Folate and homocysteine levels predict Down Syndrome births by Carolyn Ledowsky
While older women know that their babies have a higher chance of developing Down syndrome (DS), most DS children are born to young mothers – indicating that other factors are involved. The MTHFR C677T mutation was first implicated way back in 1999, when one study theorized that the variant could cause different patterns of DNA methylation that might affect cell division. Similar studies conducted since then on different populations have yielded conflicting results, and the jury is still out.
It’s possible that a combination of multiple genetic variants could compound the risk, or that genetics combines with environmental factors such as homocysteine (Hcy) levels and the mother’s nutrient concentrations to affect pregnancy outcomes. So far, the medical community has been slow to investigate these issues.
To shed more light on the causes of DS, a new study published in the journal Human Reproduction looked at both gene-gene interactions and gene-environment interactions among DS parents and children. They evaluated 151 Down syndrome children, most of whom were born to young parents in their twenties, as well as the parents themselves. They compared the DS families to 200 healthy children of the same ages, as well as their parents.
Specifically, the authors examined six mutations in five genes of the Hcy metabolic pathway, including:
SLC19A1
127 RFC1 (G80A)
MTHFR (C677T & A1298C)
MTR (A2756G)
TCN2 (C776G)
CBS (844ins68 bp)
They also measured concentrations of Hcy, cysteine, vitamin B12, and folate.
Interestingly, roughly 92% of the DS mothers had a history of spontaneous abortion, as opposed to 32% in control mothers. Most of the miscarriages occurred in the first trimester. DS mothers also had a much higher frequency of the T allele of MTHFR C677T mutations, as compared with the healthy controls. The MTHFR A1298C variant was somewhat higher in DS mothers, but the difference wasn’t statistically significant. But altogether, MTHFR mutations (C677T & A1298C) were much higher in DS mothers. 56% of DS mothers had four or more of the genetic variants tested, as compared with only 11% of the control mothers. The combinations appeared to be particularly potent when they involved MTHFR mutations.
The DS children themselves were more significantly more likely to be male, have elevated cysteine levels, and low levels of vit-B12 and folate. They were also more likely to have a MTHFR C677T mutations and SLC19A1 G80A mutations.
The nutritional findings were particularly significant when it came to DS fathers. While the genes of these men weren’t associated with child status, DS fathers did have significantly elevated levels of Hcy, as well as low levels of B12 and folate. Overall, 70% of DS parents were deficient in vit-B12, and 35% had a folate deficiency. DS children had lower Hcy levels than both their parents and the control children. They also had low levels of vitamin B12 and folate.
The key takeaway is that you’re pregnant or trying to conceive, be sure to be tested for genetic mutations, even if you’re young. Getting a head start on nutritional supplements and antenatal care, particularly during preconception, can reduce the risk of this disease.
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