Interaction of Passive Smoking and Diet Habits on Vitamin D Deficiency among Women of Reproductive Age in Rural Central China.

Objective: Maternal dietary undernutrition is known to be associated with the risk of vitamin D (VD) deficiency. However, whether the risk of VD deficiency in women of reproductive age is influenced by the interaction between passive smoking and inadequate nutrition remains unknown. The aim of this study is to explore the interaction between passive smoking and dietary undernutrition on the risk of VD deficiency. Methods: A population-based case−control study including 1151 non-pregnant women of reproductive age between 18 and 40 years old was conducted in Henan Province, China from 2009 to 2010. Blood samples and information on exposure factors were collected. The prevalence of VD deficiency was estimated based on a result of serum 25-hydroxyvitamin D [25(OH)D] < 26.0 ng/mL. A multivariate logistic regression analysis was performed to explore the risk of VD deficiency. Results: The prevalence of VD deficiency was 61.5%. After adjusting for potential confounding factors, the interactions between passive smoking and no nutritional supplementation, passive smoking and insufficient egg intake, and passive smoking and insufficient milk dairy products intake were associated with the risk of VD deficiency, and the adjusted ORs were 3.40 (95% CI 2.26−5.13), 2.87 (95% CI 2.20−4.10), and 2.18 (95% CI 1.33−3.58), respectively. The interaction coefficients were calculated to be 2.35, 2.79, and 1.70, respectively, indicating there were significant interaction effects, as all of the coefficients were higher than 1. Conclusions: Our findings present that the risk of VD deficiency was potentially influenced by interactions between passive smoking and inadequate nutrition. Passive smoking might strengthen the effect of inadequate nutrition on the risk of VD deficiency among rural women of reproductive age. More attention should be paid to the health education and nutritional status improvement of women of reproductive age, especially in rural areas of developing countries.

Effect of periconceptional folic acid supplementation on the risk of neural tube defects associated with a previous spontaneous abortion or maternal first-trimester fever.

STUDY QUESTION: Does maternal periconceptional no folic acid supplementation have an increased risk of neural tube defects (NTDs) associated with previous spontaneous abortion or first-trimester fever? SUMMARY ANSWER: Maternal periconceptional no folic acid supplementation can increase the risk of NTDs associated with previous spontaneous abortion or first-trimester fever, independent of known confounding factors. WHAT IS KNOWN ALREADY: Maternal periconceptional folic acid deficiency can increase the risk of NTDs. However, whether an interaction between periconceptional no folic acid supplementation and history of spontaneous abortion or first-trimester fever may have an increased risk of NTDs remains unknown. STUDY DESIGN, SIZE, DURATION: A population-based case-control study was performed including 104 nuclear families with offspring with NTDs and 100 control families with normal offspring between 1993 and 2002. PARTICIPANTS/MATERIALS, SETTING, METHODS: We investigated the potential interaction between periconceptional no folic acid use and a maternal history of spontaneous abortion or first-trimester fever in the risk for NTDs. Information on exposure factors was obtained at the onset of pregnancy, and pregnancy outcomes were collected during the first week after delivery or at the time of termination of the pregnancy. A multivariate logistic regression analysis was performed. MAIN RESULTS AND THE ROLE OF CHANCE: The interaction between periconceptional no folic acid use and a maternal history of spontaneous abortion markedly increased the risk of NTDs (adjusted odds ratio (aOR) 18.68, 95% CI, 4.43-78.76) after adjusting for potential confounding factors. The interaction coefficient was found to be 2.08, higher than 1, indicating that there is a significant interaction between two factors. Mothers who did not take periconceptional folic acid and had first-trimester fever had an increased risk of NTDs (aOR 21.81, 95% CI, 8.81-80.73). However, the interaction coefficient was found to be 0.62, less than 1, indicating that there is no significant interaction between two factors. LIMITATIONS, REASONS FOR CAUTION: A potential limitation was that the interval between the previous spontaneous abortion and the beginning of the subsequent pregnancy could not be estimated accurately, but was at least 1 year or more. WIDER IMPLICATIONS OF THE FINDINGS: We emphasize that a previous spontaneous abortion may represent a first occurrence of NTDs rather than be the cause of NTDs. Our findings indicate that mothers with a history of spontaneous abortion are ideal candidates for periconceptional folic acid supplementation. STUDY FUNDING/COMPETING INTEREST(S): This work was supported by National Natural Science Foundation of China (41871360) and Danone Nutrition Center for Dietary Nutrition Research and Education Foundation (DIC2015-05). There are no competing interests to declare.

