中国人群细胞黏附相关基因多态性与非综合征型唇腭裂的关联研究

doi:10.3969/j.issn.1671-167X.2016.03.005

北京大学学报(医学版) ›› 2016, Vol. 48 ›› Issue (3): 403-408. doi: 10.3969/j.issn.1671-167X.2016.03.005

中国人群细胞黏附相关基因多态性与非综合征型唇腭裂的关联研究

袁园1，王苹2，吴雅慧3，叶晓茜4,5，黄尚志6，石冰7，王科8，王竹青1，刘冬静1，王子凡9，#br# 吴涛1△，王红1

（1.北京大学公共卫生学院流行病与卫生统计学系，北京 100191； 2.北京市疾病预防控制中心信息统计中心，北京 100013； 3.林口长庚纪念医院医学研究部，中国台湾桃园市 33305； 4.武汉大学口腔医院儿童口腔科，武汉 430079； 5. Mount Sinai Medical Center, New York 10029, USA； 6.中国医学科学院，北京协和医学院基础学院医学遗传学系，北京 100005； 7.四川大学华西口腔医学院口腔颌面外科，口腔疾病研究国家重点实验室，成都 610041； 8.青岛大学医学院口腔外科，山东青岛 266000；9.北京大学基础医学院，北京 100191）

出版日期:2016-06-18 发布日期:2016-06-18
通讯作者: 吴涛 E-mail:twu@bjmu.edu.cn
基金资助:
国家自然科学基金（81573225）资助

Association study between candidate genes involved in cell-cell adhesion and non-syndromic cleft lip with or without cleft palate in Chinese population

YUAN Yuan1, WANG Ping2, WU-CHOU Yah-huei3, YE Xiao-qian4,5, HUANG Shang-zhi6, SHI Bing7, WANG Ke8, WANG Zhu-qing1, LIU Dong-jing1, WANG Zi-fan9,WU Tao1△, WANG Hong1

(1.Department of Epidemiology and Biostatistics, Peking University School of Public Health, Beijing 100191, China; 2. Department of Statistics and Information, Beijing Center for Disease Prevention and Control, Beijing 100013, China; 3. Department of Medical Research, Chang Gung Memorial Hospital, Taoyuan, Taiwan 33305, China; 4. Department of Pediatric Dentistry, Wuhan University School of Stomatology, Wuhan 430079, China; 5. Mount Sinai Medical Center, New York 10029, USA; 6. Department of Medical Genetics, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100005, China; 7. Department of Oral and Maxillofacial Surgery, State Key Laboratory of Oral Disease, West China College of Stomatology, Sichuan University, Chengdu 610041, China; 8.Department of Oral Surgery,Qingdao University Medical College, Qingdao 266000, Shandong, China；9. Peking University School of Basic Medical Sciences, Beijing 100191, China)

Online:2016-06-18 Published:2016-06-18
Contact: WU Tao E-mail:twu@bjmu.edu.cn
Supported by:
Supported by the National Natural Science Foundation of China (81573225)

摘要/Abstract

摘要：

目的：探索中国人群中细胞黏附相关基因多态性与非综合征型唇裂合并或不合并腭裂（isolated non-syndromic cleft lip with or without cleft palate, NSCL/P）的关联关系及可能存在的基因-环境交互作用。方法：对一项国际多中心的全基因组关联研究（genome-wide association study, GWAS）的数据进行再分析，选取其中806个中国人群NSCL/P核心家庭，对该人群的8个细胞黏附相关基因包括CDH1、CTNNB1、PVRL1、PVRL2、PVRL3、ACTN1、VCL、LEF1进行了传递不平衡检验（transmisssion diseqilibrium test, TDT）及基因-环境交互作用分析。环境因素包括患儿母亲孕期吸烟、被动吸烟、饮酒及服用多种维生素。结果：经数据质量控制后，共纳入226个单核苷酸多态性（single nucleotide polymorphisms, SNPs）位点，TDT结果显示，CTNNB1、CDH1、ACTN1基因中有23个SNPs与NSCL/P之间存在关联（P<0.05），但经Bonferroni校正后，这些关联均无统计学意义（P>0.000 2）。基因环境交互作用的分析结果显示，14号染色体的ACTN1基因中rs743127位点与母亲孕期被动吸烟的交互作用具有统计学意义（P=0.000 1），母亲孕期无被动吸烟时携带一个该危险位点的患儿的OR值为0.59（95%CI:0.38-0.90），患儿母亲孕期中有被动吸烟情况时携带一个危险位点的患儿的OR值为2.00（95%CI:1.23-3.26）。而ACTN1基因的rs1475034、rs370535、rs2273419位点、CTNNB1基因的rs106871位点与被动吸烟和PVRL3基因的rs7634000、rs2971366、rs2634553、rs1489032、rs7624812位点与母亲孕期补充维生素的交互作用并无统计学意义（P>0.000 2）。结论：传递不平衡检验未发现所纳入的细胞黏附相关基因多态性与NSCL/P存在关联，但基因环境交互作用分析结果提示，ACTN1基因可能通过基因环境交互作用而影响NSCL/P的发病风险。

