Fine-Mapping an Association of FSHR with Preterm Birth in a Finnish Population

Chun, Sung; Plunkett, Jevon; Teramo, Kari; Muglia, Louis J.; Fay, Justin C.

doi:10.1371/journal.pone.0078032

Cited by 15 publications

(11 citation statements)

References 56 publications

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“…One SNP in FSHR gene (rs6165) showed a P value <0.05 in the gestation age <32-wk group and PPROM group, but did not reach formal levels of significance once corrected for multiple comparisons. Notably our results did not replicate the previously described associations of FSHR polymorphisms and PTB (19,20). In addition, SNPs in SERPINH1 did not show an association with PPROM cases as shown previously (21).…”

Section: Resultscontrasting

confidence: 99%

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Polymorphisms in NR5A2, gene encoding liver receptor homolog-1 are associated with preterm birth

et al. 2016

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Background. Preterm birth (PTB) is a major cause of neonatal mortality and morbidity. There is strong evidence of genetic susceptibility. Objective of the study was to identify genetic variants contributing to PTB. Methods. Genotyping was performed for 24 SNPs in 4 candidate genes (NR5A2, FSHR, FOXP3, SERPINH1). Genotyping was completed on 728 maternal triads (mother & maternal grandparents of a preterm infant). Data were analyzed with Family Based Association Test. Results. For all maternal triads rs2737667 of NR5A2 showed significant association at P= 0.02. When stratifying by gestational age three SNPs in NR5A2 had p values <0.05 in the <32 weeks gestational age group (rs12131233, p=0.007; rs2737667, p=0.04; rs2816949, p=0.02). When PPROM cases were excluded rs2737667 of NR5A2 showed the strongest association with a p value <0.0002. This association remained significant after correction for multiple testing. Conclusions. This study suggests a potential association between intronic SNPs in the NR5A2 gene and PTB. NR5A2 gene encodes for the Liver receptor homolog 1(LRH1) protein, which plays a critical role in regulation of cholesterol metabolism, steroidogenesis and progesterone synthesis. These findings suggest NR5A2 may be important in the pathophysiology of PTB and exploring of non-coding regulators of NR5A2 is warranted.

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Section: Resultscontrasting

confidence: 99%

“…LRH1 has been shown to play an important role in establishing and sustaining pregnancy in animal models (18). Polymorphisms in FSHR encoding follicle-stimulating hormone receptor have been found to be associated with PTB in a Finnish as well as an African-American population (19,20). Dysregulation of FSHR may contribute to early uterine contractility.…”

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confidence: 99%

Polymorphisms in NR5A2, gene encoding liver receptor homolog-1 are associated with preterm birth

et al. 2016

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“…Further examination revealed many common variants in FSHR and an association of noncoding SNP haplotypes with both preterm birth risk and protection Chun et al 2013). The putative causal variants in both haplotypes are predicted to alter binding site affinity for transcription factors with potential roles in the initiation of parturition (Chun et al 2013). Although these findings were somewhat restricted to the examined Finnish cohort, they point to additional candidate genes and pathways for study in more broad populations.…”

Section: Selective Pressures and Adaptive Evolution In Human Pregnancmentioning

confidence: 94%

“…Suggested function in the uterus and cervix and an influence on PR isoform abundance in mice (Danilovich et al 2002), provide further www.perspectivesinmedicine.org possibilities for its potential involvement in normal birth timing and preterm birth risk. Further examination revealed many common variants in FSHR and an association of noncoding SNP haplotypes with both preterm birth risk and protection Chun et al 2013). The putative causal variants in both haplotypes are predicted to alter binding site affinity for transcription factors with potential roles in the initiation of parturition (Chun et al 2013).…”

Section: Selective Pressures and Adaptive Evolution In Human Pregnancmentioning

confidence: 99%

Genomics of Preterm Birth

Swaggart

Pavličev

Muglia

2015

Cold Spring Harbor Perspectives in Medicine

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The molecular mechanisms controlling human birth timing at term, or resulting in preterm birth, have been the focus of considerable investigation, but limited insights have been gained over the past 50 years. In part, these processes have remained elusive because of divergence in reproductive strategies and physiology shown by model organisms, making extrapolation to humans uncertain. Here, we summarize the evolution of progesterone signaling and variation in pregnancy maintenance and termination. We use this comparative physiology to support the hypothesis that selective pressure on genomic loci involved in the timing of parturition have shaped human birth timing, and that these loci can be identified with comparative genomic strategies. Previous limitations imposed by divergence of mechanisms provide an important new opportunity to elucidate fundamental pathways of parturition control through increasing availability of sequenced genomes and associated reproductive physiology characteristics across diverse organisms.

