Association of functional genetic variants of CTLA4 with reduced serum CTLA4 protein levels and increased risk of idiopathic recurrent miscarriages Maneesh.

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Association of functional genetic variants of CTLA4 with reduced serum CTLA4 protein levels and increased risk of idiopathic recurrent miscarriages Maneesh Kumar Misra, Ph.D., Aditi Mishra, M.Tech., Shubha R. Phadke, D.M., Suraksha Agrawal, Ph.D. Fertility and Sterility Volume 106, Issue 5, Pages 1115-1123.e6 (October 2016) DOI: 10.1016/j.fertnstert.2016.06.011 Copyright © 2016 American Society for Reproductive Medicine Terms and Conditions

Figure 1 Normalized soluble CTLA4 serum concentrations in women with idiopathic recurrent miscarriage (IRM) for the CTLA4 tag-single-nucleotide polymorphisms (SNPs): (A) rs231775 and (B) rs3087243. Grey boxes represent the interquartile range, encompassing the first through third quartile; the horizontal bar shows the median value. Values greater than 1.5 times the interquartile range are plotted outside of the whiskers. The Kruskal-Wallis test was performed to obtain the P value. *Statistically significant risk for IRM. Fertility and Sterility 2016 106, 1115-1123.e6DOI: (10.1016/j.fertnstert.2016.06.011) Copyright © 2016 American Society for Reproductive Medicine Terms and Conditions

Supplemental Figure 1 Overview of haplotype tag single-nucleotide polymorphisms (htSNPs) within the CTLA4 gene in Hapmap-GIH population. The image was generated using HAPLOVIEW (version 4.2) program using CTLA4 tag-SNPs with minor-allele frequencies >1%. Each box provides an estimated value of the pairwise correlation coefficient r2 between tag-SNPs, with darker shades representing stronger linkage disequilibrium and white shades suggesting no linkage disequilibrium. Fertility and Sterility 2016 106, 1115-1123.e6DOI: (10.1016/j.fertnstert.2016.06.011) Copyright © 2016 American Society for Reproductive Medicine Terms and Conditions

Supplemental Figure 2 Distribution of genotype and allele frequencies of CTLA4 rs231775 and rs3087243 tag-SNPs in women with idiopathic recurrent miscarriage (IRM) and control women. *Statistically significant; ns = not statistically significant. Fertility and Sterility 2016 106, 1115-1123.e6DOI: (10.1016/j.fertnstert.2016.06.011) Copyright © 2016 American Society for Reproductive Medicine Terms and Conditions

Supplemental Figure 3 Protein–protein interaction network of CTLA4. Each node represents a protein and edges, that is, the predicted functional links between proteins. Stronger associations are represented by thicker lines. Fertility and Sterility 2016 106, 1115-1123.e6DOI: (10.1016/j.fertnstert.2016.06.011) Copyright © 2016 American Society for Reproductive Medicine Terms and Conditions