国际口腔医学杂志 ›› 2020, Vol. 47 ›› Issue (4): 397-405.doi: 10.7518/gjkq.2020007

• 论著 • 上一篇    下一篇

亚洲人群干扰素调节因子6基因多态性与非综合征型唇腭裂相关性研究的Meta分析

侯亚丽,马利()   

  1. 山东大学附属省立医院口腔颌面外科 济南 250021
  • 收稿日期:2019-07-05 修回日期:2019-11-27 出版日期:2020-07-01 发布日期:2020-07-10
  • 通讯作者: 马利 E-mail:mali3709@163.com
  • 作者简介:侯亚丽,学士,主管护师,Email:n_houyali@sina.cn
  • 基金资助:
    山东省医药卫生科技发展规划项目(2016WSB01049)

Meta-analysis of the association between interferon regulatory factor 6 gene polymorphisms and non-syndromic cleft lip with or without cleft palate in Asian population

Yali Hou,Li Ma()   

  1. Dept. of Oral and Maxillofacial Surgery, Shandong Provincial Hospital Affiliated to Shandong University, Jinan 250021, China
  • Received:2019-07-05 Revised:2019-11-27 Online:2020-07-01 Published:2020-07-10
  • Contact: Li Ma E-mail:mali3709@163.com
  • Supported by:
    This study was supported by Medicine and Health Science Technology of Shandong Province(2016WSB01049)

摘要:

目的 本研究旨在探讨在亚洲人群中干扰素调节因子6基因(IRF6)的rs2235371和rs642961位点多态性与非综合征型唇腭裂的相关性。方法 数据提取由2位评审者独立完成。用比值比(OR)及其95%置信区间(CI)评价IRF6基因多态性与非综合征型唇腭裂发病风险的关系。采用敏感性分析来评估单项研究对总体估计的影响。采用Egger试验和漏斗图评估出版偏差。结果 IRF6 rs2235371、rs642961位点与唇腭裂风险在杂合子比较中有显著差异。在非综合征型唇腭裂中,对于rs2235371位点,GA、AA和GA+AA基因型与GG基因型的OR(95% CI)分别为0.77(0.73~0.81)、0.53(0.41~0.70)和0.77(0.72~0.81);对于rs642961位点,GA、AA和GA+AA基因型与GG基因型的OR(95% CI)分别为1.34(1.09~1.65)、3.56(2.14~5.92)和1.45(1.19~1.77)。敏感性分析的结果表明,任何一项单独的研究均不能够影响合并的OR。漏斗图和Egger试验均未检测到发表偏倚。结论 IRF6 rs642961位点多态性可能增加亚洲人群非综合征型唇腭裂的发病风险,而rs2235371位点多态性不会增加非综合征型唇腭裂的发病风险。

关键词: 非综合征型唇腭裂, 单核苷酸多态性, 干扰素调节因子6, Meta分析

Abstract:

Objective This Meta-analysis was to investigate the relationship of the interferon regulatory factor 6 (IRF6) gene rs2235371 and rs642961 polymorphism and nonsyndromic cleft lip with or without cleft palate (NSCL/P) in Asian population. Methods Data extraction was independently performed by two reviewers. Odds ratio (OR) and its 95% confidence interval (CI) to estimate the associations between IRF6 genetic polymorphisms and the risk of NSCL/P. Variant effects on NSCL/P were assessed using per-genotype approach. A sensitivity analysis was employed to evaluate the influence of single studies on the overall estimate. Publication bias was assessed using the Egger’s test and funnel plot. Results Significant difference was found between IRF6 rs2235371, rs642961 and cleft lip with or without cleft palate (CL/P) risk in heterozygote comparison. For rs2235371, GA, AA and GA+AA carried respectively, 0.77 (0.73-0.81), 0.53 (0.41-0.70) and 0.77 (0.72-0.81) times lower odds of NSCL/P than GG genotype. For rs642961, GA, AA and GA+AA carried respectively, 1.34 (1.09-1.65), 3.56 (2.14-5.92) and 1.45 (1.19-1.77) times higher odds of NSCL/P than GG genotype. The result of sensitivity analysis indicated that no single study could affect the pooled ORs. In addition, there was not publication bias detected by either the funnel plot or Egger’s test. Conclusion These results suggested that the IRF6 rs642961 polymorphism, but not rs2235371, might increase the risk of NSCL/P in the Asian populations. However, more relevant case-control studies are required to obtain more precise results.