关键词: ACTN1, 唇裂, 多态现象, 遗传, 基因相关性研究, 基因-环境交互作用

Abstract:

Objective： To explore the association and gene-environment interaction between single nucleotide polymorphisms (SNPs) involved in cell-cell adhesion and non-syndromic cleft lip with or without cleft palate (NSCL/P) among Chinese population. Methods: A total of 806 NSCL/P trios were drawn by an international consortium, which conducted a genome-wide association study (GWAS) using a case-parent trio design to investigate genes affecting risks to NSCL/P. The transmission disequilibrium test (TDT) was used to explore the association between cell-cell adhesion genes, including CDH1, CTNNB1, PVRL1, PVRL2, PVRL3, ACTN1, VCL, LEF1, and NSCL/P. Conditional Logistic regression models were used to estimate effects on risk of exposed and unexposed children. Four common maternal exposures including maternal smoking, environmental tobacco smoke, alcohol consumption and multivitamin supplementation during pregnancy were included in this study. Results: A total of 226 SNP markers were tested after quality control in this study. Although 23 SNPs in three genes (CTNNB1, CDH1, ACTN1) showed nominal significant association with NSCL/P in the TDT (P<0.05).There were no significant evidence of linkage and association that remained in the transmission disequilibrium test after Bonferroni correction(P>0.000 2). Tests for gene-environment interaction yielded significant results between rs743127 in ACTN1 and environmental tobacco smoke (P=0.000 1) with an estimated OR (case|G and E)=2.00（95%CI: 1.23-3.26） and OR (case|G no E)=0.59 (95%CI: 0.38-0.90). Among the lower P value results in gene-environment tests, there were no significant results between rs1475034, rs370535, rs2273419 in ACTN1, rs106871 in CTNNB1 and environmental tobacco smoke interaction. There were also no significant results between rs7634000, rs2971366, rs2634553, rs1489032, rs7624812 in PVRL3 and multivitamin supplementation during pregnancy in gene-environment tests(P>0.000 2). Conclusion: There is no association between cell-cell adhesion genes, including CDH1, CTNNB1, PVRL1, PVRL2, PVRL3, ACTN1, VCL, LEF1, and NSCL/P when the genes are considered alone. But our results suggest that SNPs in ACTN1 may influence the risk to NSCL/P through gene-environment interaction.

Key words: ACTN1, Cleft lip, Polymorphism, genetic, Genetic association studies, Gene-environment interaction

中图分类号:

R181.33

袁园，王苹，吴雅慧，叶晓茜，黄尚志，石冰，王科，王竹青，刘冬静，王子凡，. 中国人群细胞黏附相关基因多态性与非综合征型唇腭裂的关联研究[J]. 北京大学学报(医学版), 2016, 48(3): 403-408.

YUAN Yuan, WANG Ping, WU-CHOU Yah-huei YE Xiao-qian, HUANG Shang-zhi, SHI Bing, WANG Ke, WANG Zhu-qing, LIU Dong-jing, WANG Zi-fan9,WU Tao, WANG Hong. Association study between candidate genes involved in cell-cell adhesion and non-syndromic cleft lip with or without cleft palate in Chinese population[J]. Journal of Peking University(Health Sciences), 2016, 48(3): 403-408.

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中国人群细胞黏附相关基因多态性与非综合征型唇腭裂的关联研究

Association study between candidate genes involved in cell-cell adhesion and non-syndromic cleft lip with or without cleft palate in Chinese population

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