Paternal transmission of MTHFD1 G1958A variant predisposes to neural tube defects in the offspring

• Published in: Developmental medicine and child neurology 2016-06, Vol.58 (6), p.625-631
• Main Authors: Prasoona, Kattekola R, Sunitha, Tella, Srinadh, Buragadda, Deepika, Madireddy L N, Kumari, Tiruvatturu M, Jyothy, Akka
• Format: Article
• Language: English
• Subjects: Adult; Case-Control Studies; Female; Genetic Predisposition to Disease; Humans; India; Infant, Newborn; Infant, Newborn, Diseases - genetics; Male; Methylenetetrahydrofolate Dehydrogenase (NADP) - genetics; Minor Histocompatibility Antigens - genetics; Neural Tube Defects - genetics; Paternal Inheritance
• ISSN: 0012-1622; 1469-8749
• DOI: 10.1111/dmcn.12929

Aim This study aimed to evaluate the role of methylenetetrahydrofolate dehydrogenase (MTHFD1) G1958A variant (rs2236225) as a ‘maternal, paternal, or embryonic’ genetic risk factor for neural tube defect (NTD) susceptibility. It also estimated differential associations based on type of NTD, offspring sex, maternal–paternal–offspring genotype incompatibility, and parent‐of‐origin effects (POE) using both case–control and family‐based approach. In addition, genotype impact on serum folate levels was also assessed. Method The study population (n=900) consisted of 120 NTD case‐parent triads (n=120×3=360) and 180 healthy control‐parent triads (n=180×3=540) from South India. Umbilical cord tissues were collected from those with NTD and control newborn infants, and blood samples from case and control parents. Genotyping was performed by polymerase chain reaction–restriction fragment length polymorphism. Statistical analysis used were SPSS, transmission disequilibrium test and POE. Serum folate levels were estimated using enzyme‐linked immunosorbent assay. Results In the case–control study, those with the MTHFD1 G1958A variant were associated with around twofold risk of anencephaly (p=0.01) and spina bifida (p