MTHFR、BMPR1B和TYMS多态性与先天性小耳畸形相关性研究

刘宁; 刘育凤; 隋静; 张艳秋; 马书梅; 吴文娟; 梁戈玉; 谭谦

doi:10.13201/j.issn.1001-1781.2017.06.001

MTHFR、BMPR1B和TYMS多态性与先天性小耳畸形相关性研究

- 1 南京中医药大学附属医院整形外科(南京, 210029);
- 2 东南大学公共卫生学院教育部环境医学工程重点实验室;
- 3 南京中医药大学附属中西医结合鼓楼临床医学院烧伤整形科
基金项目:
江苏省科技支撑计划-社会发展项目 (No:BE2011817)

江苏省六大人才高峰 (No:2013-WSW-053)

详细信息

通讯作者: 谭谦, E-mail:smmutanqian@sina.com

中图分类号: R764.7

收稿日期: 2017-01-09

Polymorphism analysis of MTHFR,BMPR1B and TYMS in microtia

- 1 Department of Plastic Surgery, Hospital of Traditional Chinese Medicine, Nanjing, 210029, China;
- 2 Key Laboratory of Enviromental Medicine Engineering, Ministry of Education, School of Public Health, Southeast University;
- 3 Nanjing Drum Tower Hospital Clinical College of Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine

More Information

Corresponding author: TAN Qian, E-mail: smmutanqian@sina.com

Received Date: 09 January 2017

摘要

摘要: 目的: 探讨MTHFR、BMPR1B和TYMS基因多态性与先天性小耳畸形的相关性。方法: 收集180例小耳畸形患者和141例健康对照,采用多重PCR分析方法对MTHFR rs4846049、BMPR1B rs1434536和TYMS rs2790位点进行基因型检测,采用χ²检验分析各基因型频率和等位基因频率的在病例组和对照组中的分布,采用分层分析探讨3种基因多态性对不同性别先天性小耳畸形发病风险的影响。结果: TYMS 基因rs2790位点基因型频率和等位基因频率分布在病例组与对照组中差异有统计学意义(P<0.05),进一步分层分析发现,TYMS rs2790基因多态性主要增加男性先天性小耳畸形发病风险(P<0.05),与携带AA 基因型的个体相比,携带基因型AG、GG、AG+GG 的个体发病风险分别为对照组的1.93、3.23和2.10倍,95%CI分别为1.07~3.48、1.12~9.33和1.20~3.68。未发现MTHFR rs4846049、BMPR1B rs1434536多态性和先天性小耳畸形有关(P>0.05)。结论: TYMS rs2790基因多态性和男性先天性小耳畸形发生有关。
- 先天性小耳畸形 /
- MTHFR /
- BMPR1B /
- TYMS /
- 基因多态性
Abstract: Objective: To explore the relationship between MTHFR,BMPR1B and TYMS polymorphism and congenitial microtia in Chinese Han population.Method: A total of 180 microtia patients and 141 healthy participants were enrolled in this study.The genotyping of MTHFR rs4846049, BMPR1B rs1434536 and TYMS rs2790 of the participants were examined with multiple PCR. Frequencies and allele distribution of MTHFR rs4846049,BMPR1B rs1434536 and TYMS rs2790 between cases and control were analyzed with Chi-square test.Result: The genotype frequency distribution of TYMS rs27901 polymorphism was significantly different between two groups(P<0.05).Furthermore, gender stratified analysis showed that TYMS rs2790 polymorphism mainly increase the risks of congenitial microtia in male(P<0.05).Compared with AA genotype,the mircotia risks of subjects with AG GG AG+GG raised to 1.93, 3.23 and 2.10 times,respectively(95%CI:1.07-3.48、1.12-9.33 and 1.20-3.68).However,there was no relationship between MTHFR rs4846049, BMPR1B rs1434536 and microtia.Conclusion: The TYMS rs2790 polymorphism may be a risk factor of microtia in male.
- microtia /
- MTHFR /
- BMPR1B /
- TYMS /
- gene polymorphism

