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1.
Tilley MM Northrup H Au KS 《Birth defects research. Part A, Clinical and molecular teratology》2012,94(1):52-56
BACKGROUND: Among infants born with spina bifida, the most common defect is myelomeningocele (MM). The prevention of MM by maternal periconceptional folic acid (FA) supplementation has been studied extensively. The protective effect provided by FA suggests that the genes involved in folate metabolism, such as cystathionine beta‐synthase (CBS), warrant further investigation. METHODS: This study sequenced the DNA from 96 patients with MM to identify novel potential disease‐causing variants across the 17 exons of the CBS gene. The frequencies of known single nucleotide polymorphisms (SNPs) were identified, and sequences that differed from the reference sequences were considered novel variants. Statistical analysis was performed using two‐sided Fisher's exact test to compare frequencies of SNPs between groups of patients and the known population frequencies. RESULTS: We found a new variant in exon 3 in one patient that results in a G/A change subsequently encoding a stop codon. In addition, we found a new variant in the 3′‐UTR of exon 17. Allele frequencies for 10 known single nucleotide polymorphisms (SNPs) were determined: rs234706, rs72058776, rs1801181, rs6582281, rs71872941, rs12613, rs706208, rs706209, rs73906420, and rs9982921. Of the remaining 48 known SNPs, all tested DNAs were homozygous for the major allele. CONCLUSION: We identified a previously undescribed variant in exon 3 that encodes a stop codon, thus halting downstream translation of the CBS protein. According to the Human Splicing Finder, the 3′‐UTR variant found in exon 17 is predicted to abolish the recognition sites for two splice binding factors, SRp40 and SF2/ASF. The functional significance of the 3′‐UTR mutation needs to be investigated. Birth Defects Research (Part A), 2012. © 2011 Wiley Periodicals, Inc. 相似文献
2.
Mills JL Carter TC Kay DM Browne ML Brody LC Liu A Romitti PA Caggana M Druschel CM 《Human genetics》2012,131(5):739-746
Both taking folic acid-containing vitamins around conception and consuming food fortified with folic acid have been reported
to reduce omphalocele rates. Genetic factors are etiologically important in omphalocele as well; our pilot study showed a
relationship with the folate metabolic enzyme gene methylenetetrahydrofolate reductase (MTHFR). We studied 169 non-aneuploid omphalocele cases and 761 unaffected, matched controls from all New York State births occurring
between 1998 and 2005 to look for associations with single nucleotide polymorphisms (SNPs) known to be important in folate,
vitamin B12, or choline metabolism. In the total study population, variants in the transcobalamin receptor gene (TCblR), rs2232775 (p.Q8R), and the MTHFR gene, rs1801131 (c.1298A>C), were significantly associated with omphalocele. In African-Americans, significant associations
were found with SNPs in genes for the vitamin B12 transporter (TCN2) and the vitamin B12 receptor (TCblR). A SNP in the homocysteine-related gene, betaine-homocysteine S-methyltransferase (BHMT), rs3733890 (p.R239Q), was significantly associated with omphalocele in both African-Americans and Asians. Only the TCblR association in the total population remained statistically significant if Bonferroni correction was applied. The finding
that transcobalamin receptor (TCblR) and transporter (TCN2) SNPs and a BHMT SNP were associated with omphalocele suggests that disruption of methylation reactions, in which folate, vitamin B12, and
homocysteine play critical parts, may be a risk factor for omphalocele. Our data, if confirmed, suggest that supplements containing
both folic acid and vitamin B12 may be beneficial in preventing omphaloceles. 相似文献
3.
