Correlation between HLA-DQB1 and HLA-DRB1 gene polymorphisms and caries: a systematic review and Meta-analysis

doi:10.12016/j.issn.2096-1456.2021.12.004

Abstract

Abstract:

Objective Systematic evaluation of the correlation of HLA-DQB1 and HLA-DRB1 allele polymorphisms with caries, to provide reference for caries prevention and treatment. Methods Relevant literature published before December 2020 was searched in the Cochrane Library, PubMed, Embase, Web of Science, Scopus, CNKI, Wanfang, VIP, and CBM databases. Meta-analysis was performed using the R4.0.2 software to test for heterogeneity and evaluate the publication bias. Results In total,10 case-control studies were included with 564 people in the case group and 676 people in the control group. The results of the Meta-analysis show that: ① HLA-DQB1*02 (OR=0.52, 95%CI=0.29-0.93, P < 0.05) and HLA-DRB1*09 (OR=0.34, 95%CI=0.21-0.58, P < 0.05) are protective factors of dental caries; ② HLA-DRB1*13 (OR=2.96, 95%CI=2.03-4.33, P < 0.05) and HLA-DRB1*14 (OR=1.95, 95%CI=1.26-3.02, P < 0.05) alleles are risk factors for the development of dental caries. The results of the subgroup analysis are: HLA-DRB1*07 is a caries susceptibility factor in the Chinese population (OR=0.48, 95% CI=0.24-0.97, P < 0.05), while it is not statistically significant in the Brazilian and Turkish populations; HLA-DRB1*11 is a caries protective factor in the saliva group (OR=2.26, 95% CI=1.46-3.52, P < 0.05). 3.52, P < 0.001), while it is a caries susceptibility factor in the blood group (OR=0.09, 95% CI=0.12-0.34, P < 0.001). Conclusion HLA-DRB1*13 and HLA-DRB1*14 alleles are caries susceptibility genes, and HLA-DQB1*02 and HLA-DRB1*09 have protective effects on the caries development. HLA-DRB1*07 is a caries susceptibility gene in the Chinese population; HLA-DRB1*11 is a caries protective gene in the saliva group. Due to the limited sample size and quality of the included studies, more high-quality studies will be included later for verification.

Key words: dental caries, genetic susceptibility, gene polymorphism, HLA-DQB1, HLA-DRB1, systematic review, Meta-analysis, case-control study

摘要：

目的系统评价HLA-DQB1和HLA-DRB1等位基因多态性与龋病的相关性,为龋病防治提供参考。方法在Cochrane Library、PubMed、Embase、Web of Science、Scopus、知网、万方、维普、中国生物医学文献数据库中检索2020年12月之前发表的相关文献。采用R4.0.2软件进行Meta分析,进行异质性检验,并评价发表偏倚。结果共纳入10篇病例对照研究,病例组564例,对照组676例。Meta分析结果显示:① HLA-DQB1*02(OR=0.52,95%CI=0.29~0.93,P < 0.05)和HLA-DRB1*09(OR=0.34,95%CI=0.21~0.58,P < 0.05)等位基因是龋保护因素;② HLA-DRB1*13(OR=2.96,95%CI=2.03~4.33,P < 0.05)和HLA-DRB1*14(OR=1.95,95%CI=1.26~3.02,P < 0.05)等位基因是龋易感因素。亚组分析结果: HLA-DRB1*07在中国人群中是龋易感因素(OR=0.48,95%CI=0.24~0.97,P < 0.05),而在巴西人群、土耳其人群中均无统计学意义; HLA-DRB1*11在唾液组中为龋保护因素(OR=2.26,95%CI=1.46~3.52,P < 0.001),而在血液组中为龋易感因素(OR=0.09,95%CI=0.12~0.34,P < 0.001)。结论 HLA-DRB1*13和HLA-DRB1*14等位基因是龋易感因素,HLA-DQB1*02和HLA-DRB1*09是龋保护因素。HLA-DRB1*07在中国人群是龋易感因素;HLA-DRB1*11在唾液组中为龋保护因素。因纳入研究样本量及质量有限,待后期纳入更多高质量研究予以验证。

关键词: 龋病, 遗传易感性, 基因多态性, HLA-DQB1, HLA-DRB1, 系统评价, Meta分析, 病例对照研究

CLC Number:

CHEN Yue,WU Zeyu,MO Yanli,JING Yinghao,LIU Yishan. Correlation between HLA-DQB1 and HLA-DRB1 gene polymorphisms and caries: a systematic review and Meta-analysis[J]. Journal of Prevention and Treatment for Stomatological Diseases, 2021, 29(12): 820-827.

