Infants' MTHFR polymorphisms and nonsyndromic orofacial clefts susceptibility: A meta‐analysis based on 17 case–control studies

American Journal of Medical Genetics, Part A - Tập 158A Số 9 - Trang 2162-2169 - 2012
Yongchu Pan1, Weibing Zhang1, Junqing Ma1, Yifei Du1, Dandan Li1, Qi Cai1, Hongbing Jiang1, Meilin Wang2, Zhengdong Zhang2, Lin Wang1
1Institute of Stomatology, Nanjing Medical University, Nanjing, China
2Department of Epidemiology, Nanjing Medical University, Nanjing, China.

Tóm tắt

AbstractMethylenetetrahydrofolate reductase (MTHFR), an important enzyme in folate metabolism, is thought to be involved in the development of nonsyndromic orofacial clefts (NSOC). However, conflicting results have been achieved when evaluating the associations between infants' MTHFR C677T and A1298C polymorphisms and the risk of NSOC. To obtain more precise estimations of these associations, a meta‐analysis recruiting 17 case–control studies was performed. Among Asians we found that CT heterozygote, TT homozygote, and CT/TT of infants' MTHFR C677T variant could contribute to elevated risks of NSOC, compared with CC wild‐type homozygote (OR = 1.741, 95% CI = 1.043–2.907 for CT vs. CC, OR = 2.311, 95% CI = 1.313–4.041 for TT vs. CC, and OR = 1.740, 95% CI = 1.051–2.882 for CT/TT vs. CC, respectively). Similar effect was also observed on MTHFR 677T T allele, when using C allele as a reference in Asians (OR = 1.420, 95% CI = 1.191–1.693, for T allele vs. C allele). Furthermore, in stratified analysis by types of disease, CT/CC was suggested to confer decreased susceptibility to CL/P under recessive genetic model (OR = 0.854, 95% CI = 0.730–1.000). For MTHFR A1298C, the MTHFR 1298C allele in the case group of Caucasians was significantly lower than that in the control group, suggesting a protective effect against NSOC in Caucasian populations (OR = 0.711, 95% CI = 0.641–0.790, for C allele vs. A allele). In conclusion, the meta‐analysis provided confirmative evidences that infants' MTHFR C677T and A1298C polymorphisms were involved in the development of NSOC. © 2012 Wiley Periodicals, Inc.

Từ khóa


Tài liệu tham khảo

10.1089/gtmb.2008.0115

10.1590/S0100-879X2006005000112

10.1002/ajmg.a.31462

10.1136/bmj.38106.559120.7C

10.1093/ejo/26.1.7

10.1136/jmg.2005.031385

10.1038/ng0595-111

10.1038/sj.ejhg.5201187

10.1007/s003359900838

10.1007/s10006-001-0361-4

10.1089/dna.2010.1185

10.1002/sim.1186

10.1111/j.1600-0722.2010.00729.x

10.1093/ije/dyn098

10.1111/j.1601-0825.2009.01577.x

10.1371/journal.pone.0011493

10.1597/06-151.1

10.1002/1096-8628(20010201)98:4<357::AID-AJMG1108>3.0.CO;2-F

10.14219/jada.archive.2009.0022

10.1002/bdra.20491

10.1016/S0140-6736(09)60695-4

10.1136/jmg.2009.070029

10.1002/ajmg.a.33624

10.1111/j.1601-0825.2010.01741.x

10.1016/j.cccn.2003.09.016

10.1002/humu.9257

10.1038/ng.242

10.1002/(SICI)1096-8628(19981116)80:3<196::AID-AJMG2>3.0.CO;2-V

10.1002/ajmg.a.35257

10.1136/jmg.40.5.e64

10.1016/S1673-8527(08)60116-2

Tolarova MM, 1998, A common mutation in the MTHFR gene is a risk factor for nonsyndromic cleft and palate anomalies, Am J Hum Genet, 63, A27

10.1086/301825

10.1093/aje/kwg005

10.1002/ajmg.a.31684

10.1177/154405910808700202

Wan WD, 2006, Relationship between nonsyndromic cleft lip with or without cleft palate (NSCL/P) and genetic polymorphisms of MTHFR C677T and A1298C, Zhonghua Zheng Xing Wai Ke Za Zhi, 22, 8

10.1111/j.1601-0825.2009.01588.x

10.1111/j.1601-0825.2009.01587.x

10.1073/pnas.061408298

10.1159/000322486