Evaluation of C677T polymorphism of the methylenetetra hydrofolate reductase gene and its association with levels of serum homocysteine, folate, and vitamin B12 as maternal risk factors for Down syndrome

Abstract

AIMS AND OBJECTIVE:Evaluation of C677T polymorphisms of the methylenetetra hydrofolate reductase (MTHFR) gene and its association with level of serum homocysteine, folate, and vitamin B12 as possible maternal risk factors for Down syndrome.DESIGN:This was a case–control study.MATERIAL AND METHODSFifty-two mothers (mean age 27.6 years) with babies having free trisomy 21 of North Indian ethnicity and 52 control nonlactating mothers (mean age 24.9 years) of same ethnicity attending services of genetic lab for bloodletting for other causes were enrolled after informed written consent. Fasting blood was collected and was used for determination of plasma homocysteine, vitamin B12, and folate (serum and RBC), and for PCR amplification of the MTHFR gene.RESULTS:The prevalence of MTHFR C677T polymorphism in north Indian mothers of babies with trisomy 21 Down syndrome was 15.38% compared to 5.88 % in controls. The difference between two groups was not statistically significant (P = 0.124). Low serum folate was demonstrated in 34.62% of cases vs. 11.54% in controls, which was significant (P = 0.005). Low RBC folate was found in 30.7% of cases versus 11.53% in controls, which was not significant (P = 0.059), when analyzed independently. But on multiple regression analysis the difference was statistically significant. Low serum vitamin B12 was found in 42.31% of cases versus 34.62% in controls, which was not significant (P = 0.118). The mean serum homocysteine in cases was 10.35 ± 0.68 while controls were 9.02 ± 0.535.CONCLUSION:Serum levels of folate were low in cases. The RBC folate levels were comparable in both groups. However the combined serum folate and RBC folate were low in cases compared to control groups. Homocysteine levels in our study were higher in Down syndrome mothers compared to controls; however high-serum level of Homocysteine had no association with MTHFR polymorphism. No association of serum vitamin B12 with MTHFR polymorphism in occurrence of Down syndrome births was found. Peri- or preconceptional folate supplementation may therefore lead to a decline in DS births, if supported by larger studies.

Evaluation of C677T Polymorphism of the Methylenetetrahydrofolate Reductase (MTHFR) Gene in various Neurological Disorders

“…Various studies have shown that the C677T polymorphism is a maternal risk factor for DS [40][41][42][43][44]. However, there are few studies in patients with DS per se, as has been evaluated in our present study.…”

MTHFR gene polymorphism and associated nutritional deficiency in the etiology and pathogenesis of Down syndrome

“…Afterwards, numbers of studies were conducted in different regions of the world with a lot of variation in the results [9,11]. Some studies on MTHFR polymorphism have been conducted in India also and have shown variation in results which could be due to differences in geographical regions [12,13]. The present study showed that the distribution of MTHFR C677T polymorphisms was significantly higher in the DSM group when compared to the CM group.…”

“…The T allele was observed to be higher in DSM and lower in CM and no individual showed T/T genotype in both the groups. Some other Indian studies of different regions also did not observe T/T genotype in DSM [7,12], while few studies found T/T genotype in DSM in very low frequency [14,15]. These results suggest that the distribution of T/T genotype is lower in the Indian population.…”

Association of maternal folate with methylene tetrahydrofolate reductase polymorphism relationship in infants <3 months with Down syndrome

“…[1] We found a genuine relationship between maternal folate and MTHFR gene polymorphism in <3 months infants, which was not analyzed in the original article. In DS mothers with baby <3 months, red blood cell (RBC) folate were significantly lower than controls, but not in case of serum folate.…”