Ti Zhang Jiao Lou Rong Zhong Jing Wu Li Zou Yu Sun Xuzai Lu Li Liu Xiaoping Miao Guanglian Xiong 《PloS one》2013,8(4)
Background
Neural Tube Defects (NTDs) are among the most prevalent and most severe congenital malformations worldwide. Polymorphisms in key genes involving the folate pathway have been reported to be associated with the risk of NTDs. However, the results from these published studies are conflicting. We surveyed the literature (1996–2011) and performed a comprehensive meta-analysis to provide empirical evidence on the association.Methods and Findings
We investigated the effects of 5 genetic variants from 47 study populations, for a total of 85 case-control comparisons MTHFR C677T (42 studies; 4374 cases, 7232 controls), MTHFR A1298C (22 studies; 2602 cases, 4070 controls), MTR A2756G (9 studies; 843 cases, 1006 controls), MTRR A66G (8 studies; 703 cases, 1572 controls), and RFC-1 A80G (4 studies; 1107 cases, 1585 controls). We found a convincing evidence of dominant effects of MTHFR C677T (OR 1.23; 95%CI 1.07–1.42) and suggestive evidence of RFC-1 A80G (OR 1.55; 95%CI 1.24–1.92). However, we found no significant effects of MTHFR A1298C, MTR A2756G, MTRR A66G in risk of NTDs in dominant, recessive or in allelic models.Conclusions
Our meta-analysis strongly suggested a significant association of the variant MTHFR C677T and a suggestive association of RFC-1 A80G with increased risk of NTDs. However, other variants involved in folate pathway do not demonstrate any evidence for a significant marginal association on susceptibility to NTDs. 相似文献4.
Xue-bin Wang Chen Qiao Li Wei Ya-di Han Ning-hua Cui Zhu-liang Huang Zu-hua Li Fang Zheng Ming Yan 《PloS one》2015,10(12)
Homocysteine (Hcy) is a potential risk factor for age-related cataract (ARC). Methylenetetrahydrofolate reductase (MTHFR) is the key enzyme for Hcy metabolism, and variants of MTHFR may affect MTHFR enzyme activity. This study mainly evaluated the associations between variants in MTHFR gene, plasma MTHFR enzyme activity, total Hcy (tHcy) levels and ARC risk in Chinese population. Four single nucleotide polymorphisms (SNPs) in MTHFR gene were genotyped using the high-resolution melting (HRM) method in 502 ARC patients (mean age, 70.2 [SD, 9.0], 46.0% male) and 890 healthy controls (mean age, 67.1 [SD, 11.1], 47.6% male). The plasma MTHFR activity, folic acid (FA), vitamins B12 and B6 levels were detected by enzyme-linked immunosorbent assays (ELISA). The plasma tHcy levels were measured by an automated enzymatic assay. After the Bonferroni correction, the minor allele T of SNP rs1801133 showed a significant association with an increased risk of overall ARC (OR = 1.26, P = 0.003). Consistent association was also found between SNP rs1801133 and cortical ARC risk (OR = 1.44, P = 0.003). Haplotype analyses revealed an adverse effect of the haplotype "C-A-T-C" (alleles in order of SNPs rs3737967, rs1801131, rs1801133 and rs9651118) on ARC risk (OR = 1.55, P = 0.003). Moreover, in a joint analysis of SNPs rs9651118 and rs1801133, subjects with two unfavorable genotypes had a 1.76-fold increased risk of ARC compared with the reference group, and a statistically significant dose-response trend (Ptrend = 0.001) was also observed. Further, in healthy controls and patients with cortical ARC, the allele T of SNP rs1801133 and the increasing number of unfavorable genotypes were significantly correlated with decreased MTHFR activity as well as increased tHcy levels. However, there was no significant association between FA, vitamins B12, B6 levels and MTHFR variants. Our data indicated that variants in MTHFR gene might individually and jointly influence susceptibility to ARC by affecting MTHFR enzyme activity and tHcy levels. 相似文献
5.
《Biomarkers》2013,18(1):69-71
A synopsis and meta-analysis of studies that investigated the association between genetic variants involved in the homocysteine/folate metabolism pathway and risk of inflammatory bowel disease (IBD) were conducted. Four variants (MTHFR C6TTT, MTHFR A1298C, MTR A2756G and MTRR A66G) showed significant associations in individual studies. In meta-analyses, only the variant MTR A2756G indicated an association with the risk of IBD for the allele contrast and the dominant model (odds ratio (OR) 1.48 (1.12–1.97) and OR 1.55 (1.12–2.15), respectively). The effect sizes for Crohn’s disease and ulcerative colitis were similar to IBD. Cumulative meta-analysis for C677T indicated a downward trend of association as information accumulates. 相似文献
6.