High Ratios of C20:4n-6/C20:5n-3 and Thromboxane B2 /6-Keto-Prostaglandin F1α in Placenta Are Potential Risk Contributors for Neural Tube Defects: A Case-Control Study in Shanxi Province, China.

BACKGROUND: Neural tube defects (NTDs) are severe congenital malformations. Folate supplementation can reduce the risk, but cannot prevent all NTDs, suggesting other reasons for folate-resistant NTDs. The present study assesses placental fatty acid composition, eicosanoids, and cytokines as risk factors for NTDs in a Chinese population with highly incident NTDs. METHODS: Seventy-seven aborted fetuses with NTDs during the third trimester were cases and 142 healthy newborns were controls. Placental fatty acid composition, eicosanoids, and cytokines were determined by standard methods. RESULTS: The placental C20:4n-6/C20:5n-3 and thromboxane B2 (TXB2 )/6-keto-prostaglandin F1α (6-keto-PGF1α ) ratios were significantly higher for cases than controls (p < 0.001 and 0.05, respectively). For the top versus the lowest tertiles of placental C20:4n-6/C20:5n-3 and TXB2 /6-keto-PGF1α , odds ratios for NTD occurrence were 3.79 (95% confidence interval, 1.60-8.96) (p for trend < 0.01) and 5.52 (95% confidence interval, 2.07-14.74) (p for trend < 0.001), respectively, adjusted for fetal sex as well as maternal age, occupation, parity, smoking, passive smoking, periconceptional folate supplementation, conception season, and tea drinking. The C20:4n-6/C20:5n-3 and TXB2 /6-keto-PGF1α ratios were positively correlated (r = 0.14; p < 0.05). The proportions of C18:2n-6, C18:3n-6, C20:3n-6, C18:3n-3, C20:3n-3, C20:5n-3, and C22:5n-3 were significantly lower in cases than controls, and all negatively associated with NTD occurrence (tertile-specific odds ratios); after adjustment for the potential confounders, these associations remained significant (p for trend < 0.05) except for C20:3n-3. CONCLUSION: High placental ratios of C20:4n-6/C20:5n-3 and TXB2 /6-keto-PGF1α are risk factors for neural tube defects.Birth Defects Research 109:550-563, 2017.© 2017 Wiley Periodicals, Inc.

Effectiveness of Folic Acid Fortified Flour for Prevention of Neural Tube Defects in a High Risk Region.

Despite efforts to tackle folate deficiency and Neural Tube Defects (NTDs) through folic acid fortification, its implementation is still lacking where it is needed most, highlighting the need for studies that evaluate the effectiveness of folic acid fortified wheat flour in a poor, rural, high-risk, NTD region of China. One of the most affected regions, Shanxi Province, was selected as a case study. A community intervention was carried out in which 16,648 women of child-bearing age received fortified flour (eight villages) and a control group received ordinary flour (three villages). NTD birth prevalence and biological indicators were measured two years after program initiation at endline only. The effect on the NTD burden was calculated using the disability-adjusted life years (DALYs) method. In the intervention group, serum folate level was higher than in the control group. NTDs in the intervention group were 68.2% lower than in the control group (OR = 0.313, 95% CI = 0.207-0473, p < 0.001). In terms of DALYs, burden in intervention group was approximately 58.5% lower than in the control group. Flour fortification was associated with lower birth prevalence and burden of NTDs in economically developing regions with a high risk of NTDs. The positive findings confirm the potential of fortification when selecting an appropriate food vehicle and target region. As such, this study provides support for decision makers aiming for the implementation of (mandatory) folic acid fortification in China.

Periconceptional Multivitamin Supplementation Containing Folic Acid and Sex Ratio at Birth in a Chinese Population: a Prospective Cohort Study.

