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Association between tumor necrosis factor (TNF)-alpha G-308A gene polymorphism and preeclampsia complicated by severe fetal growth restriction.
Clin Chim Acta. 2008 Jun; 392(1-2):52-7.CC

Abstract

BACKGROUND

Preeclampsia and HELLP (hemolysis, elevated liver enzymes, and low platelet count) syndrome are multifactorial disorders with genetic and environmental components. Given that the tumor necrosis factor (TNF)-alpha G-308A single nucleotide polymorphism (SNP) affects TNF-alpha gene transcription and that preeclampsia and HELLP syndrome are characterized by a shift towards a Th1-type maternal immune response with increased TNF-alpha production, the aim of the current study was to investigate whether this SNP is associated with preeclampsia and HELLP syndrome in a Caucasian population from Hungary. Additionally, we aimed to examine whether TNF-alpha G-308A polymorphism can influence the risk for fetal growth restriction in preeclamptic patients, which issue none of the earlier studies dealt with.

METHODS

In a case-control study, we analyzed blood samples from 140 preeclamptic patients, 69 patients with HELLP syndrome and 144 normotensive, healthy pregnant women using the polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP) method. We performed also a meta-analysis with our results and those of 8 previously published studies.

RESULTS

There were no significant differences in the genotype and allele frequencies of the TNF-alpha G-308A polymorphism between preeclamptic patients and normotensive, healthy pregnant women. However, the mutant (TNF2 or A) allele occurred significantly more frequently in preeclamptic patients with IUGR than in those without IUGR (18.5% versus 7.1%, p=0.003). In addition, the frequency of the mutant allele carriers was significantly higher among preeclamptic patients with IUGR compared to those without IUGR (30.6% versus 12.8%, p=0.010). The mutant allele carriers were found to have an increased risk of severe IUGR-complicated preeclampsia, which was independent of maternal age, prepregnancy BMI and primiparity (odds ratio (OR): 2.89, 95% confidence interval (CI): 1.16-7.22, p=0.023; adjusted OR: 2.78, 95% CI: 1.04-7.45, p=0.042). Nevertheless, no significant differences were detected in the genotype and allele frequencies of the TNF-alpha G-308A polymorphism between patients with HELLP syndrome and control subjects. In the meta-analysis, no association was observed between this SNP and preeclampsia (summary OR: 0.956, 95% CI: 0.693-1.319).

CONCLUSIONS

Although the meta-analysis demonstrated a lack of an overall association between TNF-alpha G-308A polymorphism and preeclampsia, our results suggest a role of this SNP in the risk of severe IUGR-complicated preeclampsia. However, further studies are required with a larger sample size to confirm our findings.

Authors+Show Affiliations

1st Department of Obstetrics and Gynecology, Semmelweis University, Budapest, Hungary. molvarec@freemail.huNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Meta-Analysis
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

