Congenital heart defects and hypothyroidism in Down syndrome patients with common MTHFR polymorphisms

Abstract

MTHFR is an essential enzyme in the folate pathway. Down syndrome (DS), which affects 1 in 700 live births, is common chromosomal aneuploidy with documented dysregulation in cellular folate pathway. Homocysteine accumulation is caused by dysregulation in MTHFR activity and hyperhomocysteinemia is a stand-alone risk factor for a number of vascular diseases. There is an association between the MTHFR polymorphisms C677T and A1298C with stroke, thromboembolism, and hypothyroidism. Patients with Down syndrome frequently have a variety of co-morbidities, including intellectual disability, congenital heart defects, gastrointestinal problems including celiac disease, thyroid disease, and early Alzheimer disease,. However, no comprehensive study has been conducted to ascertain whether how MTHFR polymorphisms, homocysteine, and cysteine levels are correlated to different co-morbidities in Down syndrome. Therefore, in this study, we examined common polymorphisms in the MTHFR gene as well as the levels of cysteine and homocysteine in DS patients with various comorbidities and found that MTHFR C677T and MTHFR A1298C are over-represented in DS patients than in controls. Also MTHFRC677T is linked to hypothyroidism in DS patients, while MTHFR AA1298AC and MTHFRAA1298CC are linked to both hypothyroidism and CHD in DS patients. Hence this study would enable better prognostication and counseling for DS children and appropriate monitoring and follow up.