Association between Genetic Polymorphisms in RANK, RANKL and OPG and Peri-Implant Diseases in Patients from the Amazon Region

Silva, Raphael Carvalho e; Reis, Marilia Bianchini Lemos; Arid, Juliana; Flores, Elvira Katherine Barriga; Cruz, Giuseppe Valduga; Marañón-Vásquez, Guido A.; Souza, Lizete Karla Filgueiras de; Novaes Jr, Arthur Belém; Queiroz, Alexandra Mussolino de; Küchler, Erika Calvano

doi:10.1590/0103-6440202003002

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Article • Braz. Dent. J. 31 (1) • Jan-Feb 2020 • https://doi.org/10.1590/0103-6440202003002 copy

Association between Genetic Polymorphisms in RANK, RANKL and OPG and Peri-Implant Diseases in Patients from the Amazon Region

Authorship SCIMAGO INSTITUTIONS RANKINGS

Abstract

The present study evaluated polymorphisms in RANK, RANKL and OPG-encoding genes to assess whether they are associated with mucositis and peri-implantitis in a population from the Brazilian Amazon region. One hundred and fourteen patients with dental implants were included in the study. After clinical and radiographic examination, the sample was categorized into 4 groups, according to the peri-implant status: Healthy (n=71), Mucositis (n=30), Peri-implantitis (n=13) and Diseased (Mucositis + Peri-implantitis, n=43). Genomic DNA was extracted from buccal cells from saliva, and the genetic polymorphism in osteoprotegerin (OPG), Kappa nuclear factor activator receptor (RANKL) and nuclear kappa factor activator receptor (RANK) were genotyped by the real time PCR. Univariate and multivariate statistical analyses were performed to compare clinical variables among groups and to evaluate genotypes and alleles distributions and the established alpha was 5%. Age, peri-implant biotype, diabetes and presence of peri-implant biofilm were associated with mucositis (p<0.05) and peri-implantitis (p<0.05). Smoking, alcoholism, and periodontal biofilms were also associated with the presence of peri-implantitis (p<0.05). Univariate and multivariate analysis did not demonstrate an association of peri-implantitis or mucositis with any genetic polymorphism in RANK (rs3826620), RANKL (rs9594738) and OPG (rs2073618) (p>0.05). The studied genetic polymorphism in RANK, RANKL and OPG were not associated with mucositis and peri-implantitis in a Brazilian population from the Amazon region.

Key Words:
dental implants; peri-implantitis; genes; genetic polymorphism; genetics; mucositis.

Characteristics	Healthy (n = 71)	Mucositi s (n = 30)	Peri-implantitis (n = 13)	Diseased † (n = 43)	p values
Characteristics	Healthy (n = 71)	Mucositi s (n = 30)	Peri-implantitis (n = 13)	Diseased † (n = 43)	Healthy vs. Mucositis	Healthy vs. Peri-implantitis	Healthy vs. Diseased†
Age (years)
Min	19	32	27	27	< 0.001*	<0.001*	< 0.001*
Max	82	75	77	77
Median	33	50	52	51
Mean (SD)	35.7 (13.0)	51 (12.5)	50 (14.1)	50.7 (12.9)
Gender n (%)
Male	28 (39.4)	12 (40.0)	6 (46.2)	18 (41.9)	>0.999	0.761	0.845
Female	43 (60.6)	18 (60.0)	7 (53.8)	25 (58.1)	>0.999	0.761	0.845
Thick	56 (78.9)	14 (46.7)	5 (38.5)	19 (44.2)	0.002*	0.005*	< 0.001*
Thin	15 (21.1)	16 (53.3)	8 (61.5)	24 (55.8)	0.002*	0.005*	< 0.001*
Smoker	10 (14.1)	2 (6.7)	7 (53.8)	9 (20.9)	0.502	0.004*	0.438
Non-smoker	61 (85.9)	28 (93.3)	6 (46.2)	34 (79.1)	0.502	0.004*	0.438
Diabetes n (%)2
Yes	1 (1.4)	5 (16.7)	2 (15.4)	7 (16.3)	0.009*	0.061	0.004*
No	70 (98.6)	25 (83.3)	11 (84.6)	36 (83.7)	0.009*	0.061	0.004*
Yes	18 (25.4)	13 (43.3)	9 (69.2)	22 (51.2)	0.099	0.003*	0.008*
No	53 (74.6)	17 (56.7)	4 (30.8)	21 (48.8)	0.099	0.003*	0.008*
Presence	47 (66.2)	29 (96.7)	13 (100.0)	42 (97.7)	< 0.001*	0.016*	< 0.001*
Absence	24 (33.8)	1 (3.3)	0 (0.0)	1 (2.3)	< 0.001*	0.016*	< 0.001*
Alcoholic	15 (21.1)	5 (16.7)	7 (53.8)	12 (27.9)	0.786	0.034*	0.497
Non-alcoholic	56 (78.9)	25 (83.3)	6 (46.2)	31 (72.1)	0.786	0.034*	0.497
Yes	27 (38.0)	13 (43.3)	9 (69.2)	22 (51.2)	0.660	0.065	0.179
No	44 (62.0)	17 (56.7)	4 (30.8)	21 (48.8)	0.660	0.065	0.179