Key words: non-syndromic cleft lip with or without palate, single nucleotide polymorphism, interferon regulatory factor 6, Meta-analysis

中图分类号: 

  • Q754

表 1

纳入研究的相关信息"

第一作者 年限 国家 基因位点 第一作者 年限 国家 基因位点
Srichomthong C 2005 泰国 rs2235371 任红旺 2012 中国 rs642961
马坚 2008 中国 rs2235371 Lu Y 2013 中国 rs2235371
Ali A 2009 印度 rs2235371 Song T 2013 中国 rs2235371
Huang Y 2009 中国 rs2235371 张健 2013 中国 rs2235371
Tang W 2009 中国 rs2235371 Aldhorae KA 2014 也门 rs642961
Pan Y 2010 中国 rs2235371 Mijiti A 2015 中国 rs2235371
rs642961 Kerameddin S 2015 伊朗 rs642961
任红旺 2010 中国 rs642961 田景丰 2015 中国 rs642961
Shi J 2011 中国 rs2235371 Xu W 2016 中国 rs2235371
rs642961 rs2235371
李梦洁 2012 中国 rs2235371

表 2

rs2235371位点IRF6基因型频率及基因型效应分析"

作者 年限 非综合征型唇腭裂 对照 GA/GG AA/GG GA+AA/GG
GA AA GG GA AA GG OR1 95% CI OR2 95% CI OR3 95% CI
Srichomthong C 2005 192 72 93 27 93 99 0.75 0.62, 0.93 0.77 0.51, 1.18 0.81 0.68, 0.95
马坚 2008 212 89 107 16 107 105 0.78 0.63, 0.96 0.33 0.19, 0.55 0.74 0.62, 0.87
Ali A 2009 323 65 252 6 252 71 0.64 0.48, 0.86 0.49 0.17, 1.44 0.64 0.49, 0.85
Huang Y 2009 257 106 133 18 133 124 0.76 0.62, 0.93 0.30 0.18, 0.49 0.72 0.61, 0.85
Tang W 2009 66 31 30 5 30 36 0.85 0.63, 1.16 0.55 0.21, 1.41 0.84 0.65, 1.10
Pan Y 2010 127 40 69 18 69 58 0.65 0.49, 0.88 1.42 0.66, 3.05 0.77 0.61, 0.98
Shi J 2011 173 69 82 22 82 91 0.86 0.68, 1.09 0.88 0.52, 1.50 0.89 0.73, 1.08
李梦洁 2012 106 45 57 4 57 49 0.79 0.60, 1.03 0.38 0.13, 1.12 0.77 0.60, 0.99
Lu Y 2013 236 96 122 18 122 114 0.81 0.68, 0.97 0.42 0.26, 0.67 0.78 0.67, 0.91
Song T 2013 203 72 114 17 114 89 0.73 0.58, 0.91 0.58 0.33, 1.00 0.74 0.62, 0.90
张健 2013 100 41 46 13 46 54 0.79 0.59, 1.05 0.57 0.32, 1.03 0.79 0.63, 0.99
Mijiti A 2015 100 17 80 3 80 20 0.52 0.30, 0.90 1.445 0.16, 13.47 0.57 0.34, 0.96
Xu W 2016 104 44 54 6 54 50 0.83 0.65, 1.06 0.32 0.14, 0.70 0.78 0.62, 0.96
汇总 0.77 0.73, 0.81 0.53 0.41, 0.70 0.77 0.72, 0.81

图 1

IRF6 rs2235371森林图 A:AA与GG;B:GA与GG;C:AA+GA与GG。权重根据随机效应分析确定。"

