 (1.17)		0.002*		0.279
Right inflammatory disorder
Absence	0.94 (1.83)^a	0.123	1.40 (1.56)^a	0.056	1.16 (1.02)	0.57 (1.17)	0.66 (0.98)^a	0.001*	0.40 (1.00)^a	0.288
Arthralgia	2.05 (2.31)^a		2.22 (1.76)^a		1.50 (0.85)^b	0.88 (1.53)^a
Osteoarthrosis	1.21 (2.29)^a		2.00 (1.41)^a		1.10 (1.28)^ab	0.47 (1.17)^a
Osteoarthritis	0.92 (1.44)^a		2.00 (1.15)^a		1.15 (0.80)^ab	0.30 (0.63)^a
Left inflammatory disorder
Absence	0.98 (1.85)^a	0.142	1.40 (1.54)^a	0.024*	1.15 (0.80)^ab	0.30 (0.63)^a	0.69 (0.98)^a	0.019*	0.38 (0.98)^a	0.095
Arthralgia	2.14 (2.38)^a		2.35 (1.86)^b		1.35 (1.08)^b	1.07 (1.68)^a
Osteoarthrosis	1.14 (2.19)^a		1.90 (1.48)^ab		1.04 (1.20)^ab	0.57 (1.16)^a
Osteoarthritis	0.60 (0.84)^a		2.40 (0.96)^ab		1.30 (0.82)^ab	0.20 (0.42)^a

OHIP-14	IL1B polymorphisms / genotypes		Mean (SD)	p-value
Total scale	rs1143627	AA	5.58 (± 5.12)	0.071
		GA	7.84 (± 7.00)
		GG	7.82 (± 7.37)
	rs1143629	AA	5.92 (± 5.40)	0.118
		AG	6.89 (± 6.16)
		GG	8.31 (± 8.13)
Functional limitation	rs1143627	AA	0.27 (± 1.02)	0.592
		GA	0.38 (± 1.11)
		GG	0.21 (± 0.70)
	rs1143629	AA	0.32 (± 1.00)	0.969
		AG	0.28 (± 1.05)
		GG	0.29 (± 0.86)
Physical pain	rs1143627	AA	0.70 (± 1.13)	0.064
		GA	1.05 (± 1.59)
		GG	1.35 (± 1.73)
	rs1143629	AA	0.72 (± 1.13)a	0.035*
		AG	0.94 (± 1.58)ab
		GG	1.40 (± 1.72)b
Psychological discomfort	rs1143627	AA	1.63 (± 1.76)	0.393
		GA	2.07 (± 2.12)
		GG	1.80 (± 2.05)
	rs1143629	AA	1.71 (± 1.73)	0.536
		AG	2.03 (± 1.98)
		GG	1.74 (± 2.20)
Physical disability	rs1143627	AA	0.72 (± 1.48)	0.154
		GA	1.24 (± 2.14)
		GG	1.33 (± 2.14)
	rs1143629	AA	0.83 (± 1.59)a	0.042*
		AG	0.89 (± 1.84)ab
		GG	1.63 (± 2.37)b
Psychological disability	rs1143627	AA	1.29 (± 1.27)	0.205
		GA	1.69 (± 1.66)
		GG	1.74 (± 1.82)
	rs1143629	AA	1.29 (± 1.28)	0.160
		AG	1.54 (± 1.54)
		GG	1.83 (± 1.93)
Social disability	rs1143627	AA	0.72 (± 0.87)	0.314
		GA	0.96 (± 1.08)
		GG	0.76 (± 1.19)
	rs1143629	AA	0.72 (± 0.91)	0.621
		AG	0.88 (± 1.01)
		GG	0.75 (± 1.21)
Handicap	rs1143627	AA	0.30 (± 0.83)	0.310
		GA	0.49 (± 1.19)
		GG	0.60 (± 1.18)
	rs1143629	AA	0.36 (± 0.88)	0.159
		AG	0.39 (± 1.01)
		GG	0.70 (± 1.36)

OHIP-14	IL6 polymorphisms / genotypes		Mean (SD)	p-value
Total scale	rs1800795	CC	7.04 (± 4.83)	0.777
		CG	6.53 (± 5.86)
		GG	7.21 (± 7.10)
	rs1800796	CC	11.00 (± 9.81)	0.198
		CG	6.71 (± 6.56)
		GG	6.76 (± 6.28)
Functional limitation	rs1800795	CC	0.04 (± 0.20)	0.404
		CG	0.29 (± 0.79)
		GG	0.34 (± 1.15)
	rs1800796	CC	0.75 (± 1.75)	0.358
		CG	0.23 (± 0.79)
		GG	0.28 (± 0.96)
Physical pain	rs1800795	CC	1.17 (± 1.55)	0.640
		CG	0.87 (± 1.44)
		GG	1.02 (± 1.52)
	rs1800796	CC	2.00 (± 1.85)	0.081
		CG	1.11 (± 1.78)
		GG	0.86 (± 1.29)
Psychological discomfort	rs1800795	CC	1.78 (± 2.25)	0.939
		CG	1.84 (± 1.87)
		GG	1.92 (± 2.00)
	rs1800796	CC	0.75 (± 0.88)	0.058
		CG	1.52 (± 1.72)
		GG	2.05 (± 2.11)
Physical disability	rs1800795	CC	1.34 (± 1.79)	0.668
		CG	0.94 (± 1.77)
		GG	1.09 (± 2.04)
	rs1800796	CC	2.37 (± 3.11)	0.079
		CG	1.22 (± 2.16)
		GG	0.89 (± 1.72)
Psychological disability	rs1800795	CC	1.73 (± 1.42)	0.451
		CG	1.35 (± 1.52)
		GG	1.60 (± 1.62)
	rs1800796	CC	2.37 (± 1.92)	0.298
		CG	1.44 (± 1.50)
		GG	1.55 (± 1.61)
Social disability	rs1800795	CC	0.52 (± 0.79)	0.411
		CG	0.83 (± 0.98)
		GG	0.82 (± 1.11)
	rs1800796	CC	1.12 (± 1.88)	0.628
		CG	0.85 (± 1.07)
		GG	0.77 (± 0.97)
Handicap	rs1800795	CC	0.60 (± 0.94)	0.669
		CG	0.38 (± 0.91)
		GG	0.45 (± 1.17)
	rs1800796	CC	1.62 (± 1.84)a	0.007*
		CG	0.40 (± 1.01)b
		GG	0.40 (± 1.02)c

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[TFN1] Obtained from database: https://www.ncbi.nlm.nih.gov/snp/

[TFN2] MAF minor allele frequency

[TFN3] H-W Hardy-Weinberg