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Spina Bifida Risk (spina + bifida_risk)
Selected AbstractsMaternal periconceptional vitamin use, genetic variation of infant reduced folate carrier (A80G), and risk of spina bifidaAMERICAN JOURNAL OF MEDICAL GENETICS, Issue 1 2002Gary M. Shaw Abstract Women who consume folic acid in early pregnancy reduced their risks for delivering offspring with neural tube defects (NTDs). The underlying process by which folic acid facilitated this risk reduction is unknown. Investigating genetic variation that influences cellular absorption, transport, and metabolism of folate will help fill this data gap. We focused our studies on a candidate gene that is involved in folate transport, the reduced folate carrier 1 (RFC1). Using data from a California population,based case control interview study (1989,1991 birth cohorts), we investigated whether spina bifida risk was influenced by an interaction between a polymorphism of infant RFC1 at nucleotide 80 (A80G) and maternal periconceptional use of vitamins containing folic acid. Allelic variants of RFC1 were determined by genotyping 133 live-born spina bifida case infants and 188 control infants. The percentages of case infants with the A80/A80, G80/G80, and G80/A80 genotypes were 27.2%, 28.0%, and 44.7%, respectively. The percentages of control infants were similar: 26.1%, 29.3%, and 44.7%. Odds ratios of 1.0 (95% confidence interval 0.5,2.0) for the G80/G80 genotype and 1.1 (0.6,2.0) for the G80/A80 genotype were observed relative to the A80/A80 genotype. Among mothers who did not use vitamins, spina bifida risk was 2.4 (0.8,6.9) for infants with genotype G80/G80 compared to those with A80/A80 genotype. Among mothers who did use vitamins, the risk was 0.5 (0.1,3.1) for infants with the G80/G80 genotype. Although this study did not find an increased spina bifida risk for infants who were heterozygous or homozygous for RFC1 A80G, it did reveal modest evidence for a gene-nutrient interaction between infant homozygosity for the RFC1 G80/G80 genotype and maternal periconceptional intake of vitamins containing folic acid on the risk of spina bifida. © 2002 Wiley-Liss, Inc. [source] A common ABCC2 promoter polymorphism is not a determinant of the risk of spina bifida ,BIRTH DEFECTS RESEARCH, Issue 6 2004Liselotte E. Jensen Abstract BACKGROUND There is compelling evidence that the risk of spina bifida, a malformation of the caudal neural tube, is associated with maternal and/or embryonic disturbances in folate/homocysteine metabolism. Hence, functional variants of genes that influence folate/homocysteine metabolism constitute a biologically plausible group of candidate risk factors for spina bifida and other neural tube defects. One such candidate is ABCC2, the gene encoding ABCC2, (a.k.a. canalicular multispecific organic anion transporter [cMOAT], multidrug resistance related protein 2 [MRP2]), a member of the ABC transporter family that effluxes natural folates and anti-folate drugs such as methotrexate. METHODS The association between the risk of spina bifida and both the maternal and embryonic ABCC2 C(,24)T genotype was evaluated by using the transmission disequilibrium test and log-linear modeling. RESULTS These analyses provided no evidence that the risk of spina bifida was significantly related to either the maternal or embryonic ABCC2 C(,24)T genotype. CONCLUSIONS The results of the present analyses suggest that the C(,24)T variant of the ABCC2 gene is not a major determinant of spina bifida risk. Birth Defects Research (Part A), 2004. © 2004 Wiley-Liss, Inc. [source] Evaluation of infant methylenetetrahydrofolate reductase genotype, maternal vitamin use, and risk of high versus low level spina bifida defects,BIRTH DEFECTS RESEARCH, Issue 3 2003Kelly A. Volcik BACKGROUND Several studies have suggested that homozygosity for the C677T 5,10-methylenetetrahydrofolate reductase (MTHFR) variant is a potential risk factor for neural tube defects (NTDs), as individuals homozygous for the C677T allele have slightly elevated homocysteine concentrations under conditions of low folic acid intake. It has been hypothesized that maternal folic acid supplementation prevents NTDs by partially correcting reduced MTHFR activity associated with the variant form of the enzyme. METHODS Genomic DNA was extracted from newborn screening blood spots obtained from 145 infants with spina bifida (SB) and 260 nonmalformed control infants. The MTHFR C677T genotype was determined by restriction enzyme digestion of PCR amplification products with Hinf1. We investigated whether infant MTHFR genotype influenced the risk for the anatomic level of the SB lesion (high vs. low); we also explored whether maternal vitamin use influenced this risk. RESULTS Compared to controls, the frequency of SB infants with the homozygous 677 TT genotype was greatest in those infants with high level SB defects (26%; odds ratio [OR] = 2.9; 95% confidence interval [CI] = 0.9,10.1) than for those with low level SB defects (22%; OR = 1.8; 95% CI = 0.9,3.2). Furthermore, homozygous 677TT infants whose mothers did not use vitamins containing folic acid had a modestly increased risk of SB (OR = 1.8; 95% CI = 0.8,3.9), with this risk increasing more than three-fold (OR = 5.5; 95% CI = 0.8,28.1) for those infants with high level SB defects whose mothers did not use vitamins. CONCLUSIONS Based upon our observations, it is suggested that the association between the infant MTHFR homozygous variant genotype and spina bifida risk may be conditional upon both lesion level and maternal vitamin use. Birth Defects Research (Part A) 67:154,157, 2003. © 2003 Wiley-Liss, Inc. [source] Orofacial clefts and spina bifida: N -Acetyltransferase phenotype, maternal smoking, and medication useBIRTH DEFECTS RESEARCH, Issue 5 2002Iris A.L.M. Van Rooij Background Orofacial clefts and spina bifida are midline defects with a multifactorial etiology. Maternal smoking and medication use periconceptionally have been studied as risk factors for these malformations. The biotransformation enzyme N -acetyltransferase 2 (NAT2), plays a part in the inactivation of toxic compounds in cigarette smoke and medication. We investigated maternal NAT2 phenotype and the interaction with smoking and medication use periconceptionally on orofacial cleft and spina bifida risk in offspring. Methods In this case-control study of 45 mothers of orofacial cleft children, 39 mothers of spina bifida children and 73 control mothers, NAT2 acetylator status was determined by measuring urinary caffeine metabolites. Results Slow NAT2 acetylators showed no increased risk for orofacial cleft (OR = 1.0, 95% CI: 0.4,2.3) or spina bifida offspring (OR = 0.7, 95% CI: 0.3,1.7) compared to fast NAT2 acetylators. More mothers with orofacial cleft and spina bifida offspring smoked cigarettes (36% and 23% respectively) and used medication periconceptionally (38% and 44% respectively) compared to control mothers (smoking:18%, medication use:19%). No interaction between maternal NAT2 acetylator status and smoking or medication use was observed for orofacial cleft and spina bifida risk. Conclusions Maternal smoking and medication use is associated with orofacial cleft risk as well as medication use is with spina bifida. The maternal NAT2 acetylator status, however, was not associated with an increased risk for orofacial cleft or spina bifida offspring, nor in combination with periconceptional smoking or medication use. Teratology 66:260,266, 2002. © 2002 Wiley-Liss, Inc. [source] | ||||||||||