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“…Na população afro-americana, com 79 casos e 171 controles, também se observaram diferenças significativas entre tais frequências 7 . A frequência do alelo de risco T reportada em gestantes finlandesas com parto prematuro foi de 41,7%, superior a das pacientes com a mesma condição neste estudo 22 . Deve-se considerar que essas populações apresentam ancestralidade e características genéticas distintas.…”

Section: Discussionunclassified

Suscetibilidade à prematuridade: investigação de fatores comportamentais, genéticos, médicos e sociodemográficos

Hackbarth¹,

Ferreira²,

Carstens³

et al. 2015

Rev. Bras. Ginecol. Obstet.

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ResumoOBJETIVO: Investigar a associação entre fatores de risco genéticos, comportamentais, biológicos e médicos e a ocorrência da prematuridade. MÉTODOS: Realizou-se estudo retrospectivo do tipo caso-controle. A técnica de reação em cadeia da polimerase em tempo real foi utilizada para analisar a influência dos polimorfismos rs12473815 do gene codificante para o receptor do hormônio folículo estimulante (FSHR) e rs1942836 do gene codificante para o receptor da progesterona (PGR). A avaliação dos outros fatores de risco se deu por meio da aplicação de questionários validados ou especificamente desenvolvidos e análise de dados em prontuário eletrônico. Foram incluídas 157 gestantes (45 casos com gestação <37 semanas e 112 controles com gestação >37 e ≤42 semanas). RESULTADOS: Os genótipos CT do polimorfismo rs12473815 e TC e CC do polimorfismo rs1942836 mostraram-se associados a uma maior chance de desenvolver parto prematuro. Observou-se associação entre o nascimento prematuro e a ingestão alcoólica quando o consumo ocorreu em duas ou mais ocasiões mensais. O baixo índice de massa corporal pré-gestacional se mostrou preditor do nascimento prematuro espontâneo, enquanto o elevado índice de massa corporal reduziu a sua probabilidade. CONCLUSÕES: Os resultados encontrados sugerem que a ingestão alcoólica excessiva, o baixo índice de massa corporal pré-gestacional e os alelos de risco dos polimorfismos rs12473815 e rs1942836 dos genes FSHR e PGR, respectivamente, influenciam a ocorrência de nascimento prematuro. Abstract PURPOSE:To investigate the association between genetic, behavioral, biological and medical risk factors and the occurrence of preterm birth. METHODS: A retrospective case-control study was conducted. The real-time polymerase chain reaction was used to analyze the influence of the rs12473815 polymorphism of the follicle stimulating hormone receptor gene (FSHR) and the rs1942836 polymorphism of the progesterone receptor gene (PGR). Other proposed risk factors were assessed using validated or specifically developed questionnaires and analysis of electronically recorded medical data. A total of 157 patients were included (45 cases who went into labor before 37 weeks of pregnancy and 112 controls who went into labor after 37 and before 42 weeks of pregnancy). RESULTS: The genotypes CT of rs12473815 and CT and CC of rs1942836 were associated with a higher chance of premature delivery. There was an association between preterm birth and alcohol intake when consumption occurred 2 or more times per month. Low pre-pregnancy body mass index was a predictor of spontaneous preterm birth, while high body mass index reduced this likelihood. CONCLUSIONS: The results suggest that excessive alcohol intake, a low level of pre-pregnancy body mass and the risk alleles of rs12473815 and rs1942836 polymorphisms of the FSHR and PGR genes, respectively, influence the occurrence of preterm birth.

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Fine-Mapping an Association of FSHR with Preterm Birth in a Finnish Population

Cited by 15 publications

References 56 publications

Polymorphisms in NR5A2, gene encoding liver receptor homolog-1 are associated with preterm birth

Polymorphisms in NR5A2, gene encoding liver receptor homolog-1 are associated with preterm birth

Genomics of Preterm Birth

Suscetibilidade à prematuridade: investigação de fatores comportamentais, genéticos, médicos e sociodemográficos

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