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参考文献(32)

[1]	CANFIELD M A, LANGLOIS P H, NGUYEN L M, et al.Epidemiologic features and clinical subgroups of anotia/microtia in Texas.Birth defects research[J].Part A, Clin Molecular Teratol, 2009, 85:905-913.
[2]	BARTEL-FRIEDRICH S.Congenital auricular malformations:description of anomalies and syndromes[J].Facial Plastic Surg:FPS, 2015, 31:567-580.
[3]	ARTUNDUAGA M A, QUINTANILLA-DIECK MDE L, GREENWAY S, et al.A classic twin study of external ear malformations, including microtia[J].New England J Medic 2009, 361:1216-1218.
[4]	LUQUETTI D V, HEIKE C L, HING A V, et al.Microtia:epidemiology and genetics[J].Am J Med Genetics, 2012, 158:124-139.
[5]	NAN X, LIU M, YUAN G.[Relationship between genetic polymorphism of MTHFR C677T and nonsyndromic cleft lip with or without cleft palate in Shanxi Province of China] [J].Chinese J Plastic Surg, 2014, 30:265-269.
[6]	WANG Y, LIU Y, JI W, et al.Variants in MTHFR gene and neural tube defects susceptibility in China[J].Metabolic Brain Disease, 2015, 30:1017-1026.
[7]	刘宁, 刘育凤, 张艳秋, 等.miR-27a基因多态性与先天小耳畸形的相关性研究[J].东南大学学报医学版, 2015, 34 (6):897-902.
[8]	张艳秋, 刘宁, 刘育凤, 等.MTRR和MTHFD1L基因多态性与先天小耳畸形相关性[J].中国公共卫生2016, 32 (3):302-306.
[9]	马书梅, 刘育凤, 刘宁, 等MTHFR 677C-T和1298AC基因多态性与先天性小耳畸形相关性[J].中国公共卫生, 2015, 31 (5):662-665.
[10]	MARQUARDT P, MULLER-HERMELINK H K.Characteristics of T-lymphocytes infiltrating human B-cell lymphomas[J].Environmental Health Perspectives, 1990, 88:233-235.
[11]	MANDOLA M V, STOEHLMACHER J, ZHANG W, et al.A 6bp polymorphism in the thymidylate synthase gene causes message instability and is associated with decreased intratumoral TS mRNA levels[J].Pharmacogenetics, 2004, 4:319-327.
[12]	KIM S R, OZAWA S, SAITO Y, et al.:Fourteen novel genetic variations and haplotype structures of the TYMS gene encoding human thymidylate synthase (TS)[J].Drug metabolism and pharmacokinetics 2006, 21:509-516.
[13]	JOERGER M, HUITEMA A D, BOOT H, et al.Germline TYMS genotype is highly predictive in patients with metastatic gastrointestinal malignancies receiving capecitabine-based chemotherapy[J].Cancer Chemotherapy Pharmacol, 2015, 75:763-772.
[14]	BURDELSKI C, STRAUSS C, TSOURLAKIS M C, et al.Overexpression of thymidylate synthase (TYMS) is associated with aggressive tumor features and early PSA recurrence in prostate cancer[J].Oncotarget, 2015, 6:8377-8387.
[15]	LUO Y, LI Z, CUI S, et al.Retraction note:joint detection of ERCC1, TUBB3, and TYMS guidance selection of docetaxel, 5-fluorouracil and cisplatin (DDP) individual chemotherapy in advanced gastric cancer patients[J].Eur J Med Res, 2010, 20:29-29.
[16]	FUJISHIMA M, INUI H, HASHIMOTO Y, et al.Relationship between thymidylate synthase (TYMS) gene polymorphism and TYMS protein levels in patients with high-risk breast cancer[J].Anticancer Res, 2010, 30:4373-4379.
[17]	LEE S W, CHEN T J, LIN L C, et al.Overexpression of thymidylate synthetase confers an independent prognostic indicator in nasopharyngeal carcinoma[J].Exp Molecu Pathol 2013, 95:83-90.