图 2

IRF6 rs642961森林图 A:AA与GG;B:GA与GG;C:AA+GA与GG。权重根据随机效应分析确定。"

表 3

rs642961位点IRF6基因型频率及基因型效应分析"

作者 年限 非综合征型唇腭裂 对照 GA/GG AA/GG GA+AA/GG
GA AA GG GA AA GG OR1 95% CI OR2 95% CI OR3 95% CI
Pan Y 2010 54 67 6 67 60 67 1.54 1.09, 2.19 6.74 0.83, 54.67 1.60 1.14, 2.24
任红旺 2010 70 88 28 88 98 88 1.52 1.15, 2.01 4.34 2.06, 9.17 1.65 1.29, 2.10
Shi J 2011 62 100 11 100 73 100 1.37 0.99, 1.89 5.60 1.27, 24.69 1.46 1.08, 1.98
任红旺 2012 82 140 53 140 135 140 1.03 0.82, 1.30 4.51 2.49, 8.17 1.28 1.06, 1.54
Aldhorae KA 2014 74 159 9 159 83 159 1.30 1.01, 1.67 2.14 0.84, 5.44 1.32 1.04, 1.68
Kerameddin S 2015 51 88 11 88 62 88 0.91 0.67, 1.22 1.15 0.50, 2.644 0.94 0.72, 1.22
田景丰 2015 36 31 21 31 57 31 2.44 1.61, 3.70 7.27 2.92, 18.12 2.55 1.79, 3.61
汇总 1.34 1.09, 1.65 3.56 2.14, 5.92 1.45 1.19, 1.77

图 3

IRF6 rs2235371的敏感性分析 A:AA与GG;B:GA与GG;C:AA+GA与GG。"

图 4

IRF6 rs642961的敏感性分析 A:AA与GG;B:GA与GG;C:AA+GA与GG。"

图 5

IRF6 rs2235371的漏斗图 A:AA与GG;B:GA与GG;C:AA+GA与GG。ES:95% CI估算值。"

图 6

IRF6 rs642961的漏斗图 A:AA与GG;B:GA与GG;C:AA+GA与GG。ES:95% CI估算值。"