Along with aging, human body composition undergoes notable changes and may incur sarcopenia, obesity or osteoporosis. Sarcopenia
is related to a wide series of human health problems and can be largely characterized by loss of lean body mass (LBM). Studies
have showed relevance of methylenetetrahydrofolate reductase (MTHFR) with variation in LBM and fat body mass (FBM). To test
if polymorphism of the MTHFR gene is underlying the pathology of sarcopenia and obesity, we concurrently tested five single nucleotide polymorphisms (SNPs)
of the MTHFR gene for association with LBM, FBM and body mass index (BMI) in 405 Caucasian nuclear families comprising 1,873 individuals.
After correction for multiple testing, we detected significant associations for LBM with rs2066470 (P = 0.0006), rs4846048 (P = 0.0007) and with rs3737964 (P = 0.004), as well as for BMI with rs4846048 (P = 0.009). Polymorphism of rs2066470 explains 3.67% of LBM variation in this sample. The association between BMI and rs4846048 diminished after adjusting for LBM, suggesting that the association between BMI and rs4846048 is largely due to LBM instead of the fat component. In concert, no significant associations were identified for FBM with
any of the studied SNPs. The results of single-locus association analyses were corroborated by haplotype-based analyses. In
summary, the MTHFR gene polymorphism is associated with LBM, suggesting that MTHFR may play an important role in LBM variation. In addition,
the MTHFR gene polymorphism is not associated with FBM or obesity in this sample. 相似文献
7.
Pawlik P Mostowska A Lianeri M Sajdak S Kędzia H Jagodzinski PP 《Molecular biology reports》2012,39(5):5553-5560
Data indicates that genetic factors alone do not account for ovarian tumorigenesis, suggesting that epigenetic status additionally
affects this process. Therefore, we assessed the possible contribution of polymorphic variants of genes that may affect DNA
methylation to the risk of ovarian cancer incidence in the Polish population. Using PCR-RFLP and HRM analyses, we studied
the distribution of BHMT (rs3733890), MTHFD1 (rs2236225), MTHFR (rs1801133), MTR (rs1805087), MTRR (rs1801394) and TCN2 (rs1801198) genotypes and alleles in patients with ovarian cancer (n = 136) and controls (n = 160). Moreover, using DNA and methylation-specific PCR (MSP) we also determined the methylation of the Cadherin 13
(CDH13) promoter in cancerous tissue from these patients. We did not observe a significant association between all studied gene variants
and the incidence of ovarian cancer. The lowest P
trend = 0.1226 was observed for the MTHFR Ala222Val polymorphism. Moreover, the lowest P = 0.0772 was found in the comparison of MTHFR Ala/Ala versus Val/Val and Val/Ala genotypes in patients and control groups. The multifactor dimensionality reduction analysis
also did not indicate a significant interactive genetic effect on ovarian cancer incidence for all analyzed SNPs. However,
we observed frequent methylation of the CDH13 promoter in approximately 21% (29/136) patients with ovarian carcinomas. Our results might suggest that the selected polymorphic
gene variants may not contribute to ovarian cancer incidence. 相似文献
8.
Catherine J. Spellicy Hope Northrup Jack M. Fletcher Paul T. Cirino Maureen Dennis Alanna C. Morrison Carla A. Martinez Kit Sing Au 《PloS one》2012,7(12)
The objective of this study was to examine the relation between the 5, 10-methylenetetrahydrofolate reductase (MTHFR) gene and behaviors related to attention- deficit/hyperactivity disorder (ADHD) in individuals with myelomeningocele. The rationale for the study was twofold: folate metabolizing genes, (e.g. MTHFR), are important not only in the etiology of neural tube defects but are also critical to cognitive function; and individuals with myelomeningocele have an elevated incidence of ADHD. Here, we tested 478 individuals with myelomeningocele for attention-deficit hyperactivity disorder behavior using the Swanson Nolan Achenbach Pelham-IV ADHD rating scale. Myelomeningocele participants in this group for whom DNAs were available were genotyped for seven single nucleotide polymorphisms (SNPs) in the MTHFR gene. The SNPs were evaluated for an association with manifestation of the ADHD phenotype in children with myelomeningocele. The data show that 28.7% of myelomeningocele participants exhibit rating scale elevations consistent with ADHD; of these 70.1% had scores consistent with the predominantly inattentive subtype. In addition, we also show a positive association between the SNP rs4846049 in the 3′-untranslated region of the MTHFR gene and the attention-deficit hyperactivity disorder phenotype in myelomeningocele participants. These results lend further support to the finding that behavior related to ADHD is more prevalent in patients with myelomeningocele than in the general population. These data also indicate the potential importance of the MTHFR gene in the etiology of the ADHD phenotype. 相似文献
9.
