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Recurrent early pregnancy loss and endothelial nitric oxide synthase gene polymorphisms

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Abstract

Objective(s): Studies on the relation between endothelial nitric oxide synthase (eNOS) activity in implantation and maintenance of pregnancy highlights the importance of eNOS gene polymorphisms in recurrent early pregnancy loss (REPL). We investigated the relationship between idiopathic REPL and polymorphisms in eNOS among South Indian women. Methods: A case-control study comprising 145 females with REPL and 99 control females. The polymorphisms studied include a 27 bp intron 4 repeat, Glu298Asp variation of exon 7 and a novel 140 A→G polymorphism in intron 6. A polymerase chain reaction-based di-deoxy dye terminator sequencing method was used for genotyping. Results: A novel A→G polymorphism was identified in intron 6. The more frequent b allele of intron 4 repeat was present at a frequency of 0.84 in cases as compared to 0.86 in controls (O.R 1.17); the G allele of exon 7 coding for the wild-type glutamate containing isoform was present at a frequency of 0.79 in cases and 0.83 in controls (O.R 1.30, CI 0.6–2.8). The intron 6 variant A allele was present at a frequency of 0.58 in cases and 0.45 in controls (O.R 0.59, CI 0.33–1.08). Overall, the polymorphism in intron 6, in homozygous condition, exhibited a significant association to the risk of REPL (O.R 0.43, CI 0.21–0.89), P: 0.021). Conclusions: The present study identifies and validates a novel polymorphism in the eNOS gene which was found associated with the risk of REPL.

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Acknowledgements

We sincerely acknowledge Dr. Thangaraj for his valuable suggestions during the study. We thank Ms. Jayanthi for her help in patient recruitment and Mr. Arvind for the computational data analysis. We acknowledge Mr. Nagesh, Dr. Manjula and Mr. Anilkumar, Mr. Pavan for their assistance during the DNA sequencing experiments. We are grateful to the Council of Scientific and Industrial Research, New Delhi for the financial assistance supporting the study.

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Authors and Affiliations

  1. Centre for Cellular and Molecular Biology, Uppal Road, 500 007, Hyderabad, Andhra Pradesh, India

    Venkata Suryanarayana, Lakshmi Rao, Murthy Kanakavalli, Venkata Padmalatha & Lalji Singh

  2. Infertility Institute and Research Centre, Secunderabad, Andhra Pradesh, India

    Mamata Deenadayal

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  1. Venkata Suryanarayana
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  2. Lakshmi Rao
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  3. Murthy Kanakavalli
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  4. Venkata Padmalatha
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  5. Mamata Deenadayal
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  6. Lalji Singh
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Correspondence to Lalji Singh.

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Suryanarayana, V., Rao, L., Kanakavalli, M. et al. Recurrent early pregnancy loss and endothelial nitric oxide synthase gene polymorphisms. Arch Gynecol Obstet 274, 119–124 (2006). https://doi.org/10.1007/s00404-005-0107-x

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  • DOI: https://doi.org/10.1007/s00404-005-0107-x

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