BACKGROUND: To determine whether periconceptional use of multivitamin supplements containing folic acid increases the occurrence of male births in a Chinese population. METHODS: A prospective cohort study was carried out in 18 counties in four provinces of China. Participants were naturally and voluntarily divided into an intervention group (who took a multivitamin pill containing folic acid, n = 25,418) and a control group (who did not take any multivitamin, n = 26,580). Multivitamin supplements containing folic acid was ascertained before pregnancy. Pregnant women were followed through the first trimester of pregnancy and the outcome of pregnancy (i.e. livebirth, stillbirth, or fetal death; sex at birth) was recorded. RESULTS: A total of 52,043 pregnancies and 51,998 births were recorded between September 2000 and August 2002. The proportion of males born to women who did and did not take the multivitamin were 54.8% (n = 13,935) and 54.0% (n = 11,483), respectively. The male to female sex ratios at birth among women who did and did not take the multivitamin were 117:100 and 121:100, respectively. The risk ratio was 1.03 [95% confidence interval 0.99, 1.06] after adjusting for confounding factors. CONCLUSIONS: These findings suggest that periconceptional multivitamin supplementation containing folic acid is not associated with an increased likelihood of male births in a Chinese population. However, these results may have been affected by induced abortion or selective termination of pregnancy, and the findings must therefore be cautiously interpreted.

Expression of aquaporin proteins in vagina of diabetes mellitus rats.

INTRODUCTION: Aquaporins (AQPs) are membrane proteins that facilitate water movement across biological membranes. Vaginal lubrication may be mediated by blood flow and other potential mechanisms related to transudation of fluid. The most common female sexual dysfunction in diabetes is inadequate vaginal lubrication. AIM: To investigate the expression of AQP1-3 in vaginal tissue of diabetes mellitus rats. METHODS: Female Sprague-Dawley rats (N = 20) were randomly divided into group A (12-week-old nondiabetic control, N = 5), group B (16-week-old nondiabetes control, N = 5), group C (12-week-old diabetes mellitus rats, N = 5), and group D (16-week-old diabetes mellitus rats, N = 5). Vaginal fluid was measured by fluid weight absorbed by cotton swabs after pelvic nerve electrostimulation and anterior vaginal tissue was dissected for determining the expression of AQP1-3 by immunohistochemical study and Western blot. MAIN OUTCOME MEASURES: The expression of AQP1-3 was determined in the vagina of diabetes mellitus rats by Western blot. RESULTS: There are no significant differences in serum estradiol concentrations of rats among these groups (P > 0.05). Vaginal fluid was significantly lower in group C (2.7 ± 0.67 mg) and group D (2.5 ± 1.03 mg) than in group A (5.74 ± 1.23 mg) and group B (5.5 ± 1.08 mg) (P < 0.05), respectively. The protein expressions of AQP1-3 were significantly lower in group C (43.40 ± 4.83, 60.60 ± 12.80, and 59.60 ± 6.95) and group D (20.81 ± 2.86, 47.80 ± 11.43, and 54.20 ± 5.26) than in group A (116.62 ± 3.21, 110.81 ± 8.044, and 108.80 ± 4.97) and group B (122.12 ± 14.54, 111.21 ± 15.07, and 106.40 ± 4.16) (P < 0.05), respectively. CONCLUSIONS: Decreased vaginal fluid in diabetes mellitus rats after electrostimulation may be partly due to estrogen-independent decreases of AQP1-3 in vaginal tissue.

Tea drinking as a risk factor for neural tube defects in northern China.

