Prostanoid DP receptor (PTGDR) variants in mothers with post-coital associated preterm births: preliminary observations (original) (raw)
Related papers
Progesterone Receptor (PGR) gene polymorphism is associated with susceptibility to preterm birth
BMC Medical Genetics, 2015
Background: Preterm birth (PTB) is the major cause of death in newborn and the second major cause of death in children less than 5 years old worldwide. Genetic polymorphism has been implicated as a factor for the occurrence of preterm birth. The aim of this study is to evaluate whether polymorphism in the progesterone receptor (PGR) is associated with susceptibility to preterm birth. Methods: A total of 135 women with preterm and 532 women with term deliveries were genotyped for PGR gene polymorphisms (rs660149, rs471767, rs10895068) using Sequenom MassARRAY platform. Results: The G allele of PGR rs660149 polymorphism was significantly associated with susceptibility to PTB in the Malay women. The odds of G allele occurring among Malay women with preterm delivery was twice that of Malay women with term delivery (OR 2.3, 95 % CI (1.2-4.5, P = 0.011). Alternatively, no significant association was observed between PGR rs660149 polymorphisms and susceptibility to PTB in Chinese and Indian women. Conclusions: This study shows that variability in the occurrence of PTB across ethnicities in Malaysia is partly due to differences in genetic background. We therefore suggest that in addition to life style and environmental factors, genetic factor should be greatly considered in this population. Prior information on the genetic composition of women may help in the identification and management of women at risk of preterm birth complication.
Spontaneous preterm birth and single nucleotide gene polymorphisms: a recent update
BMC Genomics, 2016
Background: Preterm birth (PTB), birth at <37 weeks of gestation, is a significant global public health problem. Worldwide , about 15 million babies are born preterm each year resulting in more than a million deaths of children. Preterm neonates are more prone to problems and need intensive care hospitalization. Health issues may persist through early adulthood and even be carried on to the next generation. Majority (70 %) of PTBs are spontaneous with about a half without any apparent cause and the other half associated with a number of risk factors. Genetic factors are one of the significant risks for PTB. The focus of this review is on single nucleotide gene polymorphisms (SNPs) that are reported to be associated with PTB. Results: A comprehensive evaluation of studies on SNPs known to confer potential risk of PTB was done by performing a targeted PubMed search for the years 2007-2015 and systematically reviewing all relevant studies. Evaluation of 92 studies identified 119 candidate genes with SNPs that had potential association with PTB. The genes were associated with functions of a wide spectrum of tissue and cell types such as endocrine, tissue remodeling, vascular, metabolic, and immune and inflammatory systems. Conclusions: A number of potential functional candidate gene variants have been reported that predispose women for PTB. Understanding the complex genomic landscape of PTB needs high-throughput genome sequencing methods such as whole-exome sequencing and whole-genome sequencing approaches that will significantly enhance the understanding of PTB. Identification of high risk women, avoidance of possible risk factors, and provision of personalized health care are important to manage PTB.
American Journal of Medical Genetics Part A, 2007
Protease activated receptor 1 (PAR1), the thrombin receptor, is implicated in hemostasis, tissue remodeling, and is critical in early placentation. PAR1 polymorphisms that influence coagulation and adhesion molecule expression may compromise formation of a normal placenta, thereby resulting in adverse outcomes. This study is a prospective, case-control comparison of Israeli mother-neonate (singletons) pairs of complicated pregnancies: 33 preterm deliveries (PTDs), 20 preeclampsia (PE), and 28 idiopathic small for gestational age neonates (SGA) versus 98 pairs of uncomplicated singleton deliveries. PCR amplification identified polymorphisms in the 5 0 regulatory region of the PAR1 gene at [À1426 )], insertion at [À506 (I/D)], and IVS at [À14 (A/ T)]. We found that 15.2% mothers with PTD were heterozygous for [À1426] versus 3% in uncomplicated deliveries; however, maternal allele frequency was not significantly different between pregnancies complicated by PE or SGA versus uncomplicated pregnancies. Maternal allele frequencies for [À506] and [À14] polymorphisms were not significantly different between any of the study groups compared to the uncomplicated group. Haplotype analysis recapitulated the genotype pattern. Maternal homozygous allele frequency for each of the polymorphic variants was low (<2%) in all pregnancies, and equally distributed. Neonatal genotypes did not differ between groups and were not associated with adverse outcomes. Maternal heterozygous allele state for PAR1 polymorphism [À1426] and the haplotype with [À506 wild-type]/[À1426T]/[IVS-14A] is associated with PTD. ß 2007 Wiley-Liss, Inc.
