Women with a history of recurrent miscarriage have a genetic predisposition to the HLA-G 3′UTR 14-bp insertion allele but increased HLA-G expression in their term placenta

Human leukocyte antigen (HLA)-G is an immune modulating molecule that is present on fetal extravillous trophoblasts at the fetal-maternal interface. Single nucleotide polymorphisms (SNPs) in the 3 prime untranslated region (3′UTR) of the HLA-G gene can affect the level of HLA-G expression, which may be altered in women with recurrent miscarriages (RM). This case-control study included 23 women with a medical history of three or more consecutive miscarriages who delivered a child after uncomplicated pregnancy, and 46 controls with uncomplicated pregnancy. Genomic DNA was isolated to sequence the 3′UTR of HLA-G. Tissue from term placentas was processed to quantify the HLA-G protein and mRNA levels. The women with a history of RM had a lower frequency of the HLA-G 3′UTR 14-bp del/del genotype as compared to controls (Odds ratio (OR) 0.28; p = 0.039), which has previously been related to higher soluble HLA-G levels. Yet, HLA-G protein (OR 6.67; p = 0.006) and mRNA (OR 6.33; p = 0.010) expression was increased in term placentas of women with a history of RM as compared to controls. In conclusion, during a successful pregnancy, HLA-G expression is elevated in term placentas from women with a history of RM as compared to controls, despite a genetic predisposition that is associated with decreased HLA-G levels. These findings suggest that HLA-G upregulation could be a compensatory mechanism in the occurrence of RM to achieve an ongoing pregnancy.

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Review for "Uterine CD56 + cell density and euploid miscarriage in women with a history of recurrent miscarriage: a clinical descriptive study"

10.1002/eji.202048868/v2/review1 ◽

2020 ◽

Author(s):

Felix Martinus Wensveen

Keyword(s):

Cell Density ◽

Recurrent Miscarriage ◽

Descriptive Study ◽

History Of

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Vitamin D status and risk of type 2 diabetes in the Norwegian HUNT cohort study: does family history or genetic predisposition modify the association?

BMJ Open Diabetes Research & Care ◽

10.1136/bmjdrc-2020-001948 ◽

2021 ◽

Vol 9 (1) ◽

pp. e001948

Author(s):

Marion Denos ◽

Xiao-Mei Mai ◽

Bjørn Olav Åsvold ◽

Elin Pettersen Sørgjerd ◽

Yue Chen ◽

...

Keyword(s):

Type 2 Diabetes ◽

Family History ◽

Genetic Predisposition ◽

Effect Modification ◽

P Value ◽

Family History Of Diabetes ◽

Increased Risk ◽

History Of

IntroductionWe sought to investigate the relationship between serum 25-hydroxyvitamin D (25(OH)D) level and the risk of type 2 diabetes mellitus (T2DM) in adults who participated in the Trøndelag Health Study (HUNT), and the possible effect modification by family history and genetic predisposition.Research design and methodsThis prospective study included 3574 diabetes-free adults at baseline who participated in the HUNT2 (1995–1997) and HUNT3 (2006–2008) surveys. Serum 25(OH)D levels were determined at baseline and classified as <50 and ≥50 nmol/L. Family history of diabetes was defined as self-reported diabetes among parents and siblings. A Polygenic Risk Score (PRS) for T2DM based on 166 single-nucleotide polymorphisms was generated. Incident T2DM was defined by self-report and/or non-fasting glucose levels greater than 11 mmol/L and serum glutamic acid decarboxylase antibody level of <0.08 antibody index at the follow-up. Multivariable logistic regression models were applied to calculate adjusted ORs with 95% CIs. Effect modification by family history or PRS was assessed by likelihood ratio test (LRT).ResultsOver 11 years of follow-up, 92 (2.6%) participants developed T2DM. A higher risk of incident T2DM was observed in participants with serum 25(OH)D level of<50 nmol/L compared with those of ≥50 nmol/L (OR 1.72, 95% CI 1.03 to 2.86). Level of 25(OH)D<50 nmol/L was associated with an increased risk of T2DM in adults without family history of diabetes (OR 3.87, 95% CI 1.62 to 9.24) but not in those with a family history (OR 0.72, 95% CI 0.32 to 1.62, p value for LRT=0.003). There was no effect modification by PRS (p value for LRT>0.23).ConclusionSerum 25(OH)D<50 nmol/L was associated with an increased risk of T2DM in Norwegian adults. The inverse association was modified by family history of diabetes but not by genetic predisposition to T2DM.

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Association of +505A>G Polymorphism at TAFI Gene with Recurrent Miscarriage in Iranian Women

World Journal of Peri & Neonatology ◽

10.18502/wjpn.v3i2.6156 ◽

2021 ◽

Author(s):

Razieh Alivand ◽

Fatemeh Abdi ◽

Mahmood Dehghani-Ashkezari ◽

Hossein Neamatzadeh ◽

Sedigheh Ekraminasab

Keyword(s):

Recurrent Miscarriage ◽

Iranian Women ◽

Specific Pcr ◽

Study Results ◽

Significant Difference ◽

Fibrinolysis Inhibitor ◽

History Of ◽

Allele Specific ◽

Allele Specific Pcr ◽

Control Study

Background: Recurrent miscarriage (RM) is one of the major problems of public health globally. The thrombin-activatable fibrinolysis inhibitor (TAFI) gene is a plasma zymogen that regulates both fibrinolysis and inflammation. Genetic variants within TAFI gene are presumed to be associated with development of RM. This case-control study aimed to investigate the association of TAFI +505A>G polymorphism with RM in Iranian women referred to Meybod Genetic Center. Methods: Fifty women with RM (at least 2 miscarriages) and 50 healthy women with no history of miscarriage or other fertility complications were participated in this study. The TAFI +505A>G polymorphism was genotyped by allele specific PCR (AS-PCR) assay. Results: The mean age of cases with RM and controls was 27.25 ± 4.31 and 28.42 ± 3.22 years, respectively. The frequency of GG genotype and G allele was 0.00% in patients and controls. There was no significant difference between RM cases and controls in terms of +505A>G genotypes and alleles. Conclusion: This study results indicated that there was no significant relationship between the TAFI +505A>G polymorphism and RM risk in Iranian women. However, further rigorous, studies with a larger sample size and different ethnicity are necessary to confirm our findings.

