Nicotinamide N-methyl transferase (NNMT) gene polymorphisms and risk for spina bifida.
BACKGROUND
Moderate hyperhomocysteinemia is a known risk factor for NTDs in a variety of experimental model systems and is believed to be important in humans as well. The enzyme nicotinamide N-methyl transferase (NNMT) was identified in a genome-wide linkage scan as being an important regulator of homocysteine homeostasis in a Spanish population, making it an interesting candidate gene for NTDs.


METHODS
We evaluated 11 SNPs (single nucleotide polymorphism) of the NNMT gene in our study population. In this study, 252 cases (infants with spina bifida) and 335 controls (nonmalformed infants), born during the period 1983-1986 in selected counties in California, were genotyped for variants of the NNMT gene. Allelic, genotype, and haplotype associations with spina bifida risk were evaluated and analyzed.


RESULTS
None of the SNPs studied alone showed allelic or genotypic associations with spina bifida. However, the TCAG haplotype for block 3 (rs2852447, ra2852425, rs4646337, and rs11569688) showed a decreased risk for spina bifida among non-Hispanic Whites (OR 0.4; 95%CI: 0.1-1.0).


CONCLUSIONS
No association was found between infant NNMT gene variants and risk for spina bifida in our study population. However, small sample sizes for most variant groups and for phase-unknown haplotype data limited the power of the study.
Center for Environmental and Genetic Medicine, Institute of Biosciences and Technology, Texas A&M University Health Science Center, Houston, Texas 77030, USA.
Wei
W
Lu
Huiping
H
Zhu
Shu
S
Wen
Wei
W
Yang
Gary M
GM
Shaw
Edward J
EJ
Lammer
Richard H
RH
Finnell
D000483:Alleles; D016022:Case-Control Studies; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D007223:Infant; D050903:Nicotinamide N-Methyltransferase / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D017422:Sequence Analysis, DNA; D016135:Spinal Dysraphism / Q000201:enzymology / Q000453:epidemiology / Q000235:genetics*
D050903:Nicotinamide N-Methyltransferase