Gianluigi Mazzoccoli Mariangela Pia Dagostino Giulia Paroni Davide Seripa Filomena Ciccone Filomena Addante 《Chronobiology international》2017,34(8):1083-1093
Genome-wide association studies pinpointed common variants in or near the MTNR1B gene encoding MT2 melatonin receptor to be strongly associated with fasting glucose levels. IRS2 gene polymorphisms impact insulin resistance and epicardial fat (EF) thickness, which in turn is correlated with visceral adiposity, cognitive ability and risk for metabolic plus cardiovascular disease. We aimed to discover the interactions between MTNR1B and IRS2 gene polymorphisms, insulin sensitivity, EF thickness and cognitive performance in the elderly. In 60 subjects aged 60 years and older, we evaluated five single nucleotide polymorphisms (SNPs) within the MTNR1B locus (rs10830962, rs4753426, rs12804291, rs10830963, rs3781638), the Gly1057Asp variant of IRS2 gene (rs1805097), biochemical parameters, cognitive performance by the Mini Mental State Examination (MMSE) and EF thickness by transthoracic echocardiography. We found that MTNR1B and IRS2 gene variants impacted EF thickness, lipid profile and glucose homeostasis. IRS2 but not MTNR1B variants impacted MMSE scores. In conclusion, MTNR1B SNPs interact with IRS2 gene variant, correlate with the amount of epicardial adipose tissue and impact glucose homeostasis and lipid profile influencing cardiometabolic risk. 相似文献
10.
Katie A. Burren John M. Scott Andrew J. Copp Nicholas D. E. Greene 《Birth defects research. Part A, Clinical and molecular teratology》2010,88(2):76-83
BACKGROUND : Suboptimal maternal folate status is considered a risk factor for neural tube defects (NTDs). However, the relationship between dietary folate status and risk of NTDs appears complex, as experimentally induced folate deficiency is insufficient to cause NTDs in nonmutant mice. In contrast, folate deficiency can exacerbate the effect of an NTD‐causing mutation, as in splotch mice. The purpose of the present study was to determine whether folate deficiency can induce NTDs in mice with a permissive genetic background which do not normally exhibit defects. METHODS : Folate deficiency was induced in curly tail and genetically matched wild‐type mice, and we analyzed the effect on maternal folate status, embryonic growth and development, and frequency of NTDs. RESULTS : Folate‐deficient diets resulted in reduced maternal blood folate, elevated homocysteine, and a diminished embryonic folate content. Folate deficiency had a deleterious effect on reproductive success, resulting in smaller litter sizes and an increased rate of resorption. Notably, folate deficiency caused a similar‐sized, statistically significant increase in the frequency of cranial NTDs among both curly tail (Grhl3 mutant) embryos and background‐matched embryos that are wild type for Grhl3. The latter do not exhibit NTDs under normal dietary conditions. Maternal supplementation with myo‐inositol reduced the incidence of NTDs in the folate‐deficient wild‐type strain. CONCLUSIONS : Dietary folate deficiency can induce cranial NTDs in nonmutant mice with a permissive genetic background, a situation that likely parallels gene‐nutrient interactions in human NTDs. Our findings suggest that inositol supplementation may ameliorate NTDs resulting from insufficient dietary folate. Birth Defects Research (Part A), 2010. © 2009 Wiley‐Liss, Inc. 相似文献
11.