陈越,吴泽钰,貊燕丽,敬英豪,刘奕杉. HLA-DQB1和HLA-DRB1基因多态性与龋病相关性的系统评价与Meta分析[J]. 口腔疾病防治, 2021, 29(12): 820-827.

Figures/Tables 12

References 21

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Author and Year	Country	Sample	ethnicity	Age（Year)	Number of HLA alleles studied	Detection method	Number of case group	Number of control group	NOS score
Ali Hadi Fahad 2019^[8]	Iraq	Saliva	Europa	12-15	5	Not mention	20	20	6
Bagherian 2008^[9]	Iran	Blood	Europa	1-6	5	PCR-SSP PCR-RFLP	44	35	7
Guo 2017^[10]	China	Saliva	Mongolian	0.6-2.5	18	PCR-SSP	122	206	8
Ozawa 2001^[11]	Japan	Saliva	Mongolian	18-28	44	PCR-SSOP	38	62	6
Valarini 2012^[12]	Brazil	Saliva	Europa Negro	15-19	5	PCR-SSP	99	65	6
Vries 1985^[13]	Netherlands	Blood	Europa	Not mention	10	Not mention	33	26	7
Wang 2020^[14]	China	Saliva	Mongolian	6-12	13	PCR-SSP	42	123	8
Yildiz 2009^[15]	Turkey	Blood	Europa	9-17	6	PCR-SSP	46	19	6
Zhang 2017^[16]	China	Saliva	Mongolian	3-6	13	PCR-SSP	40	40	8
Zhang 2018^[17]	China	Saliva	Europa Mongolian	3-5	5	PCR-SSP	80	80	8

Author and Year	Country	Sample	ethnicity	Age（Year)	Number of HLA alleles studied	Detection method	Number of case group	Number of control group	NOS score
Ali Hadi Fahad 2019^[8]	Iraq	Saliva	Europa	12-15	5	Not mention	20	20	6
Bagherian 2008^[9]	Iran	Blood	Europa	1-6	5	PCR-SSP PCR-RFLP	44	35	7
Guo 2017^[10]	China	Saliva	Mongolian	0.6-2.5	18	PCR-SSP	122	206	8
Ozawa 2001^[11]	Japan	Saliva	Mongolian	18-28	44	PCR-SSOP	38	62	6
Valarini 2012^[12]	Brazil	Saliva	Europa Negro	15-19	5	PCR-SSP	99	65	6
Vries 1985^[13]	Netherlands	Blood	Europa	Not mention	10	Not mention	33	26	7
Wang 2020^[14]	China	Saliva	Mongolian	6-12	13	PCR-SSP	42	123	8
Yildiz 2009^[15]	Turkey	Blood	Europa	9-17	6	PCR-SSP	46	19	6
Zhang 2017^[16]	China	Saliva	Mongolian	3-6	13	PCR-SSP	40	40	8
Zhang 2018^[17]	China	Saliva	Europa Mongolian	3-5	5	PCR-SSP	80	80	8

HLA allele subtype		No. of study	Test of correlation		Test of heterogeneity				References
HLA allele subtype		No. of study	OR（95%CI)	P	χ²	I²(%)	P	Model (F/R)	References
HLA-DQB1*02		5	0.52（0.29,0.93)	0.03	0.26	59	0.04	R	[8] [9] [10] [12] [17]
HLA-DQB1*03		3	1.02（0.64,1.64)	0.92	0.32	0	0.85	F	[9] [10] [17]
HLA-DQB1*04		4	1.28（0.78,2.11)	0.33	0.23	0	0.97	F	[8] [10] [12] [17]
HLA-DQB1*05		5	0.97（0.67,1.41)	0.87	2.76	0	0.6	F	[8] [9] [10] [12] [17]
HLA-DQB1*06		5	1.07（0.76,1.49)	0.70	0.85	0	0.93	F	[8] [9] [10] [12] [17]
HLA-DRB1*01		4	1.04（0.69,1.57)	0.84	3.21	7	0.36	F	[10] [13] [14] [16]
HLA-DRB1*03		4	1.24（0.83,1.86)	0.29	2.57	0	0.46	F	[10] [13] [14] [16]
HLA-DRB1*04		8	1.25（0.75,2.09)	0.39	15.33	54	0.03	R	[8] [9] [10] [12] [13] [14] [15] [16]
HLA-DRB1*07	Overall	6	0.73（0.35,1.52)	0.40	0.41	56	0.05	R	[10] [11] [13] [14] [15] [16]
	China	3	0.48（0.24,0.97)	0.04	0.19	47	0.15	F	[10] [14] [16]
	Other countries	3	1.70（0.59,4.87)	0.32	0.14	12	0.32	F	[11] [13] [15]
HLA-DRB1*08		3	0.82（0.45,1.49)	0.50	0.76	0	0.69	F	[10] [14] [16]
HLA-DRB1*09		3	0.34（0.21,0.58)	<0.001	0.28	46	0.15	F	[10] [14] [16]
HLA-DRB1*10		3	0.97（0.53,1.77)	0.92	0.5	0	0.78	F	[10] [14] [16]
HLA-DRB1*11	Overall	4	1.16（0.34,3.95)	0.81	1.30	85	<0.01	R	[10] [14] [15] [16]
	Saliva	3	2.26（1.46,3.52)	<0.001	0	0	0.79	R	[10] [14] [16]
	Blood	1	0.09（0.12,0.34)	<0.001					[15]
HLA-DRB1*12		3	0.80（0.52,1.25)	0.33	0.51	0	0.78	F	[10] [14] [16]
HLA-DRB1*13		3	2.96（2.03,4.33)	<0.001	0	0	0.81	F	[10] [14] [16]
HLA-DRB1*14		3	2.01（1.36,2.97)	<0.001	0.02	11	0.32	F	[10] [14] [16]
HLA-DRB1*15		3	1.15（0.77,1.71)	0.50	0.25	0	0.88	F	[10] [14] [16]
HLA-DRB1*16		2	1.45（0.32,6.48)	0.63	0.87	74	0.05	R	[14] [16]

