MTRR and MTHFR polymorphism: Link to Down syndrome?

O’Leary, Valerie B.; Parle‐McDermott, Anne; Molloy, Anne M.; Kirke, Peadar N.; Johnson, Z.; Conley, Mary; Scott, John M.; Mills, James L.

doi:10.1002/ajmg.10121

Cited by 163 publications

(131 citation statements)

References 11 publications

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“…The present study demonstrates the association of both C677T and A1298C SNPs with mothers of DS children and a correlation with the mother's age in an Indian population. However, various other studies did not find a similar association with DS mothers (Petersen et al 2000;O'Leary et al 2002;Chadefaux-Vekemans et al 2002;Boduroglu et al 2004;Chango et al 2005;Da Silva et al 2005). Da Silva et al (2005) have shown a higher frequency of the 677T allele and elevated homocysteine levels in mothers with DS children, but consider it a minor predisposing risk factor for DS.…”

Section: A1298cmentioning

confidence: 90%

“…They also showed that a SNP in another gene associated with methionine-homocysteine metabolism, methionine synthase reductase (MTRR, OMIM*602568; chromosome 5p15.2-.3), also has an association with case mothers (with DS children). However, subsequent studies from different populations from Europe, the USA and Turkey have produced a mixed picture, finding no association with MTHFR C677T and showing either no or weak association with MTRR and another MTHFR SNP, A1298C (Chadefaux-Vekemans et al 2002;O'Leary et al 2002;Boduroglu et al 2004). …”

Section: Introductionmentioning

confidence: 99%

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MTHFR C677T and A1298C polymorphisms are risk factors for Down’s syndrome in Indian mothers

Kumar

Singh

Mehta³

et al. 2006

J Hum Genet

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Down's syndrome (DS), a chromosomal disorder due to trisomy 21, results mostly from nondisjunction in maternal meiosis. The present case-control study examined the association of genetic polymorphisms with predisposition to nondisjunction. Two common polymorphisms (SNPs), C677T and A1298C, in the 5,10-methylenetetrahydrofolate reductase (MTHFR) gene involved in folate metabolism, are known to lower the activity of this enzyme. Three hundred and fourteen mothers (with DS children and controls), mostly from the eastern states of India, were genotyped for the two above-mentioned SNPs. Significant association with both of these SNPs were detected, more specifically, in the mothers of DS children homozygous for the polymorphic alleles 677 T and 1298 C. The relative risk of T (C677T) and C (A1298C) homozygosity in mothers for DS-affected pregnancy was 7 (OR 7.67, 95% CI 1.67-35.08, P=0.003) and 4 (OR 4.40, 95% CI 1.45-13.26, P=0.008), respectively. Moreover, all 677TT mothers studied were less than 31 years of age, whereas no correlation with maternal age was observed for A1298C genotypes. Interestingly, all of the young 677TT mothers had either a first-or secondborn child with DS. Thus, this study reports that young Indian mothers with TT genotypes are genetically predisposed to nondisjunction due to abnormal folate metabolism.

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Section: A1298cmentioning

confidence: 90%

Section: Introductionmentioning

confidence: 99%

MTHFR C677T and A1298C polymorphisms are risk factors for Down’s syndrome in Indian mothers

Kumar

Singh

Mehta³

et al. 2006

J Hum Genet

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“…Figure 1 presents a flow chart of the retrieved studies and the studies excluded, with specifying reasons. Eleven studies dealt with MTHFR C677T (James et al 1999;Hobbs et al 2000;Stuppia et al 2002;O'Leary et al 2002;Boduroglu et al 2004;Acacio et al 2005;Chango et al 2005;da Silva et al 2005;Rai et al 2006;Scala et al 2006;Coppede et al 2006), seven with MTHFR A1298C (Boduroglu et al 2004;Acacio et al 2005;Chango et al 2005;da Silva et al 2005;Rai et al 2006;Scala et al 2006;Coppede et al 2006), and five with MTRR A66G (Hobbs et al 2000;O'Leary et al 2002;Chango et al 2005;da Silva et al 2005;Scala et al 2006). The studies that investigated MTHFR A1298C or MTRR A66G also investigated MTHFR C677T.…”

Section: Eligible Studiesmentioning

confidence: 99%

“…Studies were conducted in various populations of different ''racial'' groups: seven involved whites (Coppede et al 2006;Chango et al 2005;O'Leary et al 2002;Scala et al 2006;Stuppia et al 2002;Hobbs et al 2000;James et al 1999), two mixed Brazilians (da Silva et al 2005;Acacio et al 2005), one Indian (Rai et al 2006), and one Turkish (Boduroglu et al 2004). A list of the details abstracted from the studies included in the meta-analysis is provided in Table 1.…”

Section: Eligible Studiesmentioning

confidence: 99%

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Maternal gene polymorphisms involved in folate metabolism and risk of Down syndrome offspring: a meta-analysis

Ζιντζαράς

2007

J Hum Genet

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Studies investigating the association between gene polymorphisms involved in homocysteine/folate metabolism and Down syndrome (DS) have reported contradictory or inconclusive results. A meta-analysis of 11 case-control studies relating MTHFR C677T, MTHFR A1298C and MTRR A66G gene polymorphisms to the maternal risk of DS was carried out. For MTHFR C677T polymorphism the heterogeneity between studies was significant (P = 0.03) and the random effects (RE) pooled odds ratio (OR) was not significant: RE OR = 1.18 (0.99-1.40). The recessive model for allele MTHFR 677T showed nonsignificant heterogeneity overall (P = 0.21) and the association was not significant: fixed effects (FE) OR = 1.27 (0.98-1.64). However, sensitivity analysis changed the pattern of results and the association became marginally significant [FE OR = 1.31 (1.01-1.71)]. The dominant model showed no association. Finally, statistically significant associations between the MTHFR A1298C and MTRR A66G gene polymorphisms and the risk of DS were not found. The cumulative meta-analysis of MTHFR C677T showed a trend toward an association as the amount of data increased, and the recursive cumulative metaanalysis indicated that there was insufficient evidence for claiming or denying an association for all gene polymorphisms. In addition, there was no difference between the magnitude of effect observed in large versus small studies. Large and rigorous case-control studies that investigate gene-gene and gene-environment interactions need to be performed before conclusive claims about the genetics of DS can be made.

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Effects of UV Photographs, Photoaging Information, and Use of Sunless Tanning Lotion on Sun Protection Behaviors

Williams¹,

Mars²,

Buyske³

et al. 2005

Arch Dermatol

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MTRR and MTHFR polymorphism: Link to Down syndrome?

Cited by 163 publications

References 11 publications

MTHFR C677T and A1298C polymorphisms are risk factors for Down’s syndrome in Indian mothers

MTHFR C677T and A1298C polymorphisms are risk factors for Down’s syndrome in Indian mothers

Maternal gene polymorphisms involved in folate metabolism and risk of Down syndrome offspring: a meta-analysis

Effects of UV Photographs, Photoaging Information, and Use of Sunless Tanning Lotion on Sun Protection Behaviors

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