Genetic Predisposition Of M2 Annexin A5 Haplotype In Recurrent Pregnancy Loss Among The Malays In Malaysia
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Date
2018-06
Authors
Ang, Kai Cheen
Journal Title
Journal ISSN
Volume Title
Publisher
Universiti Sains Malaysia
Abstract
Repeated Pregnancy Loss (RPL) is a prevalent condition where conventional hereditary thrombophilia factors have been ruled out in Malaysia population. M2/ANXA5 haplotype, a variation at the core promoter region of Annexin A5 (ANXA5) gene, was suggested to be a predisposition factor for RPL. ANXA5 is a placenta anticoagulant protein which binds on the surface of syncitiotrophoblasts to prevent thrombotic events that would lead to RPL. In this study, the prevalence of M2/ANXA5 haplotype was 42.2% in Malay population and 34.9% for parous controls. When compared M2/ANXA5 clinically defined primary and secondary RPL carriers to M2/ANXA5 carriers in random populations, odds ratio of 1.52 (95% CI:1.1 to 2.1) was determined. The highest odds ratio of 1.97 (95% CI: 1.3 to 3.1) was obtained when compared to parous control. Increasing copy numbers of M2/ANXA5 alleles contribute a higher risk in RPL couples, especially when both partners were M2/ANXA5 carriers. This first study confirmed the proposed role of M2/ANXA5 haplotype as a predisposition factor for early primary and secondary RPL among Malay population. Following that, the quantification of the ANXA5 plasma in pregnant and non-pregnant subjects was carried out to seek its potential diagnostic value. However, the results showed no significant differences in ANXA5 plasma levels across non-pregnant, pregnant parous and RPL women, even though there was a trend of significant difference in the ANXA5 plasma levels between M2/ANXA5-carriers and non-carriers (p = 0.02, with post-hoc Bonferoni correction) in the ‘within-group’ analysis. Hence, ANXA5 plasma levels in maternal does not have a diagnostic value for RPL risk estimation as compared to the molecular approach. Next, a RNase H2-dependent PCR
was developed for the screening of M2/ANXA5 haplotype.
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Keywords
Genetic predisposition of m2 annexin a5 haplotype , pregnancy loss among the malays in Malaysia