广泛型侵袭性牙周炎患者牙根形态异常与相关致病基因的关联

doi:10.19723/j.issn.1671-167X.2021.01.004

摘要/Abstract

摘要：

目的: 探索广泛型侵袭性牙周炎(generalized aggressive periodontitis,GAgP)患者牙根形态异常与骨代谢或牙根发育相关基因多态性的关联。方法: 纳入179例GAgP患者,平均(27.23±5.19)岁,男 ∶女=67 ∶112,平均存留牙数(26.80±1.84)颗。采用基于基质辅助激光解吸电离飞行时间质谱技术进行 9个与骨代谢和牙根发育相关基因的13个单核苷酸多态性位点(single nucleotide polymorphisms,SNPs)的基因型检测。采用全口根尖片评判牙根形态异常,包括锥根、细长根、冠根比例失调、弯曲根、融合根、后牙根形态异常,分析13个SNPs位点不同基因型根形态异常牙的数量及发生率。结果: GAgP患者根形态异常牙构成比为14.49%(695/4 798颗),平均(3.88±3.84)颗。维生素D受体(vitamin D receptor,VDR)基因rs2228570位点的CC、CT、TT基因型患者根形态异常牙数量分别为(4.66±4.10)、(3.71±3.93)和(2.68±2.68)颗,CC基因型和TT基因型之间差异有统计学意义(t=2.62,P=0.01)。降钙素受体(calcitotin receptor,CTR)基因rs2283002位点CC、CT、TT基因型患者根形态异常数分别为(5.02±3.70)、(3.43±3.95)、(3.05±3.12)颗,CC基因型的根形态异常发病率高于CT和TT基因型(87.86% vs. 65.26%和63.64%,P=0.006,adjusted OR=3.71,95%CI:1.45~9.50)。结论: VDR rs2228570及CTR rs2283002位点可能与广泛型侵袭性牙周炎患者牙根形态异常的发生有关,值得进一步研究。

关键词: 侵袭性牙周炎, 牙根形态异常, 基因, 单核苷酸多态性

Abstract:

Objective: To explore the association between the abnormal root morphology and bone metabolism or root development related gene polymorphism in patients with generalized aggressive periodontitis.Methods: In the study, 179 patients with generalized aggressive periodontitis were enrolled, with an average age of (27.23±5.19) years, male / female = 67/112. The average number of teeth remaining in the mouth was (26.80±1.84). Thirteen single nucleotide polymorphisms (SNPs) of nine genes which related to bone metabolism and root development were detected by matrix assisted laser desorption ionization time of flight mass spectrometry (MALDI-TOF-MS). Root abnormalities were identified using periapical radiographs. The abnormal root morphology included cone-rooted teeth,slender-root teeth,short-rooted teeth,curved-rooted teeth,syncretic-rooted molars,and molar root abnormalities. The number of teeth and incidence of abnormal root morphology in different genotypes of 13 SNPs were analyzed.Results: The constituent ratio of root with root abnormality in GAgP patients was 14.49%(695/4 798). The average number of teeth with abnormal root morphology in GAgP was (3.88±3.84). The average number of teeth with abnormal root morphology in CC, CT and TT genotypes in vitamin D receptor (VDR) rs2228570 was (4.66±4.10), (3.71±3.93) and (2.68±2.68). There was significant difference between TT genotype and CC genotype (t = 2.62, P =0.01). The average number of root morphological abnormalities in CC, CT and TT genotypes of Calcitotin Receptor (CTR) gene rs2283002 was (5.02±3.70),(3.43±3.95), and (3.05±3.12). The incidence of root morphological abnormalities in CC genotype was higher than that in the patients with CT and TT, and the difference was statistically significant(87.86% vs. 65.26% & 63.64%, P=0.006,adjusted OR =3.71,95%CI: 1.45-9.50). There was no significant difference in the incidence of abnormal root morphology between CT and TT genotypes.Conclusion: VDR rs2228570 and CTR rs2283002 may be associated with the occurrence of abnormal root morphology in patients with generalized aggressive periodontitis, which is worthy of further research.

Key words: Aggressive periodontitis, Root abnormality, Gene, Single nucleotide polymorphisms

中图分类号:

R394.3

刘建,王宪娥,吕达,乔敏,张立,孟焕新,徐莉,毛铭馨. 广泛型侵袭性牙周炎患者牙根形态异常与相关致病基因的关联[J]. 北京大学学报（医学版）, 2021, 53(1): 16-23.

LIU Jian,WANG Xian-e,LV Da,QIAO Min,ZHANG Li,MENG Huan-xin,XU Li,MAO Ming-xin. Association between root abnormalities and related pathogenic genes in patients with generalized aggressive periodontitis[J]. Journal of Peking University (Health Sciences), 2021, 53(1): 16-23.

