Cytokine Gene Polymorphisms in Recurrent Pregnancy Loss of Unknown Cause

Prigoshin, Norma; Tambutti, Mónica L.; Larriba, J.; Gogorza, S.; Testa, Roberto

doi:10.1111/j.1600-0897.2004.00179.x

Cited by 80 publications

(77 citation statements)

References 27 publications

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“…It has been shown to be elevated in RPL patients [13,72,78,79,124]. Significant associations between RPL and the IFN-γ(+874) polymorphisms have been found [115,119,120]. However, a metaanalysis performed did not show any significant association between RPL and any genetic polymorphisms of IFN-γ [77].…”

Section: Ifn-γmentioning

confidence: 73%

“…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: 96%

“…However, two studies performed did not show any significant association between RPL and genetic polymorphisms of TNF-α [77,120]. If there is a relationship it is possibly a weak one.…”

Section: Tnf-αmentioning

confidence: 99%

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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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Section: Ifn-γmentioning

confidence: 73%

Section: Il-10mentioning

confidence: 96%

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Immunogenetic contributions to recurrent pregnancy loss

Grimstad

Krieg

2016

J Assist Reprod Genet

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“…Subsequently, three documents were excluded for being review articles [37][38][39]. Thus, 15 relevant studies met the inclusion criteria [14][15][16][17][18][19][20][21][22][23][24][25][26][27][28]), of which, eight were related to the IL-6 −174 G/C polymorphism and involved 859 patients and 1018 controls, four concerned the IL-6 −634 G/C polymorphism and included 343 patients and 340 controls, while six referred to the IFN-γ +874 A/T polymorphism and comprised 622 patients and 712 controls (Table 1).…”

Section: Studies Included In the Meta-analysismentioning

confidence: 99%

“…Based on their functional significance, the roles of IL-6 −174 G/C, IL-6 −634 G/C, and IFN-γ +874 A/T polymorphisms in RPL susceptibility have been examined, with conflicting results [14][15][16][17][18][19][20][21][22][23][24][25][26][27][28]. This disparity may have been caused by small sample sizes, low statistical power, ethnic variability between studies, and/or clinical heterogeneity.…”

Section: Introductionmentioning

confidence: 99%

Association between IL-6 −174 G/C, IL-6 −634 G/C, and IFN-γ +874 A/T polymorphisms and susceptibility to recurrent pregnancy loss: a meta-analysis

Lee

Choi

2015

J Assist Reprod Genet

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Objective The aim of this study was to determine whether interleukin-6 (IL-6) −174 G/C, IL-6 −634 G/C, and interferon-γ (IFN-γ) +874 A/T polymorphisms are associated with susceptibility to recurrent pregnancy loss (RPL). Methods We conducted a literature search using PubMed and EMBASE databases and performed a meta-analysis using fixed-or random-effects models. Results A total of 15 articles met the study inclusion criteria. When all study subjects were considered together, metaanalysis showed no association between RPL and the IL-6 −174 GG+GC genotype (odds ratio [OR]=0.794, 95 % confidence interval [CI]=0.542-1.163, p=0.236). However, stratification of the data by ethnicity indicated an association between this genotype and RPL in non-Caucasians (OR=0.528, 95 % CI=0.302-0.925, p=0.028), but not in Caucasian populations. Moreover, meta-analysis revealed an association between RPL and the IL-6 −634 GG+GC genotype in all study subjects (OR=0.556, 95 % CI=0.383-0.806, p=0.002), while stratification by ethnicity revealed a negative association between this genotype and RPL in Asian (OR=0.545, 95 % CI= 0.371-0.800, p=0.002) but not Middle Eastern populations. Furthermore, a relationship between the IFN-γ +874 A allele and RPL was identified in non-Caucasians (OR=1.403, 95 % CI=1.133-1.734, p=0.002), but not in Caucasians.Conclusions This meta-analysis demonstrates that IL-6 −174 G/C, IL-6 −634 G/C, and IFN-γ +874 A/T polymorphisms are associated with susceptibility to RPL, particularly in nonCaucasians.

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Association between cytokine polymorphisms and recurrent pregnancy loss: A review of current evidence

Stavros,

Panagopoulos,

Machairiotis

et al. 2024

Intl J Gynecology & Obste

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Cytokines are a type of protein that play an important role in the immune response and can also affect many physiological processes in the body. Cytokine polymorphisms refer to genetic variations or mutations that occur within the genes that code for cytokines, which may affect the level of cytokine production and function. Some cytokine polymorphisms have been associated with an increased risk of developing certain diseases, while others may be protective or have no significant effect on health. In recent years, the role of cytokine polymorphisms in the development of recurrent pregnancy loss (RPL) has been studied. RPL or miscarriage is defined as the occurrence of two or more consecutive pregnancy losses before the 20th week of gestation. There are diverse causes leading to RPL, including genetic, anatomical, hormonal, and immunological factors. With regard to cytokine polymorphisms, a few of them have been found to be associated with an increased risk of RPL, for instance, variations in the genes that code for interleukin‐6, tumor necrosis factor‐alpha, and interleukin‐10. The exact mechanisms by which cytokine polymorphisms affect the risk of recurrent miscarriage are still being studied, and further research is essential to fully understand this complex condition. This brief review aims to summarize the recent literature on the association between cytokine polymorphisms and RPL.

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Cytokine Gene Polymorphisms in Recurrent Pregnancy Loss of Unknown Cause

Abstract: This finding would support the concept of involvement of IFN-gamma +874 A --> T in the pathogenesis of RPL of unknown cause in the Caucasian Argentine population.

Cited by 80 publications

References 27 publications

Immunogenetic contributions to recurrent pregnancy loss

Immunogenetic contributions to recurrent pregnancy loss

Association between IL-6 −174 G/C, IL-6 −634 G/C, and IFN-γ +874 A/T polymorphisms and susceptibility to recurrent pregnancy loss: a meta-analysis

Association between cytokine polymorphisms and recurrent pregnancy loss: A review of current evidence

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