[18]	KOTOULA V, KRIKELIS D, KARAVASILIS V, et al.Expression of DNA repair and replication genes in non-small cell lung cancer (NSCLC):a role for thymidylate synthetase (TYMS)[J].BMC Cancer, 2012, 12:342-342.
[19]	XU J, TIAN S, YIN Z, et al.MicroRNA-binding site SNPs in deregulated genes are associated with clinical outcome of non-small cell lung cancer[J].Lung Cancer, 2014, 85:442-448.
[20]	SHEN R, LIU H, WEN J, et al.Genetic polymorphisms in the microRNA binding-sites of the thymidylate synthase gene predict risk and survival in gastric cancer[J].Molecular Carcinogenesis, 2015, 54:880-888.
[21]	LEWIS S J, HARBORD R M, HARRIS R, et al.Meta-analyses of observational and genetic association studies of folate intakes or levels and breast cancer risk[J].J National Cancer Institute, 2006, 98:1607-1622.
[22]	MA E, IWASAKI M, KOBAYASHI M, et al.Dietary intake of folate, vitamin B2, vitamin B6, vitamin B12, genetic polymorphism of related enzymes, and risk of breast cancer:a case-control study in Japan[J].Nutrition Cancer, 2009, 61:447-456.
[23]	SWIERKOT J, SLEZAK R, KARPINSKI P, et al.Associations between single-nucleotide polymorphisms of RFC-1, GGH, MTHFR, TYMS, and TCII genes and the efficacy and toxicity of methotrexate treatment in patients with rheumatoid arthritis[J].Polskie Archiwum Medycyny Wewnetrznej, 2015, 125:152-161.
[24]	CHATURVEDI P, TULSYAN S, AGARWAL G, et al.Relationship of MTHFR and NQO1 Pharmacogenetics and Chemotherapy Clinical Outcomes in Breast Cancer Patients[J].Biochemical Genetics, 2015, 53:211-222.
[25]	D'AMICO M, PASTA F, PASTA L.Thrombophilic genetic factors PAI-1 4G-4G and MTHFR 677TT as risk factors of alcohol, cryptogenic liver cirrhosis and portal vein thrombosis, in a Caucasian population[J].Gene, 2015, 568:85-88.
[26]	CHANG C Y, CHEN Y, LAI M T, et al.BMPR1B up-regulation via a miRNA binding site variation defines endometriosis susceptibility and CA125 levels[J].PLoS One, 2013, 8:e80630-e80630.
[27]	PENNEY K L, SINNOTT J A, TYEKUCHEVA S, et al.Association of prostate cancer risk variants with gene expression in normal and tumor tissue[J].Cancer Epidemiol Biomarkers Prev, 2015, 24:255-260.
[28]	MAHDAVI M, NANEKARANI S, HOSSEINI S D.Mutation in BMPR-IB gene is associated with litter size in Iranian Kalehkoohi sheep[J].Animal Reproduction Science, 2014, 147:93-98.
[29]	GRAUL-NEUMANN L M, DEICHSEL A, WILLE U, et al.Homozygous missense and nonsense mutations in BMPR1B cause acromesomelic chondrodysplasia-type Grebe[J].EJHG, 2014, 22:726-733.
[30]	LEHMANN K, SEEMANN P, STRICKER S, et al.Mutations in bone morphogenetic protein receptor 1B cause brachydactyly type A2[J].Proc Natl Acad Sci U S A, 2003, 100:12277-12282.
[31]	BADURA-STRONKA M, MROZ D, BEIGHTON P, et al.Novel mutation in the BMPR1B gene (R486L) in a Polish family and further delineation of the phenotypic features of BMPR1B-related brachydactyly.Birth defects research[J].Part A, Clin Molecul Teratol, 2015, 103:567-572.
[32]	RACACHO L, BYRNES A M, MACDONALD H, et al.Two novel disease-causing variants in BMPR1B are associated with brachydactyly type A1[J].EJHG, 2015, 23:1640-1645.