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Association of serum progesterone level and endometrial estradiol & progesterone receptors in women with unexplained recurrent miscarriage

QJM ◽

10.1093/qjmed/hcab115.004 ◽

2021 ◽

Vol 114 (Supplement_1) ◽

Author(s):

Ihab Found Alam ◽

Sherif Ahmed Ashoush ◽

Ihab Adel Gomaa ◽

Ahmed Sabry AbdEl-Hafeez

Keyword(s):

Menstrual Cycle ◽

Recurrent Miscarriage ◽

Progesterone Receptors ◽

First Trimester ◽

Endometrial Biopsy ◽

Serum Progesterone ◽

Normal Endometrium ◽

History Of ◽

Unexplained Recurrent Miscarriage

Abstract This study investigated the endometrial tissue to study the fluctuation of estrogen receptors (ERs) and progesterone receptors (PRs) in women with recurrent miscarriage compared with normal endometrium of fertile women. Forty women were divided into two groups: 20 non-pregnant women with history of recurrent miscarriage (who had three or more first- trimester miscarriages) and 20 controls. Both groups had regular ovulatory menses and proven fertility. Endometrial biopsy was taken in the two groups during the luteal phase of the menstrual cycle, between the 8th and the 10th postovulatory days using an endometrial biopsy curette for determination of estrogen (E2) and progesterone (P4) hormones levels and their receptors. On the same day as the biopsy, a blood sample was taken for determination of estradiol (E2) and progesterone (P4) levels. The obtained results showed no significant differences between both groups regarding age, BMI, menarche, menstrual cycle & menstruation, significant decrease in E2 and P4 levels in the serum and endometrial biopsy of recurrent miscarriage women versus control. In control and recurrent miscarriage; ER levels in cytoplasm and salt extracted nucleus were higher than PR levels. ER and PR values were higher in the nuclear compartment than in the cytoplasmic compartment. The women with early recurrent miscarriage showed lower levels of both ER and PR significantly. All types of endometrial receptors (ER &PR) and hormones (E2 &P4) in serum and endometrium showed correlation relating to number of previous miscarriages.

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A different point of view regarding cardiovascular risk in women with a history of recurrent miscarriage

Acta Obstetricia Et Gynecologica Scandinavica ◽

10.1111/aogs.13494 ◽

2018 ◽

Vol 98 (3) ◽

pp. 402-402

Author(s):

Kazim Emre Karaşahin

Keyword(s):

Cardiovascular Risk ◽

Recurrent Miscarriage ◽

Point Of View ◽

History Of

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Serum TNF-α, IL-6, lupus anticoagulant and anticardiolipin antibody in women with and without a past history of recurrent miscarriage

Archives of Gynecology and Obstetrics ◽

10.1007/s00404-003-0547-0 ◽

2004 ◽

Vol 270 (4) ◽

pp. 227-229 ◽

Cited By ~ 25

Author(s):

Emine Arslan ◽

Mehmet Çolakoğlu ◽

Çetin Çelik ◽

Kazim Gezginç ◽

Ali Acar ◽

...

Keyword(s):

Lupus Anticoagulant ◽

Recurrent Miscarriage ◽

Past History ◽

Anticardiolipin Antibody ◽

Tnf Α ◽

History Of

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Recurrent Miscarriage and Consanguinity among Omani Women– A Cross Sectional Study

Gynecology & Reproductive Health ◽

10.33425/2639-9342.1141 ◽

2021 ◽

Vol 5 (1) ◽

Author(s):

Fatma Al Hoqani ◽

Wadha Al Ghafri ◽

Saneya El tayeb ◽

Yahya Al Farsi ◽

Vaidyanathan Gowri

Keyword(s):

Recurrent Miscarriage ◽

Cross Sectional Study ◽

University Hospital ◽

Control Group ◽

P Value ◽

Cross Sectional ◽

Recurrent Miscarriages ◽

Sultan Qaboos University ◽

Chi Squared ◽

History Of

Objective: to determine the prevalence of explained and unexplained recurrent miscarriages (RM) and to find out if there is a significant relationship between recurrent miscarriages and consanguinity. Methods: A cross sectional in which the cases group included all women with RM attending the outpatient clinic at Sultan Qaboos University Hospital from July 2006 to April 2012 and the controls group included women with no history of RM after matching them with cases for age (case to control ratio was 1:1). The main outcome measures were the prevalence of consanguinity in women with or without recurrent miscarriages. Results: During study period a total of 290 women with RM were seen. Of which, 150 (51.7%) women had unexplained RM. Control group with no history of RM were 300 women. Consanguinity rate among cases (49.5%) %) was less than the controls (52.7 %%). Both first cousin and second cousin marriages were more common in the controls than the cases and it was not statistically significant (p value 0.476, chi squared test). Conclusion: In this study we found that more than half of RM cases were unexplained and there was no significant association between RM and consanguinity.

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