Metabolic Brain Disease

, Volume 33, Issue 4, pp 1343–1352 | Cite as

LRP2 gene variants and their haplotypes strongly influence the risk of developing neural tube defects in the fetus: a family-triad study from South India

  • Rebekah Prasoona K.
  • Sunitha T.
  • Srinadh B.
  • Muni Kumari T.
  • Jyothy A.
Original Article


Neural tube defects (NTDs) are the leading cause of infant deaths worldwide. Lipoprotein related receptor 2 (LRP2) has been shown to play a crucial role in neural tube development in mouse models. However, the role of LRP2 gene in the development of human NTDs is not yet known. In view of this, family-based triad approach has been followed considering 924 subjects comprising 124 NTD case-parent trios and 184 control-parent trios diagnosed at Institute of Genetics and Hospital for Genetic Diseases, Hyderabad. Blood and tissue samples were genotyped for rs3755166 (−G759A) and rs2544390 (C835T) variants of LRP2 gene for their association with NTDs. Assessment of maternal-paternal genotype incompatibility risk for NTD revealed 3.77-folds risk with a combination of maternal GA and paternal GG genotypes (GAxGG = GA,p < 0.001), while CT genotypes of both the parents showed 4.19-folds risk for NTDs (CTxCT = CT,p = 0.009). Haplotype analysis revealed significant risk of maternal A-T (OR = 4.48,p < 0.001) and paternal G-T haplotypes (OR = 5.22,p < 0.001) for NTD development. Further, linkage analysis for parent-of-origin effects (POE) also revealed significant transmission of maternal ‘A’ allele (OR = 2.33,p = 0.028) and paternal ‘T’ allele (OR = 6.00,p = 0.016) to NTDs. Analysis of serum folate and active-B12 levels revealed significant association with LRP2 gene variants in the causation of NTDs. In conclusion, the present family-based triad study provides the first report on association of LRP2 gene variants with human NTDs.


Humans Mice Animals Alleles Haplotypes Infant Deaths Neural Tube Defects Genotype Lipoproteins Folic Acid B12 



Indian Council of Medical Research (ICMR), New Delhi, India is gratefully acknowledged for providing Research Fellowship to Ms. K.R. Prasoona. Department of Biotechnology, New Delhi, India is deeply acknowledged for establishing lab facilities. Authors thank Mr. Sanjay Kumar Jadhav for his technical assistance.

Compliance with ethical standards

Conflict of interest

All the authors declare that there is no conflict of interest.


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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Institute of Genetics and Hospital for Genetic DiseasesOsmania UniversityHyderabadIndia
  2. 2.Modern Government Maternity HospitalHyderabadIndia

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