Associations between cytokine gene polymorphisms and recurrent pregnancy loss

Daher, Sílvia; Shulzhenko, Natalia; Morgun, Andrey; Mattar, Rosiane; Rampim, Gisele F; Camano, Luiz; DeLima, Maria Gerbase

doi:10.1016/s0165-0378(02)00059-1

Cited by 135 publications

(109 citation statements)

References 24 publications

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“…6 Cytokine gene polymorphisms have been associated with certain inflammatory and infectious diseases, including some obstetric disorders. [7][8][9][10] The relationship between PE and single-nucleotide polymorphisms (SNPs) in cytokine genes has been investigated, but is still unclear. [11][12][13][14][15] The controversial results reported by different investigators may in part be because of selection criteria.…”

Section: Introductionmentioning

confidence: 99%

Cytokine gene polymorphisms in preeclampsia and eclampsia

Lima¹,

Sass

Mattar

et al. 2009

Hypertens Res

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The clinical spectrum of preeclampsia (PE) ranges from mild hypertension to severe vasospasm associated with convulsions and multiple organ damage. The biological factors that determine the progression of PE to eclampsia (E) are unknown. Endothelial cell activation seems related to an impaired maternal immune response. The production of cytokines, IL-10 and TGF-b1, is apparently suppressed, and altered IL-2/IL-10 and TNF-a/IL-10 ratios have been reported in preeclamptic cases. The relationship between PE and cytokine gene polymorphism has been studied, but there are few studies that include eclamptic patients. This study aimed at investigating whether polymorphisms in genes, TNF-a promoter (À308 G4A), IL6 promoter (À174 G4C), IFN-c intron 1 (+874 A4T), IL10 promoters (À1082 A4G), (À819 C4T) and (À592 C4A) and TGF-b1 codon 10 (+869 T4C) and codon 25 (+915 G4C) are associated with E and/or PE. Genotyping was carried out in 266 Mulatto women from the northeastern region of Brazil who were referred to a single maternity hospital: 92 with PE, 73 with E and 101 normotensive controls. The v 2 or Fisher's exact tests were used to compare genotype frequencies. Among the six singlenucleotide polymorphisms (SNPs) studied, we found no difference in genotype frequencies between the groups. There was a higher frequency of IFN-c (+874 A) in eclamptic patients in comparison with that in controls. (70.3 vs. 57.8%, respectively; P¼0.02). There were no other significant differences in allelic frequencies between eclamptic, preeclamptic and control groups We found no independent association between any single SNP and PE or E risk in this population of Mulatto women from the northeastern region of Brazil.

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Section: Introductionmentioning

confidence: 99%

Cytokine gene polymorphisms in preeclampsia and eclampsia

Lima¹,

Sass

Mattar

et al. 2009

Hypertens Res

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“…The main objective of the present study was to determine the effect of IL-10 -1082G/A gene promoter polymorphism in spontaneously aborted foetuses in addition to their parental groups. IL-10 serves a dual role in the production of pro-inflammatory cytokines and acts as an important anti-inflammatory cytokine at foeto-placental interface [21][22][23]. Pro-inflammatory cytokines (IL-1, IL-2, IL-12, IFN-γ, TNF-∝, IF-3) and anti-inflammatory cytokines (IL-4, IL-13, TGF-β) counter regulate each other such that they maintain a balance in their production resulting in normal pregnancy.…”

Section: Discussionmentioning

confidence: 99%

A functional polymorphism in the promoter region of interleukin-10 gene increases the risk for spontaneous abortions—a triad study

Vidyadhari

Sujatha

Krupa³

et al. 2015

J Assist Reprod Genet

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Purpose Spontaneous abortion or miscarriage is the natural death of an embryo or foetus in the early stages of prenatal development. Interleukin-10 is an anti-inflammatory cytokine, produced by human cytotrophoblasts, and defects in its production result in specific pathological conditions during pregnancy. The present study is aimed to evaluate the association of IL-10 -1082G/A polymorphism in spontaneous abortions by comparing foetal, maternal and paternal groups-a triad study. Methods A total of 50 families with spontaneous abortions and 60 families with medically terminated pregnancies were considered for the present study. DNA from foetal tissue and parental blood samples were extracted, and the genotype analysis of IL-10 -1082G/A promoter polymorphism was carried out by amplification refractory mutation system-polymerase chain reaction followed by agarose gel electrophoresis. A statistical analysis was applied to test for the significance of the results. Results There was a statistically significant difference in the distribution of AA genotypes and A allele of IL-10 -1082G/A between the two family groups among foetuses (P=0.0002) and mothers (P=0.00005).

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“…One meta-analysis performed did not show any significant association between RPL and genetic polymorphisms of IL-10, however other individual studies have noted a statistically significant associations (especially with IL-10 alleles -1082 and -592) [77,115,117,119,120]. Overall, the role of IL-10 in RPL still needs further exploration.…”

Section: Il-10mentioning

confidence: 93%

Immunogenetic contributions to recurrent pregnancy loss

Grimstad

Krieg

2016

J Assist Reprod Genet

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While sporadic pregnancy loss is common, occurring in 15 % of pregnancies, recurrent pregnancy loss (RPL) impacts approximately 5 % of couples. Though multiple causes are known (including structural, hormonal, infectious, autoimmune, and thrombophilic causes), after evaluation, roughly half of all cases remain unexplained. The idiopathic RPL cases pose a challenging therapeutic dilemma in addition to incurring much physical and emotional morbidity. Immunogenetic causes have been postulated to contribute to these cases of RPL. Natural Killer cell, T cell expression pattern changes in the endometrium have both been shown in patients with RPL. Human leukocyte antigen (HLA) and cytokine allelic variations have also been studied as etiologies for RPL. Some of the results have been promising, however the studies are small and have not yet put forth outcomes that would change our current diagnosis and management of RPL. Larger database studies are needed with stricter control criteria before reasonable conclusions can be drawn.

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Associations between cytokine gene polymorphisms and recurrent pregnancy loss

Cited by 135 publications

References 24 publications

Cytokine gene polymorphisms in preeclampsia and eclampsia

Cytokine gene polymorphisms in preeclampsia and eclampsia

A functional polymorphism in the promoter region of interleukin-10 gene increases the risk for spontaneous abortions—a triad study

Immunogenetic contributions to recurrent pregnancy loss

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