Association between SNPs in genes involved in folate metabolism and preterm birth risk.
We investigated the association between 12 single nucleotide polymorphisms (SNPs) in 11 genes involved in folate metabolic and preterm birth. A subset of SNPs selected from 11 genes/loci involved in the folic acid metabolism pathway were subjected to SNaPshot analysis in a case-control study. Twelve SNPs (CBS-C699T, DHFR-c594+59del19, GST01-C428T, MTHFD-G1958A, MTHFR-C677T, MTHFR-A1298C, MTR-A2756G, MTRR-A66G, NFE2L2-ins1+C11108T, RFC1-G80A, TCN2-C776G, and TYMS-1494del6) in 503 DNA samples were simultaneously tested, and included 315 preterm births and 188 controls. None of the 12 SNP genotype distributions related to the folic acid metabolism pathway showed a significant difference between preterm and term babies. The frequency of the compound mutation genotype of MTHFD-G1958A, MTR-A2756G and RFC1-G80A in preterm babies was 7.3%, which was significantly higher than the 2.7% in term babies. Seven babies carried the compound mutation genotype of MTHFD-G1958A, MTR-A2756G, and CBS-C699T, but this was not observed in term babies. The frequency of the combined wild-type genotype of MTHFD-G1958A, MTR-A2756G, MTRR-A66G, MTHFR-A1298C, NFE2L2-ins1+C11108T, and RFC1- G80A in preterm babies was 3.17%, which was significantly lower than the 7.4% in term babies. The 12 SNPs screened in this study were not independent risk factors of preterm birth. Compound mutation genotypes, including MTHFD-G1958A, MTR-A2756G, and RFC1- G80A and MTHFD-G1958A, MTR-A2756G, and CBS-C699T, may increase the risk of preterm birth. The combined wild-type genotype MTHFD-G1958A, MTR-A2756G, MTRR-A66G, MTHFR-A1298C, NFE2L2-ins1+C11108T, and RFC1-G80A may decrease the risk of preterm birth.
Department of Gynaecology and Obstetrics, Center for Reproduction and Genetics, Suzhou Hospital Affiliated to Nanjing Medical University, Suzhou, China.
B J
BJ
Wang
Department of Gynaecology and Obstetrics, Center for Reproduction and Genetics, Suzhou Hospital Affiliated to Nanjing Medical University, Suzhou, China.
M J
MJ
Liu
Department of Gynaecology and Obstetrics, Center for Reproduction and Genetics, Suzhou Hospital Affiliated to Nanjing Medical University, Suzhou, China.
Y
Y
Wang
Department of Gynaecology and Obstetrics, Center for Reproduction and Genetics, Suzhou Hospital Affiliated to Nanjing Medical University, Suzhou, China.
J R
JR
Dai
Department of Gynaecology and Obstetrics, Center for Reproduction and Genetics, Suzhou Hospital Affiliated to Nanjing Medical University, Suzhou, China.
J Y
JY
Tao
Department of Neonatology, Central Laboratory, Suzhou Hospital Affiliated to Nanjing Medical University, Suzhou, China.
S N
SN
Wang
Center of Medical Genetics, Peking University, Beijing, China.
N
N
Zhong
Department of Neonatology, Central Laboratory, Suzhou Hospital Affiliated to Nanjing Medical University, Suzhou, China cyandzh@sohu.com.
Y
Y
Chen
D013766:5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase / Q000235:genetics*; D005260:Female; D005492:Folic Acid / Q000235:genetics* / Q000378:metabolism; D056726:Genetic Association Studies; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D008754:Methylenetetrahydrofolate Dehydrogenase (NADP) / Q000235:genetics*; D015778:Minor Histocompatibility Antigens; D009154:Mutation; D020641:Polymorphism, Single Nucleotide; D047928:Premature Birth / Q000235:genetics* / Q000473:pathology; D051818:Replication Protein C / Q000235:genetics*; D012307:Risk Factors
D015778:Minor Histocompatibility Antigens; C081632:RFC1 protein, human; D005492:Folic Acid; C539735:MTHFD1 protein, human; D008754:Methylenetetrahydrofolate Dehydrogenase (NADP); D013766:5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase; C585801:MTR protein, human; D051818:Replication Protein C