	Healthy (n =71) n (%)	Mucositis (n = 30) n (%)	Periimplantitis (n = 13) n (%)	Diseased† (n = 43) n (%)	p values
	Healthy (n =71) n (%)	Mucositis (n = 30) n (%)	Periimplantitis (n = 13) n (%)	Diseased† (n = 43) n (%)	Healthy vs. Mucositis	Healthy vs. Peri-implantitis	Healthy vs. Diseased†
RANK rs3826620
GG	33 (46.5)	14 (46.7)	9 (69.2)	23 (53.5)	0.978	0.214	0.742
GT	35 (49.3)	15 (50.0)	3 (23.1)	18 (41.9)
TT	3 (4.2)	1 (3.3)	1 (7.7)	2 (4.7)
G	101 (71.1)	43 (71.7)	21 (80.8)	64 (74.4)	> 0.999	0.351	0.648
T	41 (28.9)	17 (28.3)	5 (19.2)	22 (25.6)	> 0.999	0.351	0.648
RANKL rs9594738
CC	34 (47.9)	12 (40.0)	4 (30.8)	16 (37.2)	0.478	0.522	0.420
CT	29 (40.8)	16 (53.3)	7 (53.8)	23 (53.5)
TT	8 (11.3)	2 (6.7)	2 (15.4)	4 (9.3)
C	97 (68.3)	40 (66.7)	15 (57.7)	55 (64.0)	0.870	0.366	0.563
T	45 (31.7)	20 (33.3)	11 (42.3)	31 (36.0)	0.870	0.366	0.563
OPG rs2073618
CC	22 (33.3)	11 (40.7)	6 (60.0)	17 (45.9)	0.703	0.221	0.444
CG	30 (45.5)	12 (44.4)	2 (20.0)	14 (37.8)
GG	14 (21.2)	4 (14.8)	2 (20.0)	6 (16.2)
C	74 (56.1)	34 (63.0)	14 (70.0)	48 (64.9)	0.417	0.332	0.239
G	58 (43.9)	20 (37.0)	6 (30.0)	26 (35.1)

Variables	Univariate analysis		Multivariate analysis
Variables	p value	OR (95% CI)	P value	OR (95% CI)
RANK rs3826620
GG	Reference		Reference
GT	0.444	0.74 (0.34 - 1.61)	0.257	0.51 (0.16 - 1.63)
TT	0.963	0.96 (0.15 - 6.19)	0.414	0.33 (0.02 - 4.71)
RANKL rs9594738
CC	Reference		Reference
CT	0.205	1.69 (0.75 - 3.78)	0.744	1.22 (0.38 - 3.91)
TT	0.929	1.06 (0.28 - 4.06)	0.977	1.03 (0.16 - 6.52)
OPG rs2073618
CC	Reference		Reference
CG	0.270	0.69 (0.25 - 1.48)	0.178	0.43 (0.12 - 1.47)
GG	0.314	0.56 (0.18 - 1.75)	0.146	0.29 (0.05 - 1.54)
Age
≤ 38 years	Reference		Reference
> 38 years	< 0.001*	7.35 (3.09 - 17.51)	0.002*	6.14 (1.95 - 19.38)
Thick	Reference		Reference
Thin	< 0.001*	4.72 (2.06 - 10.80)	0.044*	3.41 (1.03 - 11.24)
Smoking habit
Smoker	Reference		Reference
Non-smoker	0.345	0.62 (0.23 - 1.67)	0.303	0.39 (0.07 - 2.33)
Diabetes
Yes	Reference		Reference
No	0.016*	0.07 (0.01 - 0.62)	0.186	0.05 (0.00 - 4.06)
Periodontal disease
Yes	Reference		Reference
No	0.006*	0.32 (0.15 - 0.72)	0.361	0.56 (0.16 - 1.96)
Peri-implant plaque
Presence	Reference		Reference
Absence	0.003*	0.05 (0.01 - 0.36)	0.015*	0.06 (0.01 - 0.58)
Alcoholic	Reference		Reference
Non-alcoholic	0.410	0.69 (0.29 - 1.66)	0.783	0.82 (0.20 - 3.43)

Fundação Odontológica de Ribeirão Preto Av. do Café, S/N, 14040-904 Ribeirão Preto SP Brasil, Tel.: (55 16) 3602-3982, Fax: (55 16) 3633-0999 - Ribeirão Preto - SP - Brazil
E-mail: bdj@forp.usp.br

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[1] Correspondence: Erika Calvano Küchler, Avenida do Café S/N, 14040-904 Ribeirão Preto, SP, Brasil. Tel: +55-16-3315-3995. e-mail: erikacalvano@gmail.com