Annexin A5 Promoter Haplotype M2 Is Not a Risk Factor for Recurrent Pregnancy Loss in Northern Europe
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Annexin A5 Promoter Haplotype M2 Is Not a Risk Factor for Recurrent Pregnancy Loss in Northern Europe. / Nagirnaja, Liina; Nõmmemees, Diana; Rull, Kristiina; Christiansen, Ole B; Nielsen, Henriette Svarre; Laan, Maris.
In: P L o S One, Vol. 10, No. 7, e0131606, 2015, p. 1-15.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Annexin A5 Promoter Haplotype M2 Is Not a Risk Factor for Recurrent Pregnancy Loss in Northern Europe
AU - Nagirnaja, Liina
AU - Nõmmemees, Diana
AU - Rull, Kristiina
AU - Christiansen, Ole B
AU - Nielsen, Henriette Svarre
AU - Laan, Maris
PY - 2015
Y1 - 2015
N2 - INTRODUCTION: Annexin A5 is an essential component of placental integrity that may potentially mediate susceptibility to phenotypes of compromised pregnancy. A promoter haplotype termed M2 of the coding gene ANXA5 has been implicated in various pregnancy complications such as preeclampsia and recurrent pregnancy loss (RPL), however with inconclusive results.STUDY SUBJECTS AND METHODS: A retrospective case-control study combining resequencing and restriction fragment length polymorphism (RFLP) analysis was undertaken in 313 women with unexplained RPL and 214 fertile women from Estonia and Denmark to estimate the RPL disease risk of the M2 haplotype in Northern Europe. Comparative prevalence of the studied ANXA5 genetic variants in human populations was estimated based on the 1000 Genomes Project (n = 675, whole-genome sequencing data) and the KORA S3 500K dataset of South German samples (n = 1644, genome-wide genotyping data).RESULTS: Minor allele frequency of common polymorphisms in ANXA5 promoter was up to two-fold lower among Estonian RPL subjects than fertile controls. The M2 haplotype was not associated with RPL and a trend for decreased prevalence was observed among RPL patients compared to controls both in Estonia (8.1% vs 15.2%, respectively) and Denmark (9.7% vs 12.6%). The high M2 prevalence in fertile controls was consistent with estimations for European and East Asian populations (9.6%-16.0%).CONCLUSIONS: This study cautions to consider the M2 haplotype as a deterministic factor in early pregnancy success because: i) no RPL disease risk was associated with the haplotype in two clinically well-characterized RPL case-control study samples, ii) high prevalence of the haplotype among fertile controls and world-wide populations is inconsistent with the previously proposed severe impact on early pregnancy success, iii) weak impact of M2 haplotype on the production of ANXA5 protein has been established by others.
AB - INTRODUCTION: Annexin A5 is an essential component of placental integrity that may potentially mediate susceptibility to phenotypes of compromised pregnancy. A promoter haplotype termed M2 of the coding gene ANXA5 has been implicated in various pregnancy complications such as preeclampsia and recurrent pregnancy loss (RPL), however with inconclusive results.STUDY SUBJECTS AND METHODS: A retrospective case-control study combining resequencing and restriction fragment length polymorphism (RFLP) analysis was undertaken in 313 women with unexplained RPL and 214 fertile women from Estonia and Denmark to estimate the RPL disease risk of the M2 haplotype in Northern Europe. Comparative prevalence of the studied ANXA5 genetic variants in human populations was estimated based on the 1000 Genomes Project (n = 675, whole-genome sequencing data) and the KORA S3 500K dataset of South German samples (n = 1644, genome-wide genotyping data).RESULTS: Minor allele frequency of common polymorphisms in ANXA5 promoter was up to two-fold lower among Estonian RPL subjects than fertile controls. The M2 haplotype was not associated with RPL and a trend for decreased prevalence was observed among RPL patients compared to controls both in Estonia (8.1% vs 15.2%, respectively) and Denmark (9.7% vs 12.6%). The high M2 prevalence in fertile controls was consistent with estimations for European and East Asian populations (9.6%-16.0%).CONCLUSIONS: This study cautions to consider the M2 haplotype as a deterministic factor in early pregnancy success because: i) no RPL disease risk was associated with the haplotype in two clinically well-characterized RPL case-control study samples, ii) high prevalence of the haplotype among fertile controls and world-wide populations is inconsistent with the previously proposed severe impact on early pregnancy success, iii) weak impact of M2 haplotype on the production of ANXA5 protein has been established by others.
KW - Abortion, Habitual
KW - Adult
KW - Alleles
KW - Annexin A5
KW - Case-Control Studies
KW - Denmark
KW - Estonia
KW - Female
KW - Genetic Predisposition to Disease
KW - Genome-Wide Association Study
KW - Genotype
KW - Haplotypes
KW - Humans
KW - Middle Aged
KW - Phenotype
KW - Placenta
KW - Polymorphism, Genetic
KW - Polymorphism, Restriction Fragment Length
KW - Pre-Eclampsia
KW - Pregnancy
KW - Prevalence
KW - Promoter Regions, Genetic
KW - Retrospective Studies
KW - Risk Factors
KW - Young Adult
U2 - 10.1371/journal.pone.0131606
DO - 10.1371/journal.pone.0131606
M3 - Journal article
C2 - 26135579
VL - 10
SP - 1
EP - 15
JO - PLoS ONE
JF - PLoS ONE
SN - 1932-6203
IS - 7
M1 - e0131606
ER -
ID: 161848505