叶酸代谢相关基因单核苷酸多态性与先天性心脏病风险的关联

Association of SNPs in genes involved in folate metabolism with the risk of congenital heart disease.

作者信息

Wang Benjing, Liu Minjuan, Yan Wenhua, Mao Jun, Jiang Dong, Li Hong, Chen Ying

机构信息

Center for Reproduction and Genetics, Nanjing Medical University Affiliated Suzhou Hospital , Suzhou, Jiangsu Province 215002 , China.

出版信息

J Matern Fetal Neonatal Med. 2013 Dec;26(18):1768-77. doi: 10.3109/14767058.2013.799648. Epub 2013 Jun 10.

DOI:10.3109/14767058.2013.799648

PMID:23701284

Abstract

OBJECTIVE

To investigate the association of 12 single nucleotide polymorphisms (SNPs) in folate metabolic genes with congenital heart disease (CHD).

METHODS

A total of 160 children with CHD and 188 control children were enrolled. Twelve SNPs related to folate metabolism, including CBS-C699T, DHFR-c594 + 59del19, FOLH1-T1561C, CBS-C699T, DHFR-c594 + 59del19, GSTO1-C428T, MTHFD-G878A and -G1958A, MTHFR-C677T and -A1298C, MTR-A2756G, MTRR-A66G, NFE2L2-ins1 + C11108T, RFC1-G80A, TCN2-C776T and TYMS-1494del6, were genotyped by SNaPShot genotyping technology and confirmed by Sanger sequencing.

RESULTS

There were two SNPs including NFE2L2-ins1 + C11108T and GST01-C428T and two compound mutants for (MTHFD-G1958A, MTHFR-C677T and MTR-A2756G) and (MTHFD-G1958A, RFC1-G80A and MTR-A2756G), which might increase the risk of CHD, and DHFR-c594 + 59del19 might decrease the risk of CHD. The CT genotype of NFE2L2-ins1 + C11108T, OR = 2.15 (95% CI = [1.07, 4.32], p < 0.05). The CT + TT genotype of NFE2L2-ins1 + C11108T, OR = 1.98 (95% CI = [1.00, 3.93], p < 0.05). The TT genotype of GST01-C428T, OR = 3.49, (95CI% = [1.06, 11.5], p < 0.05). The GG genotype of DHFR-c594 + 59del19, OR = 0.46 (CI% = [0.24, 0.87], p < 0.05). The AG + GG genotype of DHFR-c594 + 59del19, OR = 0.53 (CI% = [0.29, 0.96], p < 0.05). The ratios of the two compound mutants for (MTHFD-G1958A, MTHFR-C677T and MTR-A2756G) and (MTHFD-G1958A, RFC1-G80A and MTR-A2756G) in CHD are higher than that in control, p < 0.05 (OR = 2.968, 95% CI = [1.022, 8.613]).

CONCLUSIONS

The CT genotype of NFE2L2-ins1 + C11108T and the TT genotype of GST01-C428T are susceptible factors for CHD. The AG, GG and (AG + GG) genotypes of DHFR-c594 + 59del19 are protective genotypes for CHD. Compound mutants for (MTHFD-G1958A, MTHFR-C677T and MTR-A2756G) and (MTHFD-G1958A, RFC1-G80A and MTR-A2756G) may increase the risk of CHD.

摘要

目的

探讨叶酸代谢基因中的12个单核苷酸多态性（SNP）与先天性心脏病（CHD）的关联。

方法

共纳入160例先天性心脏病患儿和188例对照儿童。采用SNaPShot基因分型技术对12个与叶酸代谢相关的SNP进行基因分型，包括CBS-C699T、DHFR-c594＋59del19、FOLH1-T1561C、CBS-C699T、DHFR-c594＋59del19、GSTO1-C428T、MTHFD-G878A和-G1958A、MTHFR-C677T和-A1298C、MTR-A2756G、MTRR-A66G、NFE2L2-ins1＋C11108T、RFC1-G80A、TCN2-C776T和TYMS-1494del6，并通过Sanger测序进行验证。

结果

NFE2L2-ins1＋C11108T和GST01-C428T这两个SNP以及（MTHFD-G1958A、MTHFR-C677T和MTR-A2756G）和（MTHFD-G1958A、RFC1-G80A和MTR-A2756G）这两个复合突变可能增加CHD风险，而DHFR-c594＋59del19可能降低CHD风险。NFE2L2-ins1＋C11108T的CT基因型，OR＝2.15（95%CI＝[1.07，4.32]，p＜0.05）。NFE2L2-ins1＋C11108T的CT＋TT基因型，OR＝1.98（95%CI＝[1.00，3.93]，p＜0.05）。GST01-C428T的TT基因型，OR＝3.49，（95CI%＝[1.06，11.5]，p＜0.05）。DHFR-c594＋59del19的GG基因型，OR＝0.46（CI%＝[0.24，0.87]，p＜0.05）。DHFR-c594＋59del19的AG＋GG基因型，OR＝0.53（CI%＝[0.29，0.96]，p＜0.05）。CHD中（MTHFD-G1958A、MTHFR-C677T和MTR-A2756G）和（MTHFD-G1958A、RFC1-G80A和MTR-A2756G）这两个复合突变的比例高于对照组，p＜0.05（OR＝2.968，95%CI＝[1.022，8.613]）。

结论

NFE2L2-ins1＋C11108T的CT基因型和GST01-C428T的TT基因型是CHD的易感因素。DHFR-c594＋59del19的AG、GG和（AG＋GG）基因型是CHD的保护性基因型。（MTHFD-G1958A、MTHFR-C677T和MTR-A2756G）和（MTHFD-G1958A、RFC1-G80A和MTR-A2756G）复合突变可能增加CHD风险。