HLA allele subtype		No. of study	Test of correlation		Test of heterogeneity				References
HLA allele subtype		No. of study	OR（95%CI)	P	χ²	I²(%)	P	Model (F/R)	References
HLA-DQB1*02		5	0.52（0.29,0.93)	0.03	0.26	59	0.04	R	[8] [9] [10] [12] [17]
HLA-DQB1*03		3	1.02（0.64,1.64)	0.92	0.32	0	0.85	F	[9] [10] [17]
HLA-DQB1*04		4	1.28（0.78,2.11)	0.33	0.23	0	0.97	F	[8] [10] [12] [17]
HLA-DQB1*05		5	0.97（0.67,1.41)	0.87	2.76	0	0.6	F	[8] [9] [10] [12] [17]
HLA-DQB1*06		5	1.07（0.76,1.49)	0.70	0.85	0	0.93	F	[8] [9] [10] [12] [17]
HLA-DRB1*01		4	1.04（0.69,1.57)	0.84	3.21	7	0.36	F	[10] [13] [14] [16]
HLA-DRB1*03		4	1.24（0.83,1.86)	0.29	2.57	0	0.46	F	[10] [13] [14] [16]
HLA-DRB1*04		8	1.25（0.75,2.09)	0.39	15.33	54	0.03	R	[8] [9] [10] [12] [13] [14] [15] [16]
HLA-DRB1*07	Overall	6	0.73（0.35,1.52)	0.40	0.41	56	0.05	R	[10] [11] [13] [14] [15] [16]
	China	3	0.48（0.24,0.97)	0.04	0.19	47	0.15	F	[10] [14] [16]
	Other countries	3	1.70（0.59,4.87)	0.32	0.14	12	0.32	F	[11] [13] [15]
HLA-DRB1*08		3	0.82（0.45,1.49)	0.50	0.76	0	0.69	F	[10] [14] [16]
HLA-DRB1*09		3	0.34（0.21,0.58)	<0.001	0.28	46	0.15	F	[10] [14] [16]
HLA-DRB1*10		3	0.97（0.53,1.77)	0.92	0.5	0	0.78	F	[10] [14] [16]
HLA-DRB1*11	Overall	4	1.16（0.34,3.95)	0.81	1.30	85	<0.01	R	[10] [14] [15] [16]
	Saliva	3	2.26（1.46,3.52)	<0.001	0	0	0.79	R	[10] [14] [16]
	Blood	1	0.09（0.12,0.34)	<0.001					[15]
HLA-DRB1*12		3	0.80（0.52,1.25)	0.33	0.51	0	0.78	F	[10] [14] [16]
HLA-DRB1*13		3	2.96（2.03,4.33)	<0.001	0	0	0.81	F	[10] [14] [16]
HLA-DRB1*14		3	2.01（1.36,2.97)	<0.001	0.02	11	0.32	F	[10] [14] [16]
HLA-DRB1*15		3	1.15（0.77,1.71)	0.50	0.25	0	0.88	F	[10] [14] [16]
HLA-DRB1*16		2	1.45（0.32,6.48)	0.63	0.87	74	0.05	R	[14] [16]