BACKGROUND: Tea catechins inhibit the activity of the enzyme dihydrofolate reductase, which catalyzes the inactive form of folate 7,8-dihydrofolate to the active form of folate 5,6,7,8-tetrahydrofolate. This inhibition leads to disturbance of the folate metabolic pathway and to lower bioavailability of folate to cells; therefore, it may increase the risk of neural tube defects (NTDs) in a developing embryo. We examined the association between tea drinking during the periconceptional period and the risk of NTDs. METHODS: Cases were fetuses or neonates with an NTD as ascertained through a population-based surveillance system in 4 rural counties of Shanxi Province in northern China during 2002 through 2007. Controls were term infants without congenital malformations. Demographic, reproductive, and exposure data were obtained through a face-to-face interview. RESULTS: A total of 631 NTD cases and 857 controls were included in the analysis. Compared with women who did not drink tea during the periconceptional period (487 cases and 688 controls), women who drank tea daily (20 cases and 9 controls) had a 3-fold increased risk (odds ratio = 3.1 [95% confidence interval = 1.4-7.0]) of having an NTD-affected pregnancy. The elevated risk associated with daily tea drinking remained after adjusting for maternal age, educational level, occupation, and periconceptional folic acid supplementation (3.4 [1.4-8.3]). The association was present for all 3 major subtypes of NTDs (ie, anencephaly, spina bifida, and encephalocele). CONCLUSIONS: Daily tea drinking during the periconceptional period was associated with an elevated risk of NTDs in this Chinese population.

Metabonomic study on women of reproductive age treated with nutritional intervention: screening potential biomarkers related to neural tube defects occurrence.

Nutritional intervention is effective in reducing the risk of neural tube defects (NTDs). To determine the effects of nutritional supplementation on human metabolism, a metabonomic study was carried out on 96 women of reproductive age. Subjects with nutritional intervention were given fortified wheat flour (containing folic acid, vitamin B1, vitamin B2, ferric sodium edetate and zinc oxide) for 8 months. Serum metabolic fingerprinting was detected via ultraperformance liquid chromatography in tandem with time-of-flight mass spectrometry (UPLC-TOF MS), and data acquired was processed by multivariate statistical analysis. The result revealed a significant difference between the control and intervention group. Twenty potential biomarkers, including fructose 6-phosphate, sphingosine 1-phosphate, docosahexaenoic acid and hexadecanoic acid, were located and identified by the accurate mass measurement of TOF MS. These compounds are believed to be functionally related to anti-oxidative competence in vivo. In conclusion, metabonomics study is a valuable approach in exploring the effect mechanism of nutritional intervention on NTD prevention.

Association of reduced folate carrier gene polymorphism and maternal folic acid use with neural tube defects.

This study was designed to investigate whether the risk for neural tube defects (NTDs) was associated with reduced folate carrier gene (RFC1 A80G) polymorphism and/or with the interaction between the RFC1 gene and maternal periconceptional use of folic acid. One hundred four nuclear families with NTDs and 100 non-malformed control families were sampled to investigate the potential interaction between maternal or the offspring's RFC1 (A80G) genotypes and the maternal periconceptional use of folic acid through a population-based case-control study. RFC1 (A80G) genotypes were detected using PCR-restricted fragment length polymorphism (PCR-RFLP). Mother who had the GG genotype and did not take folic acid had an elevated risk for NTDs (OR = 5.43, 95% CI = 1.68-18.28) as compared to the mother who had AA or GA genotype and took maternal periconceptional folic acid. The interactive coefficient was 1.12 between maternal GG genotype and the periconceptional folic acid non-use. The risk for having an infant with NTDs was 8.80 (95% CI = 2.83-28.69) for offspring with the GG genotype, as compared to the offspring with AA or GA genotype among the mothers who did not take folic acid supplements. The interactive coefficient was 1.45 for offspring with the GG genotype and without maternal periconceptional supplementation of folic acid. Our findings suggest that there is a potential gene-environment interaction on the risk of NTDs between maternal or offspring RFC1 GG genotype and maternal periconceptional intake of folic acid. The RFC1 is likely to be an important candidate gene in folate transportation and RFC1 GG genotype (A80G) may be associated with an increased risk for NTDs in this Chinese population.

Maternal serum vitamin B12, folate and homocysteine and the risk of neural tube defects in the offspring in a high-risk area of China.

