Maternal association and influence of DHFR 19 bp deletion variant predisposes foetus to anencephaly susceptibility: a family-based triad study

Abstract

Objective: Previous studies have not used family-based methods to evaluate maternal-paternal genetic effects of the folate metabolizing enzyme, dihydro folate reductase (DHFR) essential during embryogenesis. Present study focuses on evaluating the association and influence of parental genetic effects of DHFR 19 bp deletion in the development of foetal neural tube defects (NTDs) using family-based triad approach.

Materials and methods: The study population (n = 924) including 124 NTD case-parent trios (n = 124 × 3 = 372) and 184 healthy control-parent trios (n = 184 × 3 = 552) from Telangana, India, was genotyped for DHFR 19 bp deletion. Statistical analysis was used by SPSS and parent-of-origin effects (POE).

Results: Foetuses with deletion genotype (DD) were at risk of developing anencephaly (OR = 3.26, p = 0.020). Among parents, increased maternal risk of having an anencephaly foetus (OR = 2.66, p = 0.028) was observed in mothers with DD genotype. In addition, POE analysis also demonstrated higher risk of maternal transmission of the deletion allele to anencephaly foetus compared with paternal transmission (OR = 6.00, p = 0.016). Interestingly, maternal-paternal-offspring genotype incompatibility revealed maternal deletion genotype (DD) in association with paternal heterozygous deletion genotype (WD) significantly increased risk for NTDs (OR = 5.29, p = 0.013).

Conclusions: This study, using family-based case-parent and control-parent triad approach, is the first to report influence of maternal transmission of DHFR 19 bp deletion in the development of anencephaly in the foetus.

Keywords:

• Neural tube defects
• DHFR
• anencephaly
• family-based triad study
• transmission disequilibrium
• parent-of-origin effects

Acknowledgements

The authors gratefully acknowledge Department of Biotechnology, New Delhi, India, for providing facilities. The authors would like to thank Sanjay Kumar Jadhav for technical assistance in performing ELISA.

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

The authors gratefully acknowledge Indian Council of Medical Research (ICMR), New Delhi, India (45/7/2014-HUMBMS) and UGC-Non NET, New Delhi for providing Research Fellowship to K.R. Prasoona.