Abstract
The C677T and A1298C mutations in the 5,10-methylenetetrahydrofolate reductase (MTHFR) gene are each associated with reduced MTHFR activity. The C677T mutation in the heterozygous and homozygous state correlates with increased enzyme thermolability, with homozygous mutant geno-types showing significantly elevated plasma homocysteine levels and decreased plasma folate levels. The A1298C mutation results in decreased MTHFR activity, but changes in neither homocysteine nor folate levels are associated with A1298C variant genotypes. Our study determined the frequencies of the C677T and A1298C MTHFR mutations for spina bifida (SB) cases, mothers and fathers of SB cases, and controls in Hispanics of Mexican-American descent. In addition, our subject population was further categorized as to whether the spina bifida lesion occurred as an upper or lower level defect, according to the Van Allen 'multi-site closure' model. Hispanic SB cases with upper level defects and their mothers were homozygous for the C677T variant allele at a higher rate than their respective controls (OR = 1.5 [95% CI 0.8-2.9], P = 0.30; OR = 2.3 [1.1-4.8], P = 0.04, respectively), with statistically significant results seen only for the maternal homozygous genotype. Homozygosity for the A1298C mutation was seen at a higher rate only in Hispanic mothers of both upper and lower level SB cases when compared to controls, but these results were not statistically significant. Our study provides evidence that the maternal C677T MTHFR homozygous mutant genotype is a risk factor for upper level spina bifida defects in Hispanics. (C) 2000 Wiley-Liss, Inc.
| Original language | English |
|---|---|
| Pages (from-to) | 21-27 |
| Number of pages | 7 |
| Journal | American Journal of Medical Genetics |
| Volume | 95 |
| Issue number | 1 |
| DOIs | |
| State | Published - Nov 6 2000 |
| Externally published | Yes |
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Keywords
- Hispanics
- Methylenetetrahydrofolate reductase
- Multisite closure model
- Spina bifida
ASJC Scopus subject areas
- Genetics(clinical)
Cite this
Methylenetetrahydrofolate reductase and spina bifida : Evaluation of level of defect and maternal genotypic risk in hispanics. / Volcik, K. A.; Blanton, Susan H; Tyerman, G. H.; Jong, S. T.; Rott, E. J.; Page, T. Z.; Romaine, N. K.; Northrup, H.
In: American Journal of Medical Genetics, Vol. 95, No. 1, 06.11.2000, p. 21-27.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Methylenetetrahydrofolate reductase and spina bifida
T2 - Evaluation of level of defect and maternal genotypic risk in hispanics
AU - Volcik, K. A.
AU - Blanton, Susan H
AU - Tyerman, G. H.
AU - Jong, S. T.
AU - Rott, E. J.
AU - Page, T. Z.
AU - Romaine, N. K.
AU - Northrup, H.
PY - 2000/11/6
Y1 - 2000/11/6
N2 - The C677T and A1298C mutations in the 5,10-methylenetetrahydrofolate reductase (MTHFR) gene are each associated with reduced MTHFR activity. The C677T mutation in the heterozygous and homozygous state correlates with increased enzyme thermolability, with homozygous mutant geno-types showing significantly elevated plasma homocysteine levels and decreased plasma folate levels. The A1298C mutation results in decreased MTHFR activity, but changes in neither homocysteine nor folate levels are associated with A1298C variant genotypes. Our study determined the frequencies of the C677T and A1298C MTHFR mutations for spina bifida (SB) cases, mothers and fathers of SB cases, and controls in Hispanics of Mexican-American descent. In addition, our subject population was further categorized as to whether the spina bifida lesion occurred as an upper or lower level defect, according to the Van Allen 'multi-site closure' model. Hispanic SB cases with upper level defects and their mothers were homozygous for the C677T variant allele at a higher rate than their respective controls (OR = 1.5 [95% CI 0.8-2.9], P = 0.30; OR = 2.3 [1.1-4.8], P = 0.04, respectively), with statistically significant results seen only for the maternal homozygous genotype. Homozygosity for the A1298C mutation was seen at a higher rate only in Hispanic mothers of both upper and lower level SB cases when compared to controls, but these results were not statistically significant. Our study provides evidence that the maternal C677T MTHFR homozygous mutant genotype is a risk factor for upper level spina bifida defects in Hispanics. (C) 2000 Wiley-Liss, Inc.
AB - The C677T and A1298C mutations in the 5,10-methylenetetrahydrofolate reductase (MTHFR) gene are each associated with reduced MTHFR activity. The C677T mutation in the heterozygous and homozygous state correlates with increased enzyme thermolability, with homozygous mutant geno-types showing significantly elevated plasma homocysteine levels and decreased plasma folate levels. The A1298C mutation results in decreased MTHFR activity, but changes in neither homocysteine nor folate levels are associated with A1298C variant genotypes. Our study determined the frequencies of the C677T and A1298C MTHFR mutations for spina bifida (SB) cases, mothers and fathers of SB cases, and controls in Hispanics of Mexican-American descent. In addition, our subject population was further categorized as to whether the spina bifida lesion occurred as an upper or lower level defect, according to the Van Allen 'multi-site closure' model. Hispanic SB cases with upper level defects and their mothers were homozygous for the C677T variant allele at a higher rate than their respective controls (OR = 1.5 [95% CI 0.8-2.9], P = 0.30; OR = 2.3 [1.1-4.8], P = 0.04, respectively), with statistically significant results seen only for the maternal homozygous genotype. Homozygosity for the A1298C mutation was seen at a higher rate only in Hispanic mothers of both upper and lower level SB cases when compared to controls, but these results were not statistically significant. Our study provides evidence that the maternal C677T MTHFR homozygous mutant genotype is a risk factor for upper level spina bifida defects in Hispanics. (C) 2000 Wiley-Liss, Inc.
KW - Hispanics
KW - Methylenetetrahydrofolate reductase
KW - Multisite closure model
KW - Spina bifida
UR - http://www.scopus.com/inward/record.url?scp=0034613964&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0034613964&partnerID=8YFLogxK
U2 - 10.1002/1096-8628(20001106)95:1<21::AID-AJMG6>3.0.CO;2-M
DO - 10.1002/1096-8628(20001106)95:1<21::AID-AJMG6>3.0.CO;2-M
M3 - Article
C2 - 11074490
AN - SCOPUS:0034613964
VL - 95
SP - 21
EP - 27
JO - American Journal of Medical Genetics, Part C: Seminars in Medical Genetics
JF - American Journal of Medical Genetics, Part C: Seminars in Medical Genetics
SN - 1552-4825
IS - 1
ER -