OBJECTIVE: To examine the association between the risk of neural tube defects (NTD) and maternal serum vitamin B12, folate and homocysteine in a high-risk area of China. DESIGN: A case-control study was carried out in Luliang mountain area of Shanxi Province. SUBJECTS/SETTING: A total of eighty-four NTD pregnancies and 110 matched controls were included in the study; their serum vitamin B12 and folate concentrations were measured by chemiluminescent immunoenzyme assay and total homocysteine concentrations by fluorescent polarisation immunoassay. RESULTS: Serum vitamin B12 and folate concentrations were lower in NTD-affected pregnant women than in controls (P < 0.01). Serum total homocysteine was higher in the NTD group than in controls at less than 21 weeks of gestation (P < 0.01). Adjusted odds ratios revealed that women with lower vitamin B12 (adjusted OR=4.96; 95 % CI 1.94, 12.67) and folate (adjusted OR=3.23; 95 % CI 1.33, 7.85) concentrations had a higher risk of NTD compared to controls. Based on dietary analysis, less consumption of meat, egg or milk, fresh vegetables and fruit intake would increase the risk of NTD. CONCLUSIONS: Lower serum concentrations of folate and vitamin B12 are related to the increased risk of NTD in high-risk populations. Both folate and vitamin B12 intake insufficiency could contribute to the increased risk of NTD. A dietary supplement, combining folate and vitamin B12, might be an effective measure to decrease the NTD incidence in these areas.

Prevention of NTDs with periconceptional multivitamin supplementation containing folic acid in China.

BACKGROUND: Maternal nutritional factors seem to contribute substantially to the complex etiologies of NTDs. Foremost among these factors is the periconceptional use of supplementation containing folic acid, which is associated with a reduction in the risk of women having NTD-affected pregnancies. This study was designed to observe the effectiveness of multivitamin supplementation containing folic acid in preventing NTDs in a Chinese population and to detect factors that would impact the effectiveness. METHODS: Through family planning networks, a population-based community intervention study was carried out in 18 counties of China. Participants were divided into an intervention (taking multivitamin) group and a control group, and were followed up according to periconceptional multivitamin supplementation (in general 6 mg) for 2 years. Women who had a pregnancy were followed up from 28 weeks gestation at least to pregnancy termination, and the outcome was recorded. The incidence rate of the two groups and the relative risks were calculated to evaluate the efficacy of the multivitamin supplement in preventing NTDs. RESULTS: During 2000 and 2002, all of the women having pregnancies with birth defects and women whose pregnancies were without any birth defects were interviewed. Nine NTDs were recorded from 25,444 pregnancies (NTD birth prevalence = 0.35/1,000 pregnancies) in the intervention group and 48 NTDs among 26,599 pregnancies (NTD birth prevalence = 1.80/1,000 pregnancies) in the control group. The protective rate was 80.4%. CONCLUSIONS: Periconceptional multivitamin supplementation containing folic acid can prevent the occurrence of NTDs with the beneficial effect dependent on the frequency and timing of the supplementation. Our study suggests that multivitamin supplement containing folic acid taken from a time point of 2 months before conception and continuing until completion of the second month after conception and taken more than five times per week can significantly reduce the risks of NTDs.

Variable contribution of the MTHFR C677T polymorphism to non-syndromic cleft lip and palate risk in China.

Non-syndromic cleft lip with or without cleft palate (nsCL/P) is one of the most common craniofacial malformations among newborn infants. It has been demonstrated that periconceptional folic acid supplementation may reduce the occurrence of offspring with clefts, particularly in the North China; however, the mechanism remains unknown. Our study of a thermolabile polymorphism (C677T) of methylenetetrahydrofolate reductase (MTHFR) gene in 170 Chinese case-parent triads revealed a moderate association between this MTHFR polymorphism and nsCL/P in a population from North China, but not in a population from South China. Moreover, the study revealed that the heterozygous parents in the North were about twice as likely to transmit the high-risk T allele to affected cases, as that observed in the South (OR = 2.24, 95% CI: 1.08-4.65). Thus, the MTHFR polymorphism is a significant risk factor for nsCL/P in this Northern Chinese population. Our study suggested possible genetic heterogeneity in the development of nsCL/P among Northern and Southern populations in China.

Genetic variation of infant reduced folate carrier (A80G) and risk of orofacial defects and congenital heart defects in China.

