The association between polymorphism of TNF-α gene and hypertensive disorder complicating pregnancy

Abstract

To study whether the development of hypertensive disorder complicating pregnancy is associated with −308G→A, −850C→T mutation at promoter of TNF-α gene, the −308G→A, −850C→T polymorphism was examined in patients and healthy pregnant women by PCR-RFLP technique. The frequencies of genotype and allele were compared between the two groups. The results showed that with −308G→A polymorphism distribution, the allele frequency of TNF2 and the frequency of the genotype TNF2/1 in the patient group was significantly higher in the patient group than in control group (P<0.05). A significant difference in genotype distribution of −850C→T polymorphism was observed between the two groups. The allele frequencies of T in patient group was higher in the control group as compared with the patient group. The frequencies of CT and TT genotypes were lower in the patient group. It is concluded that the TNF2 allele of −308 is associated with the occurrence of hypertensive disorder complicating pregnancy, while T allele of −850 may be the protective factor against the development of the disease. TNF2/1 CC may be susceptibility genotype of hypertensive disorder complicating pregnancy.

Keywords

TNF-α / hypertensive disorder complicating pregnancy / gene polymorphism

References

[1] GouW. L.. hypertensive disorder complicating pregnancy. Le Jie, Gynecology and Obstetrics (Chinese), 20045th ed.Beijing, People’s Medical Publishing House: 97-104

[2] SakaoS., TatsumiK., IgariH., et al.. Association of tumor necrosis factor alpha gene promoter polymorphism with the presence of chronic obstructive pulmonary disease. Am J Respir Crit Care Med, 2001, 163: 420-422

[3] KatoT., HondaM., KuwataS., et al.. Novel Polymorphism in the Promoter Region of the Tumor Necrosis Factor Alpha Gene: No Association With Narcolepsy. Am J Med Genet (Neuropsychiatric Genet), 1999, 88: 301-304

[4] RinehartB. K., TerroneD. A., Lagoo-DeenadayalanS., et al.. Expression of the placental cytokines tumor necrosis factor alpha, interleukin 1 beta, and interleukin 10 is increased in preeclampsia. Am J Obstet Gynecol, 1999, 181: 915-920

[5] PangZ. J., XingF. Q.. Comparative study on the expression of cytokine-receptor genes in normal and preeclamptic human placentas using DNA microarrays. J Perinat Med, 2003, 31: 153-162

[6] Anim-NyameN., GambleJ., SoorannaS. R., et al.. Microvascular permeability is related to circulating levels of tumour necrosis factor-alpha in pre-eclampsia. Cardiovasc Res, 2003, 58: 162-169

[7] KupfermincM., PeacemanA. M., WigtonT. R., et al.. Tumor necrosis factor is elevated in plasma and amniotic fluid of patients with severe preeclampsia. Am J Obstet Gynecology, 1994, 170: 1752-1759

[8] HaegerM., UnanderM., AnderssonB., et al.. Increased release of tumor necrosis factor-αin preeclamptic patients with and without the HELLP syndrome. BJOG, 1994, 101: 1081-1082

[9] WilsonA. G., di GiovineF. S., BlakemoreA. I., et al.. Single base polymorphism in the human tumour necrosis factor alpha (TNF alpha) gene detectable by NcoI restriction of PCR product. Hum Mol Genet, 1992, 1: 353

[10] HeiskanenJ., RomppanenE. L., HiltunenM., et al.. Polymorphism in the Tumor necrosis factor-α gene in women with preeclampsia. J Assist Reprod Genet, 2002, 19: 220-223

[11] KroegerK. M., CarvilleK. S., AbrahamL. J.. The-308 tumor necrosis factor-alpha promoter polymorphism effects transcription. Mol Immunol, 1997, 34: 391-339

[12] LouisE., FranchimontD., PrionA., et al.. Tumour necrosis factor (TNF) gene polymorphism influences TNF-alpha production in lipopolysaccharide (LPS)-stimulated whole blood cell culture in healthy humans. Clin Exp Immunol, 1998, 113: 401-406