[1] Ma L, Shi B, Zheng Q. Targeted mutations of genes reveal important roles in palatal development in mice[J]. Ann Plast Surg, 2015,74(2):263-268.
doi: 10.1097/SAP.0b013e318295dcb8 pmid: 23851369
[2] Lan Y, Xu J, Jiang R. Cellular and molecular me-chanisms of palatogenesis[J]. Curr Top Dev Biol, 2015,115:59-84.
doi: 10.1016/bs.ctdb.2015.07.002 pmid: 26589921
[3] Cuddapah SR, Kominek S, Grant JH3rd, et al. IRF6 sequencing in interrupted clefting[J]. Cleft Palate Craniofac J, 2016,53(3):373-376.
doi: 10.1597/14-204 pmid: 26090788
[4] Kerameddin S, Namipashaki A, Ebrahimi S, et al. IRF6 is a marker of severity in nonsyndromic cleft lip/palate[J]. J Dent Res, 2015,94(9 Suppl):226S-232S.
doi: 10.1177/0022034515581013 pmid: 25896061
[5] Zucchero TM, Cooper ME, Maher BS, et al. Inter-feron regulatory factor 6 (IRF6) gene variants and the risk of isolated cleft lip or palate[J]. N Engl J Med, 2004,351(8):769-780.
doi: 10.1056/NEJMoa032909 pmid: 15317890
[6] Srichomthong C, Siriwan P, Shotelersuk V. Signi-ficant association between IRF6 820G→A and non-syndromic cleft lip with or without cleft palate in the Thai population[J]. J Med Genet, 2005,42(7):e46.
doi: 10.1136/jmg.2005.032235 pmid: 15994871
[7] Tang W, Du X, Feng F, et al. Association analysis between the IRF6 G820A polymorphism and nons-yndromic cleft lip and/or cleft palate in a Chinese population[J]. Cleft Palate Craniofac J, 2009,46(1):89-92.
doi: 10.1597/07-131.1 pmid: 19115793
[8] Mijiti A, Ling W, Guli, et al. Association of single-nucleotide polymorphisms in the IRF6 gene with non-syndromic cleft lip with or without cleft palate in the Xinjiang Uyghur population[J]. Br J Oral Maxillofac Surg, 2015,53(3):268-274.
doi: 10.1016/j.bjoms.2014.12.008 pmid: 25592222
[9] Shi J, Song T, Jiao X, et al. Single-nucleotide poly-morphisms (SNPs) of the IRF6 and TFAP2A in non-syndromic cleft lip with or without cleft palate (NS-CLP) in a northern Chinese population[J]. Biochem Biophys Res Commun, 2011,410(4):732-736.
doi: 10.1016/j.bbrc.2011.06.006 pmid: 21683068
[10] 李梦洁, 朱文丽, 汪云, 等. IRF6基因rs2235371位点多态性与非综合征性唇裂伴或不伴腭裂的相关性研究[J]. 中华医学遗传学杂志, 2012,29(2):149-154.
Li MJ, Zhu WL, Wang Y, et al. Association between polymorphism of IRF6 rs2235371 locus and non-syndromic cleft lip with or without cleft palate[J]. Chin J Med Genet, 2012,29(2):149-154.
[11] 马坚, 黄永清, 马敏, 等. 中国西部人群IRF6基因V274I位点SNP与非综合征型唇腭裂相关性的研究[J]. 实用口腔医学杂志, 2008,24(3):417-421.
Ma J, Huang YQ, Ma M, et al. Association between IRF6 V274I and non-syndromic cleft lip with or without cleft palate in west Chinese population[J]. J Pract Stomatol, 2008,24(3):417-421.
[12] Huang Y, Wu J, Ma J, et al. Association between IRF6 SNPs and oral clefts in west China[J]. J Dent Res, 2009,88(8):715-718.
doi: 10.1177/0022034509341040 pmid: 19734457
[13] Xu W, Han WT, Lu YP, et al. Association of single-nucleotide polymorphisms, rs2235371 and rs2013162, in the IRF6 gene with non-syndromic cleft palate in northeast China[J]. Genet Mol Res, 2016,15(3). doi: 10.4238/gmr.15038210.
doi: 10.4238/gmr.15038682 pmid: 27706775
[14] Pan Y, Ma J, Zhang W, et al. IRF6 polymorphisms are associated with nonsyndromic orofacial clefts in a Chinese Han population[J]. Am J Med Genet A, 2010,152A(10):2505-2511.
doi: 10.1002/ajmg.a.33624 pmid: 20799332
[15] 张健, 古力巴哈·买买提力, 洪玉. IRF6基因多态性位点与新疆维吾尔族、汉族非综合征性唇腭裂的相关性研究[J]. 中国医科大学学报, 2013,42(5):388-393.
Zhang J, Gulibahua Mai-mai-ti-li, Hong Y. Study of relationship correlation study between the IRF6 gene polymorphism and non-syndromic cleft lip with or without cleft palate in Xinjiang Uygurs and Hans with non-syndromic cleft lip with or without cleft palate[J]. J China Med Univ, 2013,42(5):388-393.
[16] Ali A, Singh SK, Raman R. MTHFR 677TT alone and IRF6 820GG together with MTHFR 677CT, but not MTHFR A1298C, are risks for nonsyndromic cleft lip with or without cleft palate in an Indian po-pulation[J]. Genet Test Mol Biomarkers, 2009,13(3):355-360.
doi: 10.1089/gtmb.2008.0115 pmid: 19419265
