The significance of TNF-alpha gene polymorphisms in preterm delivery.

Abstract

Nowadays the strong genetic background of preterm delivery (PTD) in connection with immune answer has been indicated. The purpose of the study was the assessment of frequency of TNF-alpha -238G>A, -308G>A, -376G>A gene polymorphisms in the etiology of preterm delivery The study group consisted of 150 women with PTD (22+0 - 36+6 gw.), the controls of 150 women who delivered at term (> 37 gw). PTD group was divided into subgroups: a/delivery between 22-28 gw, b/28-32 gw., and c/32-36+6 gw. Genetic analysis was performed by PCR/RLFP method. Overrepresentation of -238GA genotype (12.7 vs. 4.7%, p = 0.011) and -238A allele (7.7 vs. 2.3%, p = 0.002) in PTD group has been observed. In PTD 28-32 gw. subgroup, higher frequency of -238GA genotype (31.6 vs. 4.7%, p = 0.00095), and mutated -238A allele (21.1 vs. 2.3%, p = 0.00004) was noted. Moreover in PTD 28-32 gw. subgroup we have noted higher presence of heterozygous -376GA genotype (10.5 vs. 1.3%, p = 0.063) and mutated -376A allele (5.3 vs. 0.7%, p = 0.064). Analysis of TNF-alpha polymorphisms co-occurrence showed statistically significant overrepresentation of genotypes containing mutated -238A allele in PTD group (-238GA/-308GG/-376GG: 8.0 vs. 2.7%, p = 0.035). Haplotype analysis revealed statistically significant difference between PTD and controls in the incidence of -376G/-308G/-238A haplotype containing mutated -238A allele (0.063067 vs. 0.016634, p = 0.030). The study indicated the strong association of mutated -238A allele of TNF-alpha gene with increased risk of PTD. Analysis of genotypes and alleles prevalence in PTD women divided according to gestational age suggests the possible role of mutated variants of -238G>A and -376G>A TNF-alpha polymorphisms in Polish women delivering between 28 and 32 gw.