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

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 METHODS Fifty-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.

[1]  P. Hunt,et al.  Lack of Checkpoint Control at the Metaphase/Anaphase Transition: A Mechanism of Meiotic Nondisjunction in Mammalian Females , 1997, The Journal of cell biology.

[2]  M. Zago,et al.  Analysis of the 677 C→T Mutation of the Methylenetetrahydrofolate Reductase Gene in Different Ethnic Groups , 1998, Thrombosis and Haemostasis.

[3]  R. Rozen,et al.  Polymorphisms in genes involved in folate metabolism as maternal risk factors for Down syndrome. , 2000, American journal of human genetics.

[4]  A. Parle‐McDermott,et al.  MTRR and MTHFR polymorphism: link to Down syndrome? , 2002, American journal of medical genetics.

[5]  V. Gatta,et al.  C677T mutation in the 5,10-MTHFR gene and risk of Down syndrome in Italy , 2002, European Journal of Human Genetics.

[6]  F. Sheth,et al.  Gene polymorphism and folate metabolism: a maternal risk factor for Down syndrome. , 2003, Indian pediatrics.

[7]  Trygve O Tollefsbol,et al.  The impact of metabolism on DNA methylation. , 2005, Human molecular genetics.

[8]  Helen V. Firth,et al.  Down syndrome (trisomy 21) , 2005 .

[9]  S. Singh,et al.  Mutation C677T in the methylenetetrahydrofolate reductase gene is associated with male infertility in an Indian population. , 2005, International journal of andrology.

[10]  D. Brunoni,et al.  Relationship between polymorphisms in genes involved in homocysteine metabolism and maternal risk for Down syndrome in Brazil , 2005, American journal of medical genetics. Part A.

[11]  V. Ganji,et al.  Trends in serum folate, RBC folate, and circulating total homocysteine concentrations in the United States: analysis of data from National Health and Nutrition Examination Surveys, 1988-1994, 1999-2000, and 2001-2002. , 2006, The Journal of nutrition.

[12]  R. Raman,et al.  MTHFR C677T and A1298C polymorphisms are risk factors for Down's syndrome in Indian mothers , 2006, Journal of Human Genetics.

[13]  R. Pandey,et al.  Prevalence of MTHFR C677T polymorphism in north Indian mothers having babies with Trisomy 21 Down syndrome. , 2008, Down's syndrome, research and practice : the journal of the Sarah Duffen Centre.

[14]  M. Eberlin,et al.  Genetic polymorphisms involved in folate metabolism and elevated plasma concentrations of homocysteine: maternal risk factors for Down syndrome in Brazil. , 2008, Genetics and molecular research : GMR.

[15]  K. Satyamoorthy,et al.  MTHFR Gene variants C677T, A1298C and association with Down syndrome: A Case-control study from South India , 2009, Indian journal of human genetics.