[17] Song T, Wu D, Wang Y, et al. SNPs and interaction analyses of IRF6, MSX1 and PAX9 genes in patients with non-syndromic cleft lip with or without palate[J]. Mol Med Rep, 2013,8(4):1228-1234.
doi: 10.3892/mmr.2013.1617 pmid: 23921572
[18] Lu Y, Liu Q, Xu W, et al. TGFA and IRF6 contribute to the risk of nonsyndromic cleft lip with or without cleft palate in northeast China[J]. PLoS One, 2013,8(8):e70754.
doi: 10.1371/journal.pone.0070754 pmid: 23940636
[19] 任红旺, 赵桂治, 黄永清, 等. 干扰素调节因子6基因多态性与非综合征型唇腭裂的相关性研究[J]. 华西口腔医学杂志, 2010,28(4):352-355.
Ren HW, Zhao GZ, Huang YQ, et al. Association between interferon regulatory factor 6 gene polymor-phism and non-syndromic oral clefting[J]. West China J Stomatol, 2010,28(4):352-355.
[20] 任红旺, 黄永清, 王珑. IRF6基因多态性和环境因素与非综合征型唇腭裂的相关性研究[J]. 宁夏医科大学学报, 2012,34(11):1164-1168.
Ren HW, Huang YQ, Wang L. Association of IRF6 gene polymorphism and environment factors with nonsyndromic cleft lip and cleft palate[J]. J Ningxia Med Univ, 2012,34(11):1164-1168.
[21] 田景丰, 魏瑗, 王良, 等. IRF6基因rs642961位点多态性与非综合征性唇裂伴或不伴腭裂的相关性研究[J]. 卫生研究, 2015,44(4):543-548.
Tian JF, Wei Y, Wang L, et al. Relationship between genetic polymorphisms of IRF6 rs642961 and non-sysdromic cleft lip with or without cleft palate[J]. J Hygiene Res, 2015,44(4):543-548.
[22] Aldhorae KA, Böhmer AC, Ludwig KU, et al. Non-syndromic cleft lip with or without cleft palate in arab populations: genetic analysis of 15 risk loci in a novel case-control sample recruited in Yemen[J]. Birth Defects Res A Clin Mol Teratol, 2014,100(4):307-313.
doi: 10.1002/bdra.23221 pmid: 24634360
[23] de Souza LT, Kowalski TW, Ferrari J, et al. Study of IRF6 and 8q24 region in non-syndromic oral clefts in the Brazilian population[J]. Oral Dis, 2016,22(3):241-245.
doi: 10.1111/odi.12432 pmid: 26714022
[24] Sun Y, Huang Y, Yin A, et al. Genome-wide asso-ciation study identifies a new susceptibility locus for cleft lip with or without a cleft palate[J]. Nat Commun, 2015,6:6414.
doi: 10.1038/ncomms7414 pmid: 25775280
[25] Zhou Q, Li M, Zhu W, et al. Association between interferon regulatory factor 6 gene polymorphisms and nonsyndromic cleft lip with or without cleft palate in a Chinese population[J]. Cleft Palate Craniofac J, 2013,50(5):570-576.
doi: 10.1597/12-234 pmid: 23509905
[26] Larrabee YC, Birkeland AC, Kent DT, et al. Association of common variants, not rare mutations, in IRF6 with nonsyndromic clefts in a Honduran popula-tion[J]. Laryngoscope, 2011,121(8):1756-1759.
doi: 10.1002/lary.21870 pmid: 21792966
[27] Jafary F, Nadeali Z, Salehi M, et al. Significant association between nonsyndromic cleft lip with or without cleft palate and IRF6 rs2235371 polymor-phism in Iranian familiar population[J]. Mol Biol (Mosk), 2015,49(6):949-952.
[1] 高洁,马锐,葛振林. 热激活镍钛弓丝矫治效率的系统评价[J]. 国际口腔医学杂志, 2019, 46(4): 393-399.
[2] 潘韦霖,曹钰彬,刘畅,刘济远,李春洁,潘剑,华成舸. 不同翻瓣设计对下颌第三磨牙拔除术后疼痛的影响:系统评价与Meta分析[J]. 国际口腔医学杂志, 2019, 46(2): 142-148.
[3] 黄婕,林云红. 种植体周围角化龈宽度与种植体周围骨高度的相关性[J]. 国际口腔医学杂志, 2019, 46(2): 149-155.
[4] 黎静, 刘星辰, 李佳园, 李小兵. 稳定咬合板治疗慢性颞下颌关节盘不可复性移位的临床随机对照试验的系统评价[J]. 国际口腔医学杂志, 2017, 44(4): 405-410.
[5] 杨春艳, 税艳青. 单核苷酸多态性与慢性牙周炎相关关系的研究进展[J]. 国际口腔医学杂志, 2017, 44(4): 452-458.
[6] 李唐 李春洁 门乙 杨文宾 韩波 李龙江. Meta分析评价全景片在口腔癌下颌骨侵犯中的诊断效能[J]. 国际口腔医学杂志, 2016, 43(1): 26-.
[7] 李蓝江1 许冰莹1 杨春艳2 赵川3 田心2. 基质金属蛋白酶1、3和9基因多态性与云南汉族人群口腔鳞状细胞癌发病风险的相关性研究[J]. 国际口腔医学杂志, 2015, 42(6): 631-634.
[8] 居来提·吐尔逊,古丽,艾尼瓦尔·米吉提,阿地力·莫明. 同源异型盒基因1的基因多态性与非综合征性唇腭裂的关联研究[J]. 国际口腔医学杂志, 2015, 42(5): 510-513.
[9] 杨文宾 李春洁 门乙 韩波 李龙江 潘剑. 保留腮腺咬肌筋膜预防Frey综合征的系统评价与Meta分析[J]. 国际口腔医学杂志, 2013, 40(6): 730-735.
[10] 饶南荃 陈娥 裴君 谢云娜. Vitapex在乳牙根管治疗中疗效的循证医学分析[J]. 国际口腔医学杂志, 2013, 40(2): 162-164.
[11] 安志国1, 张浩2 综述 丁一2审校
. 基因位点单核苷酸多态性与牙周炎易感性的关系[J]. 国际口腔医学杂志, 2008, 35(4): 379-379~382.
[12] 黄永清,石冰,. 干扰素调节因子-6基因多态性与非综合征型唇腭裂的相关性研究[J]. 国际口腔医学杂志, 2007, 34(02): 119-121.
[13] 曹正国 朱光勋 李成章. 基质金属蛋白酶-1启动子基因的单核苷酸多态性及其与牙周病的关系[J]. 国际口腔医学杂志, 2003, 30(06): 420-421.
[14] 李志萍 孙宏晨 欧阳喈. 非综合征型唇腭裂的遗传学研究进展[J]. 国际口腔医学杂志, 2003, 30(05): 365-367.
Viewed
Full text


