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Molecular associations of recurrent spontaneous abortion

Berger, Dara Suzanne (2007) Molecular associations of recurrent spontaneous abortion. Doctoral Dissertation, University of Pittsburgh. (Unpublished)

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Approximately one in four pregnant women experience one or more miscarriages, making spontaneous abortion the most common pregnancy complication, and of public health importance. Recurrent spontaneous abortion (RSA) can be defined as the loss of two or more pregnancies and affects 1% of couples. This prevalence is higher than expected by chance, suggesting some couples have an underlying systemic cause for RSA. We have chosen to study two immunological aspects of pregnancy loss. The first involves maternal defense against infection in terms of predicted mannose binding lectin (MBL) plasma levels. The second approach is to analyze the human leukocyte antigen-G (HLA-G) gene, which is believed to play a role in maternal recognition of paternal antigens at the maternal-fetal interface. The case population included women having two or more clinically recognized spontaneous abortions as well as having unknown etiology for RSA. Controls subjects were selected from healthy primiparous women with no history of miscarriage. Cases and controls were genotyped for five MBL single nucleotide polymorphisms (SNPs). Both populations genotyped were in Hardy-Weinberg equilibrium, at all five sites. Fisher's exact test of cases and controls was not significant at each of the five sites, p-values > 0.05. No association was observed between MBL genotypes or predicted MBL plasma levels and risk of RSA, or presence of live birth and recurrent pregnancy loss, among women with unexplained RSA. Using the same population, the HLA-G promoter region and 3' untranslated region (UTR) was sequenced in cases and controls. Twenty-three SNPs were observed with a minor allele frequency >0.02 in the promoter region. Linkage disequilibrium was detected throughout 1400 base pairs of the promoter region that were sequenced. While SNP data revealed allele frequency differences between cases and controls, haplotype data proved even more beneficial; one haplotype potentially predicting increased risk of RSA, while the other potentially protecting against risk of RSA. Finally, cases had a higher frequency of individuals homozygous for the 14 base pair insertion in the 3' UTR.


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Item Type: University of Pittsburgh ETD
Status: Unpublished
CreatorsEmailPitt UsernameORCID
Berger, Dara
ETD Committee:
TitleMemberEmail AddressPitt UsernameORCID
Committee ChairFerrell, Robertrferrell@hgen.pitt.eduRFERRELL
Committee MemberKammerer, Candaceckammerer@hgen.pitt.eduCMK3
Committee MemberBarmada, Michaelmbarmada@hgen.pitt.eduBARMADA
Committee MemberHogge, W.
Date: 20 February 2007
Date Type: Completion
Defense Date: 13 July 2006
Approval Date: 20 February 2007
Submission Date: 4 December 2006
Access Restriction: No restriction; Release the ETD for access worldwide immediately.
Institution: University of Pittsburgh
Schools and Programs: Graduate School of Public Health > Human Genetics
Degree: PhD - Doctor of Philosophy
Thesis Type: Doctoral Dissertation
Refereed: Yes
Uncontrolled Keywords: haplotype; MBL; genotype; HLA-G
Other ID:, etd-12042006-193014
Date Deposited: 10 Nov 2011 20:07
Last Modified: 15 Nov 2016 13:53


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