PURPOSE: This study was designed to investigate whether the risks of congenital heart defects (CHD) and orofacial defects were influenced by a polymorphism of the offspring's RFC1 or by an interaction between the RFC1 gene and maternal periconceptional use of folic acid. METHODS: A case-control study was conducted. A total of 82 families with a child affected by cleft lip with or without cleft palate (CLP), 67 families with a child-affected by CHD, and 100 nonmalformed control families were genotyped using PCR-RFLP. RFC1 G allele was tested through family-based association test. RESULTS: Among mothers who did not use folic acid, the risks of 4.03 (95% CI = 1.33-12.77) for the G80/G80 genotype and 4.14 (95% CI = 1.06-16.82) for the G80/A80 genotype were observed relative to the A80/A80 genotype for CHD offspring. In family-based association tests (FBAT), offspring carrying the G allele for RFC1 is at increased risk for CHD (Z = 2.140, p < .05). No significant association was found between either RFC1 genotype or maternal folic acid supplementation and the risks of CLP. CONCLUSIONS: Our findings suggest that the RFC1 G allele is likely to be an important candidate gene in folate transport and to be associated with risk for CHD. This study found modest evidence for a gene-nutrient interaction between offspring RFC1 genotype and periconceptional intake of folic acid on the risk of congenital heart defects.

[Epidemiological study on reduced folate carrier gene(RFC1 A80G) polymorphism and other risk factors of neural tube defects].

OBJECTIVE: To study the reduced folate carrier gene (RFC1) A80G polymorphism and other factors influence on children with neural tube defects (NTDs) and provide the epidemiological evidence for finding genetic marker of NTDs. METHODS: RFC1(A80G) genotypes were detected using polymerase chain reaction-restriction fragment length polymorphism (RFLP-PCR) for blood DNA of 104 trios with NTDs-affected by child, and the 100 control families without child-affected by any birth defects. We performed the analysis of multifactors logistic regression for RFC1 genotypes and other factors in order to investigate the RFC1 genotype of the nuclear families and maternal periconceptional folic acid supplementation influence on NTDs independently. Transmission/disequilibrium test (TDT) for the RFC1 genotype of NTDs and control pedigree were carried out. RESULTS: The RFC1 G allele frequency of children with NTDs (64.42%) was higher than that of the control children (52.53%), and there was the significant difference between them (chi(2)=5.9198, P<0.05). We observed that the infants of the GG genotype were associated with a 2.56-fold increased risk of NTDs when compared with the AA genotype (95% CI=1.04-6.36), The risk of mothers who did not take folic acid for having an NTDs-affected infants was 7.69 (95% CI=2.86-21.75). There were significant differences between cases and controls in the other risk factors, such as paternal age (> or =30), maternal fever during the early pregnancy, the history of maternal spontaneous abortion. In the logistic regression analysis, of multifactors the three factors, for example, the offspring of the RFC1 GG genotype (OR=2.91, 95% CI=1.35-6.30), maternal periconceptional folic acid supplementation (OR=4.32, 95% CI=1.62-11.55), maternal fever during the early pregnancy, had the statistic significance for the risk of NTDs. There was the evidence of an association between G allele and the risk of the maternal having a child with NTDs (OR=1.56, 95% CI=1.07-2.28) in TDT analysis. CONCLUSION: Our findings indicate that the RFC1 genotype (GG) is a possible susceptible gene marker for an increased NTDs risk in this Chinese population, and there is a potential influence on the risk of NTDs in maternal periconceptional folic acid supplementation, and maternal fever during the early pregnancy.

Interaction between maternal periconceptional supplementation of folic acid and reduced folate carrier gene polymorphism of neural tube defects.