Eloualid A Abidi O Charif M El Houate B Benrahma H Louanjli N Chadli E Ajjemami M Barakat A Bashamboo A McElreavey K Rhaissi H Rouba H 《PloS one》2012,7(3):e34111
The methylenetetrahydrofolate reductase (MTHFR) gene is one of the main regulatory enzymes involved in folate metabolism, DNA synthesis and remethylation reactions. The influence of MTHFR variants on male infertility is not completely understood. The objective of this study was to analyze the distribution of the MTHFR C677T and A1298C variants using PCR-Restriction Fragment Length Polymorphism (RFLP) in a case group consisting of 344 men with unexplained reduced sperm counts compared to 617 ancestry-matched fertile or normozoospermic controls. The Chi square test was used to analyze the genotype distributions of MTHFR polymorphisms. Our data indicated a lack of association of the C677T variant with infertility. However, the homozygous (C/C) A1298C polymorphism of the MTHFR gene was present at a statistically high significance in severe oligozoospermia group compared with controls (OR = 3.372, 95% confidence interval CI = 1.27–8.238; p = 0.01431). The genotype distribution of the A1298C variants showed significant deviation from the expected Hardy-Weinberg equilibrium, suggesting that purifying selection may be acting on the 1298CC genotype. Further studies are necessary to determine the influence of the environment, especially the consumption of diet folate on sperm counts of men with different MTHFR variants. 相似文献
12.
Ibarrola-Villava M Fernandez LP Alonso S Boyano MD Peña-Chilet M Pita G Aviles JA Mayor M Gomez-Fernandez C Casado B Martin-Gonzalez M Izagirre N De la Rua C Asumendi A Perez-Yarza G Arroyo-Berdugo Y Boldo E Lozoya R Torrijos-Aguilar A Pitarch A Pitarch G Sanchez-Motilla JM Valcuende-Cavero F Tomas-Cabedo G Perez-Pastor G Diaz-Perez JL Gardeazabal J Martinez de Lizarduy I Sanchez-Diez A Valdes C Pizarro A Casado M Carretero G Botella-Estrada R Nagore E Lazaro P Lluch A Benitez J 《PloS one》2011,6(4):e19271
As the incidence of Malignant Melanoma (MM) reflects an interaction between skin colour and UV exposure, variations in genes implicated in pigmentation and tanning response to UV may be associated with susceptibility to MM. In this study, 363 SNPs in 65 gene regions belonging to the pigmentation pathway have been successfully genotyped using a SNP array. Five hundred and ninety MM cases and 507 controls were analyzed in a discovery phase I. Ten candidate SNPs based on a p-value threshold of 0.01 were identified. Two of them, rs35414 (SLC45A2) and rs2069398 (SILV/CKD2), were statistically significant after conservative Bonferroni correction. The best six SNPs were further tested in an independent Spanish series (624 MM cases and 789 controls). A novel SNP located on the SLC45A2 gene (rs35414) was found to be significantly associated with melanoma in both phase I and phase II (P<0.0001). None of the other five SNPs were replicated in this second phase of the study. However, three SNPs in TYR, SILV/CDK2 and ADAMTS20 genes (rs17793678, rs2069398 and rs1510521 respectively) had an overall p-value<0.05 when considering the whole DNA collection (1214 MM cases and 1296 controls). Both the SLC45A2 and the SILV/CDK2 variants behave as protective alleles, while the TYR and ADAMTS20 variants seem to function as risk alleles. Cumulative effects were detected when these four variants were considered together. Furthermore, individuals carrying two or more mutations in MC1R, a well-known low penetrance melanoma-predisposing gene, had a decreased MM risk if concurrently bearing the SLC45A2 protective variant. To our knowledge, this is the largest study on Spanish sporadic MM cases to date. 相似文献
13.
Hozyasz KK Mostowska A Szaflarska-Poplawska A Lianeri M Jagodzinski PP 《Molecular biology reports》2012,39(3):3123-3130
Celiac disease (CD) is a polygenic chronic enteropathy conferring an increased risk for various nutrient deficiency states.
