title: Genetic analysis of the M2/ANXA5 haplotype as recurrent pregnancy loss predisposition in the Malay population.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  This study confirmed the proposed role of M2/ANXA5 as embryonic, genetically associated thrombophilia predisposition factor for early RPL among ethnic Malay of Malaysia.
authors.affiliation: Advanced Medical and Dental Institute, University Sains Malaysia, Bertam, Penang, Malaysia.
authors.forename: Kai-Cheen
authors.initials: KC
authors.lastname: Ang
authors.affiliation: Department of Obstetrics and Gynaecology, Hospital Sultan Abdul Halim, Sungai Petani, Malaysia.
authors.forename: Sushilnathan
authors.initials: S
authors.lastname: Kathirgamanathan
authors.affiliation: Advanced Medical and Dental Institute, University Sains Malaysia, Bertam, Penang, Malaysia.
authors.forename: Ewe Seng
authors.initials: ES
authors.lastname: Ch'ng
authors.affiliation: Department of Obstetrics and Gynaecology, Hospital Tuanku Jaafar, Seremban, Malaysia.
authors.forename: Yan-Yeow
authors.initials: YY
authors.lastname: Lee
authors.affiliation: Department of Obstetrics and Gynaecology, Hospital Tengku Ampuan Afzan, Kuantan, Malaysia.
authors.forename: Anna-Liza
authors.initials: AL
authors.lastname: Roslani
authors.affiliation: Department of Obstetrics and Gynaecology, Hospital Sultanah Bahiyah, Alor Setar, Malaysia.
authors.forename: Bavanandan
authors.initials: B
authors.lastname: Naidu
authors.affiliation: Department of Obstetrics and Gynaecology, Hospital Tuanku Jaafar, Seremban, Malaysia.
authors.forename: Krishna
authors.initials: K
authors.lastname: Kumar
authors.affiliation: Department of Obstetrics and Gynaecology, Hospital Sultan Abdul Halim, Sungai Petani, Malaysia.
authors.forename: Ridzuan
authors.initials: R
authors.lastname: Abdullah
authors.affiliation: Department of Pathology, Hospital Sultan Abdul Halim, Sungai Petani, Malaysia.
authors.forename: Siti-Nadiah Abdul
authors.initials: SA
authors.lastname: Kadir
authors.affiliation: Advanced Medical and Dental Institute, University Sains Malaysia, Bertam, Penang, Malaysia.
authors.forename: Narazah Mohd
authors.initials: NM
authors.lastname: Yusoff
authors.affiliation: Department of Haematology, School of Medical Sciences, Universiti Sains Malaysia, Kubang Kerian, Malaysia.
authors.forename: Wan Zaidah
authors.initials: WZ
authors.lastname: Abdullah
authors.affiliation: Institute of Human Genetics, University of Muenster, Muenster, Germany.
authors.forename: Nadja
authors.initials: N
authors.lastname: Bogdanova
authors.affiliation: Institute of Human Genetics, University of Muenster, Muenster, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Wieacker
authors.affiliation: Institute of Human Genetics, University of Muenster, Muenster, Germany. markoff@uni-muenster.de.
authors.forename: Arseni
authors.identifier: http://orcid.org/0000-0002-7134-3452
authors.initials: A
authors.lastname: Markoff
authors.affiliation: Advanced Medical and Dental Institute, University Sains Malaysia, Bertam, Penang, Malaysia. tangth@usm.my.|Advanced Medical and Dental Institute (AMDI), Universiti Sains Malaysia, 13200 Bertam, Kepala Batas, Penang, Malaysia. tangth@usm.my.
authors.forename: Thean-Hock
authors.initials: TH
authors.lastname: Tang
mesh_terms: D000026:Abortion, Habitual / Q000235:genetics* / Q000503:physiopathology; D000328:Adult; D017304:Annexin A5 / Q000235:genetics*; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing; D005838:Genotype; D006239:Haplotypes; D006579:Heterozygote; D006801:Humans; D008297:Male; D011247:Pregnancy; D012307:Risk Factors; D055815:Young Adult
chemical_list: D017304:Annexin A5
keywords: Annexin A5; M2/ANXA5; Miscarriage; Recurrent pregnancy loss (RPL)