OBJECTIVE: To search the interaction between reduced folate carrier gene (RFC1 A80G) polymorphism of children with neural tube defects (NTDs) and maternal periconceptional no supplementation of folic acid. The purpose is to provide the epidemiological evidence for finding genetic marker of NTDs. METHODS: RFC1 (A80G) genotype was detected using PCR-restricted fragment length polymorphism for the blood DNA of 104 trios with NTDs-affected child, and 100 control families with non-malformed control children. The authors investigated the gene-environment interactions between the offspring RFC1 genotype and maternal periconceptional folic acid supplementation through a case-control study. RESULTS: It was observed that the offspring with the GG genotype were associated with a 2.56-fold increased risk of NTDs when compared to those with the AA genotype (OR = 2.56; 95% CI = 1.04-6.36) in this population under investigation. The risk of mothers who did not take folic acid for having an NTDs-affected infants was 7.69 (95% CI = 2.86-21.75). Among the mothers who did not utilize folic acid supplements, the NTDs risk was 3.30 (95% CI = 1.15-9.65) for offspring with the GG genotype, compared to the reference (AA) genotype. Children who had the GG genotype and whose mothers did not take folic acid had an elevated risk for NTDs (OR = 8.80, 95% CI = 2.86 - 29.82), compared to "offspring with AA or GA genotype" and "maternal folic acid use", the interactive coefficient being 1.45. CONCLUSION: The above findings indicate that the RFC1 genotype (GG) is a possible susceptible gene marker for an increased NTDs risk in Chinese population, and there is a potential gene-nutrient interaction between offspring RFC1 GG genotype and maternal periconceptional intake of folic acid on the risk of NTDs. However,the sample size of this study was limited, a larger sample of population-based study is required to pursue the initial observation.

Reduced folate carrier gene is a risk factor for neural tube defects in a Chinese population.

BACKGROUND: There is a considerable body of data demonstrating that periconceptional supplementation of folic acid can prevent a significant proportion of neural tube defects (NTDs). At present, the mechanism by which folic acid exerts its beneficial effect remains unknown. Folate transporter genes, including the reduced folate carrier gene (RFC1), have been proposed as NTD risk factors. METHODS: The study population included 104 nuclear families with NTDs and 100 nonmalformed control families. We investigated the possible association between a common RFC1 polymorphism (A80G) and NTD risk among offspring, as well as potential gene-environment interactions between the infant RFC1 genotype and maternal periconceptional use of folic acid through a population-based case-control study. RESULTS: We observed that the infants of the GG genotype were associated with a 2.56-fold increased risk of NTDs when compared to the AA genotype (odds ratio [OR], 2.56; 95% confidence interval [CI], 1.04-6.36) in our study population. Among mothers who did not utilize folic acid supplements, the risk for having a child with an NTD was 3.30 (95% CI, 1.15-9.65) for offspring with the GG genotype, compared to the reference (AA) genotype. Children who had the GG genotype and whose mothers did not take folic acid had an elevated risk for NTDs (OR, 8.80; 95% CI, 2.83-28.69), compared to offspring with the AA and GA genotypes whose mothers utilized folic acid supplements. CONCLUSIONS: Our findings suggest that the RFC1 G allele is likely to be an important genetic factor in determining folate transport and subsequently may be a risk factor for NTDs in this Chinese population.

[Study on the association between reduced folate carrier gene polymorphism and congenital heart defects and cleft lip with or without cleft palate].

OBJECTIVE: To study the association between reduced folate carrier gene (RFC1) polymorphism and congenital heart defects (CHD) as well as cleft lip with or without cleft palate (CLP) and to provide epidemiological evidence on genetic markers of CHD and CLP. METHODS: RFC1 (A80G) genotype was detected using RFLP-PCR for blood DNA of the 67 triads with nonsyndromic CHD-affected child, the 82 triads with child-affected cleft lip with or without CLP and the 100 control families without child-affected birth defects. We performed a family-based association test and analyzed the interaction between RFC1 A80G genotype and maternal periconceptional supplementation of folic acid. RESULTS: Offspring of mothers who did not take folic acid had an elevated risk for CHD when comparing with offspring of mothers who did (OR = 2.68, 95% CI: 1.14 - 6.41). There was a statistical association between the risk of CHD and maternal periconceptional folic acid supplementation (chi(2) = 6.213, P < 0.05). In the family-based association test, G allele was positively associated with an increased risk for children CHD (Z = 2.140, P < 0.05) while G allele of RFC1 (A80G) polymorphism might increase the risk for CHD. Elevated risks for either CLP group were not observed between RFC1 genotype using or not using folic acid. CONCLUSION: Our findings suggested that the G allele was likely to be a genetically susceptible allele for CHD. There was possible association between offspring with GG, GA genotype and maternal periconceptional folicacid deficiency.