Hyperhomocysteinemia is a frequent finding in CD and may be related to the development of venous thrombosis, cardiovascular
disease, and stroke in untreated CD patients. Recently, a possible excess in the frequency of the MTHFR c.677C>T (rs1801133) gene variant in CD patients was reported. The purpose of this study was to determine if there exist
differences in the distribution of polymorphic variants of genes involved in homocysteine/methyl group metabolism between
CD patients and the general population. A set of 10 gene polymorphisms (MTHFR rs1801133, MTR rs1805087, MTHFD1 rs2236225, MTRR rs1801394, CBS 844ins68, BHMT1 rs7356530 and rs3733890, BHMT2 rs526264 and rs625879, and TCN2 rs1801198) was tested in 134 patients with CD and 160 matched healthy controls. The frequency of the MTR rs1805087 GG genotype in CD patients was lower than in controls (0.01 and 0.06, respectively), although statistical significance
was not achieved (P = 0.06). For the other analyzed polymorphisms, there was no evidence of difference in both allelic and genotypic distribution
between cases and controls. The exhaustive Multifactor Dimensionality Reduction analysis revealed no combination of interactive
polymorphisms predicting the incidence of CD. In contrast to the well-documented clinical observations of increased risks
of vascular disease in patients with longstanding untreated CD, in our group of patients no significant association with CD
was found for all tested polymorphic variants of genes involved in homocysteine metabolism. These findings should be replicated
in studies with a larger sample size. 相似文献
14.
A. S. Weiner U. A. Boyarskih E. N. Voronina I. A. Selezneva T. V. Sinkina A. F. Lazarev V. D. Petrova M. L. Filipenko 《Molecular Biology》2010,44(5):720-727
Breast cancer is one of the most widely distributed cancers in women. We investigated the role of allele variants in the folate
metabolizing genes MTHFR (C677T and A1298C alleles), SHMT1 (C1420T allele), and MTHFD (G1258A allele) as a possible factor in predisposition to breast cancer. We determined allele and genotype frequencies of
single nucleotide polymorphisms (SNPs) in the case (850 women with sporadic form of breast cancer) and control (810 healthy
women) groups. None of the polymorphisms were significantly associated with breast cancer risk. To increase the statistical
power of our study, we conducted a meta-analysis which included published genotype data and the results of our work. The meta-analysis
revealed no significant association between the studied SNPs and breast cancer risks either. 相似文献
15.
Shi M Caprau D Romitti P Christensen K Murray JC 《Birth defects research. Part A, Clinical and molecular teratology》2003,67(8):545-549
BACKGROUND
Genetic variation in enzymes involved in vitamin metabolism is a candidate for analysis in studies of how nutritional covariates may impact a disease state. The role of folate pathway genes in birth defects and cardiovascular disease in humans has been widely studied. Since incidence rates for these disorders vary by geographic origins, it is useful to know which variants are the best candidates for studies based on genotype and allele frequency, as well as linkage disequilibrium (LD) in founder populations.METHODS
Six polymorphisms in five folate metabolism‐related genes (MTHFR, MTHFD, MTRR, GCP2, and RFC1) were genotyped on a collection of 1064 DNA samples from populations around the world, which were made available by the Centre d'Étude du Polymorphisme Humain (CEPH) consortium for analysis.RESULTS
In this study we report the genotype frequencies for variants in the MTHFR, MTHFD, MTRR, GCP2, and RFC1 genes, and the LD for two variants (C677T and A1298C) in MTHFR.CONCLUSIONS
The rare allele frequency for each of the five genes studied varied widely. LD is strongest in Pakistani and Brazilian populations (D′ = 1.0) and weakest in Mexican populations (D′ = 0.45). These findings will allow the selection of variants that will provide the most power in studies of folate pathway genes involving different ancestral populations, and contribute to our knowledge of the population distribution of selected nutritional gene variants. Birth Defects Research (Part A), 2003. © 2003 Wiley‐Liss, Inc.16.