Abstract

Cited

  Shared   
  Discussed   
[1] 王昆润. 在种植体上制作固定义齿以后下颌骨密度的动态变化[J]. 国际口腔医学杂志, 1999, 26(06): .
[2] 王昆润. 修补颌骨缺损的新型生物学相容材料[J]. 国际口腔医学杂志, 1999, 26(06): .
[3] 汤庆奋,王学侠. 17β-雌二醇对人类阴道和口腔颊粘膜的渗透性[J]. 国际口腔医学杂志, 1999, 26(06): .
[4] 张新春. 桩冠修复与无髓牙的保护[J]. 国际口腔医学杂志, 1999, 26(06): .
[5] 王昆润. 长期单侧鼻呼吸对头颅发育有不利影响[J]. 国际口腔医学杂志, 1999, 26(05): .
[6] 潘劲松. 颈总动脉指压和颈内动脉球囊阻断试验在大脑血液动力学中的不同影响[J]. 国际口腔医学杂志, 1999, 26(05): .
[7] 逄键梁. 两例外胚层发育不良儿童骨内植入种植体后牙槽骨生长情况[J]. 国际口腔医学杂志, 1999, 26(05): .
[8] 彭国光. 颈淋巴清扫术中颈交感神经干的解剖变异[J]. 国际口腔医学杂志, 1999, 26(05): .
[9] 王昆润. 后牙冠根斜形牙折的治疗[J]. 国际口腔医学杂志, 1999, 26(05): .
[10] 轩东英. 不同赋形剂对氢氧化钙抗菌效果的影响[J]. 国际口腔医学杂志, 1999, 26(05): .