The significance of TNF-α gene polymorphisms in preterm delivery

Abstract

Introduction: 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-α -238G>A, -308G>A, -376G>A gene polymorphisms in the etiology of preterm delivery. Material and methods: 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. Results: 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-α 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).Conclusion: The study indicated the strong association of mutated -238A allele of TNF-α 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-α polymorphisms in Polish women delivering between 28 and 32 gw.