Nezha Senhaji Nadia Serbati Brehima Diakité Sofia Arazzakou Khalil Hamzi Wafaa Badre Sellama Nadifi 《Gene》2013
Background
The association of genetic polymorphisms related to metabolism of homocysteine and folate with inflammatory bowel disease has been evidenced. Several studies have identified genetic variants of MTHFR as significant susceptibility loci for Crohn's disease (CD) and ulcerative colitis (UC). The C677T genetic polymorphism in the MTHFR gene is found to be associated with a thermolabile variant enzyme that shows a reduced activity. Therefore, we investigated whether the C677T variant confers genetic susceptibility to CD or UC and evaluated the genotype–phenotype associations in the Moroccan population.Methods
The present study included 96 inflammatory bowel disease patients (68 patients with CD and 28 with UC) and 182 healthy controls. DNA samples were genotyped for the MTHFR (C677T) mutation by the PCR-RFLP method. Statistical analyzes were performed using MedCalc software, Chi square test and Fisher test.Results
The respective odds ratio for CD, UC and control group were, 1.55 (CI 95%: 0.53–4.53, P = 0.52); 0.50 (CI 95%: 0.06–4.15, P = 0.52) and 0.50 (CI 95%: 0.06–4.15, P = 0.52). Thus, no statistically significant association with the disease was observed in frequency of the TT variant in comparison to healthy controls. Stratification of IBD patients on the basis of CD or UC showed that individuals carrying at least one T allele are not protected against Crohn's disease. Furthermore, clinical features of the disease did not show any significant association.Conclusion
In conclusion, the present study indicates that the genetic risk for IBD is not modulated by MTHFR C677T polymorphism in Moroccan population. 相似文献17.
Maria G. Kakkoura Christiana A. Demetriou Maria A. Loizidou Giorgos Loucaides Ioanna Neophytou Yiola Marcou Andreas Hadjisavvas Kyriacos Kyriacou 《Genes & nutrition》2015,10(2)
Single-nucleotide polymorphisms (SNPs) within genes of the one-carbon metabolism pathway have been shown to interact with dietary folate intake to modify breast cancer (BC) risk. Our group has previously demonstrated that the Mediterranean dietary pattern, rich in beneficial one-carbon metabolism micronutrients, protects against BC in Greek-Cypriot women. We aimed to investigate whether SNPs in the MTHFR (rs1801133 and rs1801131) and MTR (rs1805087) genes modify the effect of the Mediterranean dietary pattern on BC risk. Dietary intake data were obtained using a 32-item food-frequency questionnaire. A dietary pattern specific to the Greek-Cypriot population, which closely resembles the Mediterranean diet, was derived using principal component analysis (PCA) and used as our dietary variable. Genotyping was performed on subjects from the MASTOS study, a case–control study of BC in Cyprus, using TaqMan assays. Adjusted odds ratios (ORs) were estimated using logistic regression analyses. High adherence to the PCA-derived Mediterranean dietary pattern further reduced BC risk with increasing number of variant MTHFR 677T alleles (ORQ4vs.Q1 for 677TT = 0.37, 95 % CI 0.20–0.69, for 677 CT = 0.60, 95 % CI 0.42–0.86). Additionally, high adherence to the Mediterranean dietary pattern decreased BC risk in subjects with at least one MTR 2756A allele (ORQ4vs.Q1 for 2756AA = 0.59, 95 % CI 0.43–0.81, for 2756AG = 0.59, 95 % CI 0.39–0.91) and in subjects with the MTHFR 1298CC genotype (ORQ4vs.Q1 0.44, 95 % CI 0.30–0.65). Overall P-interaction values, however, were not statistically significant. Our study suggests that these MTHFR and MTR SNPs may act as effect modifiers, highlighting their biological significance in the association between Mediterranean diet, the one-carbon metabolism pathway and BC.
Electronic supplementary material
The online version of this article (doi:10.1007/s12263-015-0453-7) contains supplementary material, which is available to authorized users. 相似文献18.