18396154

Citation

Molvarec, Attila, et al. "Association Between Tumor Necrosis Factor (TNF)-alpha G-308A Gene Polymorphism and Preeclampsia Complicated By Severe Fetal Growth Restriction." Clinica Chimica Acta; International Journal of Clinical Chemistry, vol. 392, no. 1-2, 2008, pp. 52-7.
Molvarec A, Jermendy A, Nagy B, et al. Association between tumor necrosis factor (TNF)-alpha G-308A gene polymorphism and preeclampsia complicated by severe fetal growth restriction. Clin Chim Acta. 2008;392(1-2):52-7.
Molvarec, A., Jermendy, A., Nagy, B., Kovács, M., Várkonyi, T., Hupuczi, P., Prohászka, Z., & Rigó, J. (2008). Association between tumor necrosis factor (TNF)-alpha G-308A gene polymorphism and preeclampsia complicated by severe fetal growth restriction. Clinica Chimica Acta; International Journal of Clinical Chemistry, 392(1-2), 52-7. https://doi.org/10.1016/j.cca.2008.03.009
Molvarec A, et al. Association Between Tumor Necrosis Factor (TNF)-alpha G-308A Gene Polymorphism and Preeclampsia Complicated By Severe Fetal Growth Restriction. Clin Chim Acta. 2008;392(1-2):52-7. PubMed PMID: 18396154.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Association between tumor necrosis factor (TNF)-alpha G-308A gene polymorphism and preeclampsia complicated by severe fetal growth restriction. AU - Molvarec,Attila, AU - Jermendy,Agnes, AU - Nagy,Bálint, AU - Kovács,Margit, AU - Várkonyi,Tibor, AU - Hupuczi,Petronella, AU - Prohászka,Zoltán, AU - Rigó,János,Jr Y1 - 2008/03/18/ PY - 2008/01/23/received PY - 2008/03/12/revised PY - 2008/03/12/accepted PY - 2008/4/9/pubmed PY - 2008/8/1/medline PY - 2008/4/9/entrez SP - 52 EP - 7 JF - Clinica chimica acta; international journal of clinical chemistry JO - Clin Chim Acta VL - 392 IS - 1-2 N2 - BACKGROUND: Preeclampsia and HELLP (hemolysis, elevated liver enzymes, and low platelet count) syndrome are multifactorial disorders with genetic and environmental components. Given that the tumor necrosis factor (TNF)-alpha G-308A single nucleotide polymorphism (SNP) affects TNF-alpha gene transcription and that preeclampsia and HELLP syndrome are characterized by a shift towards a Th1-type maternal immune response with increased TNF-alpha production, the aim of the current study was to investigate whether this SNP is associated with preeclampsia and HELLP syndrome in a Caucasian population from Hungary. Additionally, we aimed to examine whether TNF-alpha G-308A polymorphism can influence the risk for fetal growth restriction in preeclamptic patients, which issue none of the earlier studies dealt with. METHODS: In a case-control study, we analyzed blood samples from 140 preeclamptic patients, 69 patients with HELLP syndrome and 144 normotensive, healthy pregnant women using the polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP) method. We performed also a meta-analysis with our results and those of 8 previously published studies. RESULTS: There were no significant differences in the genotype and allele frequencies of the TNF-alpha G-308A polymorphism between preeclamptic patients and normotensive, healthy pregnant women. However, the mutant (TNF2 or A) allele occurred significantly more frequently in preeclamptic patients with IUGR than in those without IUGR (18.5% versus 7.1%, p=0.003). In addition, the frequency of the mutant allele carriers was significantly higher among preeclamptic patients with IUGR compared to those without IUGR (30.6% versus 12.8%, p=0.010). The mutant allele carriers were found to have an increased risk of severe IUGR-complicated preeclampsia, which was independent of maternal age, prepregnancy BMI and primiparity (odds ratio (OR): 2.89, 95% confidence interval (CI): 1.16-7.22, p=0.023; adjusted OR: 2.78, 95% CI: 1.04-7.45, p=0.042). Nevertheless, no significant differences were detected in the genotype and allele frequencies of the TNF-alpha G-308A polymorphism between patients with HELLP syndrome and control subjects. In the meta-analysis, no association was observed between this SNP and preeclampsia (summary OR: 0.956, 95% CI: 0.693-1.319). CONCLUSIONS: Although the meta-analysis demonstrated a lack of an overall association between TNF-alpha G-308A polymorphism and preeclampsia, our results suggest a role of this SNP in the risk of severe IUGR-complicated preeclampsia. However, further studies are required with a larger sample size to confirm our findings. SN - 0009-8981 UR - https://www.unboundmedicine.com/medline/citation/18396154/Association_between_tumor_necrosis_factor__TNF__alpha_G_308A_gene_polymorphism_and_preeclampsia_complicated_by_severe_fetal_growth_restriction_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0009-8981(08)00120-4 DB - PRIME DP - Unbound Medicine ER -