A Possible Role for the PPARG Pro12Ala Polymorphism in Preterm Birth
Diabetes, 2007
The links between preterm birth, low birth weight, and adult vascular/metabolic morbidity remain unclear. Genetic susceptibility of babies related to these three conditions might contribute to this long-term association. We tested whether the Pro12Ala polymorphism of the peroxisome proliferator-activated receptor ␥ (PPARG) gene could play a role in birth weight and duration of gestation. We genotyped two independent cross-sectional studies from Northern Ireland (n ؍ 382 and 620). In combined populations, the PPARG Ala12 allele was associated (P ؍ 0.03) with lower birth weight, primarily caused by shorter gestational duration (P ؍ 0.04). The frequency of Ala12 allele carriers was higher (P ؍ 0.027) in the group of individuals born before term (35%, n ؍ 60) than in the group of individuals born at term (22%, n ؍ 942). The odds ratios (95% CI) of preterm birth for Ala12 allele carriers were 1.9 (1.1-3.4), P ؍ 0.022, and 4.2 (1.9-9.7), P ؍ 0.0006 (adjusted for sex, maternal age, and study), when considering 37 or 35 weeks of pregnancy as a threshold for preterm birth, respectively. Interestingly, the same allele was also associated with a moderate decreased risk of miscarriages in mothers. In conclusion, the PPARG Pro12Ala polymorphism might represent a genetic susceptibility factor for preterm birth and constitute a link between preterm birth and metabolic diseases later in life. Diabetes 56:494-498, 2007 RESEARCH DESIGN AND METHODS Populations. The Young Hearts (YH) project is a prospective study investigating the development of biological and behavioral risk factors for cardiovascular disease in an adolescent population in Northern Ireland. Details of the study design and sampling procedure have been presented elsewhere (6). Briefly, in 1989-1990, a 2% representative sample of school children aged 12 and 15 years in Northern Ireland (YH3, n ϭ 1,015) was collected. The original 12-year-old population was followed up in 1992-1993 (YH2) with complete data collected on 225 boys and 230 girls (90% response rate). Between 1997 and 1999, all original YH participants were invited to participate in the third screening phase (YH3, age 21-25 years, n ϭ 489), and a blood sample for DNA extraction was taken at that time. A further cross-sectional survey, the Young Hearts 2000 (YH2000), was carried out in 2000. Approximately 2,000 boys and girls aged 12 and 15 years (500 in each of the four age-sex groups) were recruited through postprimary schools. Details of the study design have been presented elsewhere (7). In Northern Ireland, birth records have been computerized since 1971 by the Department of Health and Social Services. Records concerning birth weight and length of gestation were available from this data system. Other perinatal information available included parity, parental age, number of miscarriages, and number of stillbirths. Genomic DNA and data on gestational duration and birth weight were available for 382 and 620 singleton births in YH3 and YH2000, respectively. The prevalence of preterm birth (before 37
Progesterone receptor genotype, family history, and spontaneous preterm birth
Obstetrics and gynecology, 2010
To examine whether women with a personal or family history of preterm birth are more likely to have genetic variation in the human progesterone receptor (hPR). Women with a singleton preterm birth at less than 37 weeks of gestation between 2002 and 2006 were identified from a prospectively collected clinical and biologic obstetric database (cases). Women in the control group were those with only term deliveries at or above 38 weeks of gestation. The Utah Population Database was queried for family history (first- or second-degree relative) of preterm birth. DNA was extracted from stored buffy coats and genotyped for six single nucleotide polymorphisms in the hPR. One hundred fifty-four patients (92 women in the preterm case group, 62 women in the term control group) were included. All were white or Hispanic. There were no statistical differences between white and Hispanic allele frequencies. Women in the preterm case group were more likely to carry the minor allele, G (minor allele f...
Pediatric Research, 2013
Clinical Investigation nature publishing group Background: The aim of this study was to replicate singlenucleotide polymorphism (SNP) associations with preterm birth (PTB; birth at <37 completed weeks of gestation) and synthesize currently available evidence using meta-analysis. Methods: Spontaneous PTB cases and controls were selected from an existing cohort. Candidate SNPs were taken from an existing genotype panel. A systematic review was conducted for each SNP in the panel to determine suitability as a PTB candidate. Those with significant associations previously reported in Caucasians were selected for replication. Candidate SNPs were already genotyped in cases and controls and clinical data were accessed from state perinatal and cerebral palsy databases. Association analysis was conducted between each SNP and PTB, and meta-analysis was conducted if there were ≥3 studies in the literature. Maternal and fetal SNPs were considered as separate candidates. results: A cohort of 170 cases and 583 controls was formed. Eight SNPs from the original panel of genotyped SNPs were selected as PTB candidates and for replication on the basis of systematic literature review results. In our cohort, fetal factor V Leiden (FVL) was significantly associated with PTB (odds ratio (OR): 2.6, 95% confidence interval (CI): 1.31-5.17), and meta-analysis confirmed this association (OR: 2.71, 95% CI: 1.15-6.4). conclusion: Replication and meta-analysis support an increased risk of PTB in Caucasians with the fetal FVL mutation.
The Journal of Obstetrics and Gynecology Research, 2022
Aim: To evaluate the roles of four selected genetic variations in fetal and maternal progesterone receptor gene (PGR) and to identify women who may have higher or lower odds for spontaneous premature birth compared to the general population. Methods: A preliminary case-control study with two groups of pregnant women (with term and premature delivery, 218 in total) and two groups of newborns (term and preterm, 218 in total) was performed. Four single nucleotide polymorphisms (SNPs) of the progesterone receptor gene (rs1042838, rs1042839, rs10895068, and rs1942836) were genotyped. Results: There was statistically significant difference between cases and controls in the distribution of newborns' allele frequency of minor C allele of the PGR SNP rs1942836 (p = 0.03, Fishers' exact test) in favor of premature birth. A statistically significant difference between the frequency of the mothers' minor T allele of rs1042838 (p = 0.005; chi-squared test) and the mothers' minor T allele of rs1042839 (p = 0.005; chi-squared test) in favor of extremely premature birth has been found. There was a statistically significant difference between the frequency of the newborns' minor C allele of rs1942836 (p = 0.03; chi-squared test) and newborns' heterozygotes CT genotype of rs1942836 (p = 0.03; Fishers' exact test) when comparing the group of term births and the group of early premature birth. Conclusion: Our study suggests that patients with selected genetic variants of the progesterone receptor gene could have greater odds for premature birth compared to term birth. Replication studies with a larger population and different ethnicity are needed in order to confirm these findings.