图/表 6

表1

图1

表2

表3

GAgP患者9个基因13个SNPs位点不同基因型与牙根形态异常"

SNPs	Gene type	GAgP, n(%)	Cone-rooted teeth of anterior		Teeth of root abnormalities
SNPs	Gene type	GAgP, n(%)	Median(P₂₅, P₇₅)	P	$x -$ ±s/Median(P₂₅, P₇₅)	P
VDR rs2228570	CC	59 (33.91)	0 (0, 2)		4.66±4.10
	CT	90 (51.72)	0 (0, 2)	0.02	3.71±3.93	0.01
	TT	25 (14.37)	0 (0, 0)		2.68±2.68
CTR rs2283002	TT	22 (13.25)	0 (0, 1.25)		3.05±3.12
	CT	95 (57.23)	0 (0, 2)	0.14	3.43±3.95	0.03
	CC	49 (29.52)	0 (0, 2.50)		5.02±3.70
CTR rs2374634	TT	144 (83.72)	0 (0, 2)		3 (0, 6.75)
	TC	25 (14.53)	0 (0, 1)	0.44	4 (0, 5)	0.75
	CC	3 (1.74)	0 (0, 1)		6 (0, 7)
MMP-8 rs11225395	GG	73 (41.01)	0 (0, 2)		4.25±3.95
	AG	88 (49.44)	0 (0, 1)	0.23	3.48±3.70	0.38
	AA	17 (9.55)	0 (0, 3)		4.41±4.18
RANK rs11664594	TT	59 (34.30)	0 (0, 2)		4.17±4.26
	AT	87 (50.58)	0 (0, 2)	0.80	4.18±3.80	0.21
	AA	26 (15.12)	0 (0, 2)		2.73±2.86
DBP rs17467825	AA	77 (44.77)	0 (0, 2)		3.84±3.79
	AG	73 (42.44)	0 (0, 2)	0.72	3.67±3.62	0.45
	GG	22 (12.79)	0 (0, 2.50)		4.86±4.95
DBP rs4588	CC	76 (43.18)	0 (0, 2)		3 (0.25, 6)
	CA	79 (44.89)	0 (0, 2)	0.51	4 (0, 6)	0.93
	AA	21 (11.93)	0 (0, 3)		2 (0, 8.50)
DBP rs7041	TT	97 (55.43)	0 (0, 2)		3.84±3.60
	GT	68 (38.86)	0 (0, 2)	0.39	3.99±4.23	0.75
	GG	10 (5.71)	1.5 (0, 2.50)		4.80±3.82
EGF rs2237051	AA	73 (41.71)	0 (0, 1)		3.89±4.06
	GA	90 (51.43)	0 (0, 2)	0.12	4.01±3.67	0.98
	GG	12 (6.86)	0 (0, 2)		3.83±4.28
BMP2 rs2273073	TT	156 (90.17)	0 (0, 2)	0.81	3.96±3.83	0.97
	GT	17 (9.83)	0 (0, 2)		4.00±4.26
	GG	-	-	-	-	-
S100A8 rs3795391	TT	136 (77.27)	0 (0, 2)	0.76	3.91±3.98	0.99
	TC	40 (22.73)	0 (0, 2)		3.90±3.46
	CC	-	-	-	-	-
S100A8 rs3806232	TT	130 (73.03)	0 (0, 2)	0.41	3.79±4.00	0.63
	CT	48 (26.97)	0 (0, 2)		4.10±3.47
	CC	-	-	-	-	-
Runx2/Cbfa1	CC	87 (49.71)	0 (0, 2)		3.44±3.73
rs6938177	TC	71 (40.57)	0 (0, 3)	0.01	4.65±4.03	0.041
	TT	17 (9.71)	0 (0, 0.50)		2.47±2.62

表3

表4

图2

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Gene	SNPs
VDR	rs2228570
CTR	rs2283002, rs2374634
MMP-8	rs11225395
RANK	rs11664594
DBP	rs17467825, rs4588, rs7041
EGF	rs2237051
BMP2	rs2273073
S100A8	rs3795391, rs3806232
Runx2/Cbfa1	rs6938177

Item	Teeth level, n (%)
Cone-rooted teeth of anterior	214 (31)
Cone-rooted teeth of premolar	160 (23)
Short-rooted teeth	106 (15)
Curved-rooted teeth	85 (12)
Slender-root teeth	53 (8)
Molar root abnormalities	39 (6)
Syncretic-rooted molars	37 (5)
Root abnormalities	695 (100)