Genetic associations of relaxin: preterm birth and premature rupture of fetal membranes

Abstract

Objectives Relaxin H2 (RLN2) is a systemic hormone (sRLN) produced by the corpus luteum, whereas decidual (dRLN) only acts locally. Elevated sRLN is associated with spontaneous preterm birth (sPTB) and elevated dRLN with preterm premature rupture of membranes (PPROM). Associations were sought between single nucleotide polymorphisms (SNPs) in the RLN2 promoter with levels of dRLN and sRLN in Filipino patients with sPTB, PPROM or normal term delivery. Study Design Stringent selection of women with sPTB (n=20) or PPROM (n=20) and term controls (n=20) was made from over 8,000 samples from Filipino patients delivered at 34–36 weeks gestation. Twelve SNPs were genotyped on maternal blood with exclusion of nine based on high linkage disequilibrium (LD) or being the same as in the control population. Quantitative immunocytochemistry on parietal decidual tissue was performed (n=60) and sRLN measured by ELISA in a subset of patients (n=21). Results SNP rs4742076 was significantly associated with PPROM (p<0.001) and increased expression of dRLN (p<0.001). The genotype TT had increased dRLN in PPROM (p<0.05). SNP rs3758239 was significantly associated with both PPROM and sPTB (p<0.01), and genotype AA had increased dRLN expression (p<0.05). The sRLN showed a trend of higher levels in PPROM and sPTB, but was not significant. Conclusions SNP rs4742076 in the RLN2 promoter was associated with increased dRLN expression and PPROM while SNP rs3758239 was associated with both PPROM and sPTB in these Filipino patients. Specific homozygous genotypes were identified for both SNPs and were shown to be associated with increased dRLN tissue expression.

Insights from physiology into myometrial function and dysfunction

“…; Rocha et al . ) and, of particular interest, oxytocin pathway genes. The availability of oxytocin to its receptor is dependent on serum levels of leucyl/cystinyl aminopeptidase, an enzyme that hydrolyses and inactivates the hormone.…”

A Retrospective Comparison of Antibiotic Regimens for Preterm Premature Rupture of Membranes

“…The etiology is often unknown but may be related to infection (3–5), membrane dysfunction on a molecular level (6, 7), genetic variation (8, 9), or a combination of factors (10). Treatment with antibiotics in the absence of labor has been shown to decrease the frequency of chorioamnionitis (11), prolong latency, and decrease fetal and neonatal complications (12–14).…”

Prognostic possibilities of relaxin as a marker of preterm birth

“…Наличие связи между гиперрелаксинемией во время беременности и риском преждевре-менных родов в дальнейшем было подтвержде-но и другими исследователями [11,13,[29][30][31]. Широкий спектр биологических действий ре-лаксина позволяет небезосновательно полагать существование патофизиологической основы для реализации релаксин-индуцированного пути развития преждевременных родов [26].…”

“…Оценка полученных результатов показала, что у пациенток с наличием геноти-па AA SNP rs3758239 был высокий риск пре-ждевременных родов, начавшихся с излития околоплодных вод. А наличие генотипа ТТ ге-нотипа SNP rs4742076 ассоциировано с прежде-временными родами, которые начались как со спонтанной родовой деятельности, так и с прежде временного излития околоплодных вод [26]. (RLN1 -rs3758240, rs1322220, rs10481591, rs7048887, rs1575279; RLN2 -rs3758239, rs4742076, rs10115467; RLN3 -rs7248735).…”

“…Обнаружение генетической предрасполо-женности к преждевременным родам у жен-щин с определенными полиморфизмами в ге-нах релаксина является важным с точки зрения возможности оценки риска досрочного преры-вания беременности еще на этапе ее планиро-вания. Генетическое тестирование пациенток на наличие полиморфизмов в гене релаксина может помочь расширить меры профилактики преждевременных родов и снизить частоту их наступления [26,40].…”