ABSTRACT
OBJECTIVES: Preterm delivery (PTD) is one of the important challenges for perinatal medicine due to prematurity and associated complications. The mechanisms leading to the PTD occurrence are not fully clarified and it is assumed that PTD is a complex phenomenon caused by many different pathophysiological factors. Nowadays, an important role is attributed to genetic determinants of PTD, pointing to possible relevance of polymorphic variants of candidate genes to participate in the etiology of PTD. The aim of the study was to assess the relevance of +3953C > T IL-1ß and 86 bp VNTR IL-1RN gene polymorphisms in the etiology of PTD in Polish women. MATERIAL AND METHODS: Study group consisted of 150 women (mean age 29.2 ± 5.6 years, mean weeks of gestational age 33.7 ± 2.8 gw.) with preterm delivery (22 + 0 - 36 + 6 gw.). To the control group 150 healthy pregnant women (mean age 29.0 ± 3.7 years, mean weeks of gestational age 39.3 ± 1.2 gw.) who delivered > 37 gw. were enrolled. All investigated polymorphisms were analyzed by polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP). RESULTS: The interesting observation was the notice of overrepresentation of 2/2 genotype of IL-1RN gene in the control group (8.0 vs. 3.3%, p = 0.06) and 2 allele in the control group (25.0 vs. 20.0%, p = 0.07). CONCLUSIONS: The +3953C > T polymorphism of IL-1ß gene probably is not connected with the risk of preterm delivery. The study results points to the possible modulating effect of mutated IL-1RN* 2 allele (86 bp VNTR polymorphism) of IL-1RN gene in decreased risk of preterm delivery.
Subject(s)
Interleukin 1 Receptor Antagonist Protein/genetics , Interleukin-1beta/genetics , Polymorphism, Genetic/genetics , Premature Birth/epidemiology , Premature Birth/genetics , Adult , Case-Control Studies , Female , Genetic Predisposition to Disease , Humans , Infant, Premature , Poland/epidemiology , Pregnancy , Young AdultABSTRACT
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-alpha -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-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). CONCLUSION: 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.