31 for 21: New Study on Folate Metabolism in Down Syndrome

It's been months since I read a study on Down syndrome, but the subject of folate metabolism and hte CBS gene always catches my eye. I have plenty of articles stored away to look at, just haven't taken the time to read them.


The study below was just published this month - October.

This study looks at genetic polymorphisms on the folate pathway. There are multiple genetic polymorphisms involved in Down syndrome - CBS & MTHFR to name a couple.  These cause problems in Homocysteine (Hcy), SAH (S-adenosylhomocysteine), SAM (S-adenosylmethionine), B12 and folate levels. You can see the full text of the study at the link below.

 I've blogged about this quite a bit on here. If you just search on the side of the blog for "folate", "homocysteine", "cbs gene", "SAM", etc, you'll find related blogs about it.

Genetic polymorphisms modulate the folate metabolism of Brazilian individuals with Down syndrome.

Abstract

Individuals with Down syndrome (DS) carry three copies of the Cystathionine β-synthase (CβS) gene. The increase in the dosage of this gene results in an altered profile of metabolites involved in the folate pathway, including reduced homocysteine (Hcy), methionine, S-adenosylhomocysteine (SAH) and S-adenosylmethionine (SAM). Furthermore, previous studies in individuals with DS have shown that genetic variants in genes involved in the folate pathway influence the concentrations of this metabolism's products. The purpose of this study is to investigate whether polymorphisms in genes involved in folate metabolism affect the plasma concentrations of Hcy and methylmalonic acid (MMA) along with the concentration of serum folate in individuals with DS. Twelve genetic polymorphisms were investigated in 90 individuals with DS (median age 1.29 years, range 0.07-30.35 years; 49 male and 41 female). Genotyping for the polymorphisms was performed either by polymerase chain reaction (PCR) based techniques or by direct sequencing. Plasma concentrations of Hcy and MMA were measured by liquid chromatography-tandem mass spectrometry as previously described, and serum folate was quantified using a competitive immunoassay. Our results indicate that the MTHFR C677T, MTR A2756G, TC2 C776G and BHMT G742A polymorphisms along with MMA concentration are predictors of Hcy concentration. They also show that age and Hcy concentration are predictors of MMA concentration. These findings could help to understand how genetic variation impacts folate metabolism and what metabolic consequences these variants have in individuals with trisomy 21.
PMID:

22903356

[PubMed - in process]

I thought I would close with this quote from the Discussion section of the full text:

In conclusion, our results indicate that the MTHFR C677T, MTR A2756G, TC2 C776G and BHMT G742A polymorphisms along with MMA concentration are predictors of Hcy concentration. They also show that age and Hcy concentration are predictors of MMA concentration. These findings could help to understand how genetic variation impacts folate metabolism and what metabolic consequences these variants have in individuals with trisomy 21.

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