Impact of genetic variation of tumor necrosis factor-alpha on gestational hypertension

The mechanisms responsible for the pathogeneses of gestational hypertension and preeclampsia are unclear. Tumor necrosis factor-alpha (TNF-alpha) is a pro-inflammatory Th(1)-type cytokine. TNFA gene is located in the human leukocyte antigen (HLA) class III region of the major histocompatibility complex (MHC) on chromosome 6. The high TNF-alpha mRNA expression may be associated with the TNF2 (A) allele, which is the polymorphism of TNF-alpha at position -308 in promoter region. This study assessed whether the TNF2 (A) allele at position -308 plays a role in the alteration of blood pressure (BP) and urinary protein excretion during pregnancy.

The original prospective cohort study comprised 1623 pregnant women from January 2000 to October 2001. The G/A polymorphism was done by restriction fragment length polymorphism (RFLP) analysis with Nco I enzyme.

The distributions of the G/A polymorphism of TNF-alpha in the promoter region at position -308 were wild-type 72.4% and variant 27.6%, respectively. The frequency of TNF2 (A) allele was approximately 0.15 for Caucasian pregnant women in the study. It was not significantly different in the distributions of genotypes and G/A allele frequencies among the three groups of pregnant women with gestational hypertension, preexisting hypertension and normal blood pressure (P > 0.05). The maternal blood pressure in the third trimester was significantly higher in the group of women possessing the TNF2 (A) allele compared to homozygous for the TNF1 (G) allele (systolic BP, P < 0.01 and diastolic BP, P < 0.05). The elevated blood pressure in the TNF2 (A) group was accompanied by higher urinary protein excretion in the third trimester (P < 0.05). The blood pressure and urinary protein excretion did not change apparently between the two groups in the first and second trimesters (P > 0.05).

Maternal TNF2 (A) allele of TNF-alpha promoter region at position -308 could play a role in the alteration of blood pressures and/or enhancement of urinary protein excretion during pregnancy, and might play an important role in the development of both gestational hypertension and preeclampsia.