Kai-Cheen Ang1, Sushilnathan Kathirgamanathan2, Ewe Seng Ch'ng1, Yan-Yeow Lee3, Anna-Liza Roslani4, Bavanandan Naidu5, Krishna Kumar3, Ridzuan Abdullah2, Siti-Nadiah Abdul Kadir6, Narazah Mohd Yusoff1, Wan Zaidah Abdullah7, Nadja Bogdanova8, Peter Wieacker8, Arseni Markoff9, Thean-Hock Tang10,11. 1. Advanced Medical and Dental Institute, University Sains Malaysia, Bertam, Penang, Malaysia. 2. Department of Obstetrics and Gynaecology, Hospital Sultan Abdul Halim, Sungai Petani, Malaysia. 3. Department of Obstetrics and Gynaecology, Hospital Tuanku Jaafar, Seremban, Malaysia. 4. Department of Obstetrics and Gynaecology, Hospital Tengku Ampuan Afzan, Kuantan, Malaysia. 5. Department of Obstetrics and Gynaecology, Hospital Sultanah Bahiyah, Alor Setar, Malaysia. 6. Department of Pathology, Hospital Sultan Abdul Halim, Sungai Petani, Malaysia. 7. Department of Haematology, School of Medical Sciences, Universiti Sains Malaysia, Kubang Kerian, Malaysia. 8. Institute of Human Genetics, University of Muenster, Muenster, Germany. 9. Institute of Human Genetics, University of Muenster, Muenster, Germany. markoff@uni-muenster.de. 10. Advanced Medical and Dental Institute, University Sains Malaysia, Bertam, Penang, Malaysia. tangth@usm.my. 11. Advanced Medical and Dental Institute (AMDI), Universiti Sains Malaysia, 13200 Bertam, Kepala Batas, Penang, Malaysia. tangth@usm.my.
Abstract
PURPOSE: The aim of this study was to evaluate a new predisposition factor, M2/ANXA5 (RPRGL3), in recurrent pregnancy loss (RPL) patients of Malay origin, since it was previously known that the prevalence of this condition is relatively high among the Malay population of Malaysia, where conventional hereditary thrombophilia factors have been generally ruled out. METHODS: A total of 232 women who had experienced ≥2 unexplained RPL and 141 available male partners were recruited, with 360 healthy Malay and 166 parous female controls. Prevalence of M2 carriage and RPL odds ratios were calculated in (a) control and patient groups; (b) clinically defined subgroups in categories of pregnancy loss, primary, secondary, and tertiary; and (c) timing of pregnancy loss in early, ≤15th gestation week and "late" fetal losses, and >15th gestation week subgroups. RESULTS: Both male and female subjects had similar M2/ANXA5 allele frequencies. The carrier rate of M2/ANXA5 for the general Malay population was 42.2 and 34.9% for parous controls. These carrier rates compared to Malay RPL subjects (52% M2 carriers) resulted in elevated odds ratios (95% confidence interval) of 1.53 (1.1 to 2.1) and 1.97 (1.3 to 3.1) accordingly for early fetal losses. Moreover, exceeding copy numbers of M2/ANXA5 alleles seemed to afflict a greater chance of RPL in couples, especially when both partners were M2 carriers. CONCLUSION: This study confirmed the proposed role of M2/ANXA5 as embryonic, genetically associated thrombophilia predisposition factor for early RPL among ethnic Malay of Malaysia.
PURPOSE: The aim of this study was to evaluate a new predisposition factor, M2/ANXA5 (RPRGL3), in recurrent pregnancy loss (RPL) patients of Malay origin, since it was previously known that the prevalence of this condition is relatively high among the Malay population of Malaysia, where conventional hereditary thrombophilia factors have been generally ruled out. METHODS: A total of 232 women who had experienced ≥2 unexplained RPL and 141 available male partners were recruited, with 360 healthy Malay and 166 parous female controls. Prevalence of M2 carriage and RPL odds ratios were calculated in (a) control and patient groups; (b) clinically defined subgroups in categories of pregnancy loss, primary, secondary, and tertiary; and (c) timing of pregnancy loss in early, ≤15th gestation week and "late" fetal losses, and >15th gestation week subgroups. RESULTS: Both male and female subjects had similar M2/ANXA5 allele frequencies. The carrier rate of M2/ANXA5 for the general Malay population was 42.2 and 34.9% for parous controls. These carrier rates compared to Malay RPL subjects (52% M2 carriers) resulted in elevated odds ratios (95% confidence interval) of 1.53 (1.1 to 2.1) and 1.97 (1.3 to 3.1) accordingly for early fetal losses. Moreover, exceeding copy numbers of M2/ANXA5 alleles seemed to afflict a greater chance of RPL in couples, especially when both partners were M2 carriers. CONCLUSION: This study confirmed the proposed role of M2/ANXA5 as embryonic, genetically associated thrombophilia predisposition factor for early RPL among ethnic Malay of Malaysia.
Entities:
Keywords:
Annexin A5; M2/ANXA5; Miscarriage; Recurrent pregnancy loss (RPL)
Authors: K O Kagan; J Sonek; X Berg; C Berg; M Mallmann; H Abele; M Hoopmann; A Geipel Journal: Ultrasound Obstet Gynecol Date: 2015-06-01 Impact factor: 7.299
Authors: Narazah Mohd Yusoff; Wan Zaidah Abdullah; Selamah Ghazali; Mohd Shukri Othman; Abdul Aziz Baba; Norazmi Abdullah; Mohd Nizam Isa; Chan Li Chong Journal: Aust N Z J Obstet Gynaecol Date: 2002-05 Impact factor: 2.100
Authors: Pedro A Soares; Jean A Trejaut; Teresa Rito; Bruno Cavadas; Catherine Hill; Ken Khong Eng; Maru Mormina; Andreia Brandão; Ross M Fraser; Tse-Yi Wang; Jun-Hun Loo; Christopher Snell; Tsang-Ming Ko; António Amorim; Maria Pala; Vincent Macaulay; David Bulbeck; James F Wilson; Leonor Gusmão; Luísa Pereira; Stephen Oppenheimer; Marie Lin; Martin B Richards Journal: Hum Genet Date: 2016-01-18 Impact factor: 4.132