The relevance of IL-1β and IL-1RN gene polymorphisms in the etiology of preterm delivery in the population of Polish women

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-1β 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-1β 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.

MTHFR genetic polymorphism and the risk of intrauterine fetal death in Polish women

Objectives: To evaluate the role of MTHFR genetic variants in the etiology of intrauterine fetal death in the second part of pregnancy at women from Polish population.  Material and methods: A case-control study was performed on a 76 women with a positive history of at least one in- trauterine fetal death after 22 gestational week and 400 healthy controls. The MTHFR genotyping for polymorphic sites 667C > T, 1298A > C, 1793G > A was determined by polymerase chain reaction/restriction fragment length polymorphism (PCR/RFLP) method.  Results: For 1298A > C polymorphism, no statistically significant higher frequency of AA vs. AC+CC genotype was observed in the IUFD group 67.1 % vs. 55.2% in the control group (OR = 0.61, p = 0.05, pcorr = 0.15). We observed overrepresentation of three-locus haplotype CCG (p = 0.20; pcorr = 0.56) and two-locus haplotype CC (p = 0.17; pcorr = 0.48) in the IUFD group compared to controls.  Conclusions: There was no observed relationships in genotype frequency of MTHFR 677C > T and 1793G > A variants, however 1298A > C showed a slightly higher but statistically insignificant prevalence in IUFD compared to the controls in Polish population. Further studies on a larger population are needed.

Genetic variants of progesterone receptor in etiology of preterm delivery

Objectives:  Preterm delivery (PTD) accounts for around 11% of pregnancies worldwide. Unfortunately, no diagnostic indicator, specific mechanism or genetic predisposition has yet been identified. One of the hypotheses suggest local or functional progesterone decrease as a potential reason for preterm uterine contractions leading to preterm delivery. It is believed that any change in progesterone receptor DNA may be crucial for higher risk of preterm delivery due to abnormal response to prostaglandins, normally inhibited by properly built progesterone. The aim of this study was to determine whether there is an association between progesterone gene polymorphisms (PROGINS and +331G/A) and preterm birth. Material and methods: A total of 230 women were enrolled, including 115 cases of preterm deliveries (between 22 and 36 weeks of gestation) and 115 healthy mothers of full-term infants. Genomic DNA was isolated from the blood sample. Polymerase chain reaction (PCR) amplification was carried out in a final volume of 25µL. Genotyping was assayed by PCR. Statistical analysis of the results was conducted with p < 0.05 accepted as statistically significant. Results: For both PROGINS (Alu ins/del) and +331G/A (rs10895068) polymorphisms were equally frequent in case and control group. The prevalence of PGR alleles in both groups was also comparable. Conclusions: The results of our study showed no association between progesterone gene polymorphisms (PROGINS and +331G/A) and risk of preterm delivery. Identifying mechanisms to prolong the length of gestation, particularly in women at risk for preterm delivery, will improve both maternal and fetal outcomes. 

FokI vitamin D receptor polymorphism as a protective factor in intrahepatic cholestasis of pregnancy

Objectives: Intrahepatic cholestasis in pregnancy (ICP) is a pregnancy-specific liver disorder. Its etiology is not fully understood. Increasing evidence indicates the important role of vitamin D and the vitamin D receptor (VDR) in this disorder. The presence of polymorphic variants in the VDR gene could influence its activity and susceptibility to ICP development. The goal of the study was to investigate the role of four genetic polymorphisms of the VDR gene — Fok (rs731236), Bsm (rs1544410), Apa (rs7975232), and Taq (rs731236) — in the etiology of ICP in Polish women. Material and methods: Ninety-eight women with confirmed ICP and 215 healthy pregnant women as a control group were recruited to the study. We examined four SNPs of the VDR gene: BsmI (rs7975232), TaqI (rs1544410), ApaI (rs228570), FokI (rs731236). Genotyping was performed using the PCR/RFLP method. Results: We observed higher frequency (borderline significant) of the Ff-ff genotypes containing at least one mutated allele of the VDR FokI polymorphism in the control group compared to the ICP group (p = 0.045, OR = 1.71, 95% CI 1.01–2.88). The frequency of the mutated f allele was slightly higher in controls (49.1%) than in the ICP group (43.4%) (OR = 1.26, 95% CI 0.90–1.77), but the difference was not statistically significant (p = 0.196). Conclusions: Our results showed that the maternal VDR FokI polymorphism could play a protective role in ICP development and probably modulate the risk of ICP occurrence in pregnant women in the Polish population. In the future, to confirm these observations, research in larger, ethnically stratified and clinically analyzed groups is necessary