Jenil Patel Emine Bircan Xinyu Tang Mohammed Orloff Charlotte A. Hobbs Marilyn L. Browne Lorenzo D. Botto Richard H. Finnell Mary M. Jenkins Andrew Olshan Paul A. Romitti Gary M. Shaw Martha M. Werler Jingyun Li Wendy N. Nembhard the National Birth Defects Prevention Study 《PLoS genetics》2021,17(3)
Previous research on risk factors for obstructive heart defects (OHDs) focused on maternal and infant genetic variants, prenatal environmental exposures, and their potential interaction effects. Less is known about the role of paternal genetic variants or environmental exposures and risk of OHDs. We examined parent-of-origin effects in transmission of alleles in the folate, homocysteine, or transsulfuration pathway genes on OHD occurrence in offspring. We used data on 569 families of liveborn infants with OHDs born between October 1997 and August 2008 from the National Birth Defects Prevention Study to conduct a family-based case-only study. Maternal, paternal, and infant DNA were genotyped using an Illumina Golden Gate custom single nucleotide polymorphism (SNP) panel. Relative risks (RR), 95% confidence interval (CI), and likelihood ratio tests from log-linear models were used to estimate the parent-of-origin effect of 877 SNPs in 60 candidate genes in the folate, homocysteine, and transsulfuration pathways on the risk of OHDs. Bonferroni correction was applied for multiple testing. We identified 3 SNPs in the transsulfuration pathway and 1 SNP in the folate pathway that were statistically significant after Bonferroni correction. Among infants who inherited paternally-derived copies of the G allele for rs6812588 in the RFC1 gene, the G allele for rs1762430 in the MGMT gene, and the A allele for rs9296695 and rs4712023 in the GSTA3 gene, RRs for OHD were 0.11 (95% CI: 0.04, 0.29, P = 9.16x10-7), 0.30 (95% CI: 0.17, 0.53, P = 9.80x10-6), 0.34 (95% CI: 0.20, 0.57, P = 2.28x10-5), and 0.34 (95% CI: 0.20, 0.58, P = 3.77x10-5), respectively, compared to infants who inherited maternally-derived copies of the same alleles. We observed statistically significant decreased risk of OHDs among infants who inherited paternal gene variants involved in folate and transsulfuration pathways. 相似文献
19.
Adrianna Mostowska Kamil K. Hozyasz Piotr Wójcicki Agnieszka Lasota Izabella Dunin‐Wilczyńska Paweł P. Jagodziński 《Birth defects research. Part A, Clinical and molecular teratology》2012,94(11):943-950
BACKGROUND: Nonsyndromic cleft lip with or without cleft palate (NSCL/P) is one of the most common congenital anomalies, with a complex and still not fully understood etiology. Given the important role of the Wnt/β‐catenin pathway during craniofacial development, we decided to test the hypothesis that common polymorphic variants of the genes encoding crucial components of this signaling pathway might contribute to the risk of NSCL/P in the Polish population. METHODS: A set of 19 single nucleotide polymorphisms (SNPs) in the APC, AXIN1, AXIN2, CTNNB1, DVL2, and GSK‐3β genes were analyzed using restriction fragment length polymorphism and high‐resolution melting curve methods in a group of 280 patients with NSCL/P and a properly matched control group (n = 330). RESULTS: Both single‐marker and haplotype analyses showed an association between SNPs in the DVL2 gene and the risk for NSCL/P. The strongest association was found under an overdominant model for the rs35594616 variant located in the exonic sequence of DVL2 (odds ratio [OR], 1.90; 95% confidence interval [CI], 1.37–2.62; p < 0.0001). Moreover, the gene‐gene interaction analysis revealed a significant epistatic interaction between DVL2 gene SNPs in the susceptibility to orofacial clefts. Borderline association with a decreased risk of NSCL/P was also observed for the AXIN2 rs3923087 variant (dominant model OR, 0.69; 95% CI, 0.50–0.95; p = 0.03). CONCLUSION: This study suggests that polymorphic variants of the Wnt/β‐catenin pathway genes have a role in the susceptibility to orofacial clefts. The DVL2 and AXIN2 genes might be candidate genes for this craniofacial anomaly in the Polish population. Birth Defects Research (Part A), 2012. © 2012 Wiley Periodicals, Inc. 相似文献
20.
Study on Environmental Causes and SNPs of MTHFR,MS and CBS Genes Related to Congenital Heart Disease
Hui Shi Shiwei Yang Yan Liu Peng Huang Ning Lin Xiaoru Sun Rongbin Yu Yuanyuan Zhang Yuming Qin Lijuan Wang 《PloS one》2015,10(6)