Evidence for association of the G1733A polymorphism of the androgen receptor gene with recurrent spontaneous abortions

Karvela, Maria; Stefanakis, Nikolaos; Papadopoulou, Sophia; Tsitilou, Sonia G.; Tsilivakos, Vasileios; Lamnissou, Klea

doi:10.1016/j.fertnstert.2008.04.071

Cited by 13 publications

(11 citation statements)

References 44 publications

(44 reference statements)

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“…The outcome of pregnancy relies on the success rate of various early events, such as implantation, establishment of feto-maternal circulation and maintenance of increased blood flow to the implantation site [12,13]. The development of RSA is complex and is regulated by multiple genetic pathways.…”

Section: Resultsmentioning

confidence: 99%

“…This codon resides in the N-terminal domain of the AR that harbors the major transcription activation functions [10]. Increased androgen bioactivity may result from higher circulating androgen concentrations or from increased AR transactivational activity, which is influenced by AR gene polymorphisms and can cause increased endometrial proliferative activity [12,13]. The aim of our study was to determine whether the AR G1733A polymorphism is associated with an increased risk for RSA.…”

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confidence: 99%

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StuI polymorphism on the androgen receptor gene is associated with recurrent spontaneous abortion

Jahaninejad

Ghasemi

Kalantar

et al. 2013

J Assist Reprod Genet

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Purpose This is a case-control study to determine whether G1733A polymorphism of androgen receptor gene is associated with an increased risk for recurrent spontaneous abortion (RSA). Method A total of 85 women with at least two recurrent spontaneous abortion before 20th week of gestation composed the study group. Subjects were genotyped by the polymerase chain reaction restriction fragment length polymorphism method. Results The observed frequencies of GG, GA and AA genotypes of the G1733A polymorphism were 5.89 %, 82.35 % and 11.76 %, respectively, for the patient group and 71.76 %, 23.51 % and 4.71 %, respectively, for the control group. Allele frequencies of the G1733A polymorphism among patients and controls were 0.47 and 0.84, respectively, for the dominant allele (G) (wild type) and 0.53 and 0.16, respectively, for the A allele (mutant type). Conclusions These results indicated that the androgen receptor G1733A polymorphism is strongly associated with increased risk for RSA.Keywords Recurrent spontaneous abortion . Androgen receptor . Polymorphism . RFLP PCR Recurrent spontaneous abortion (RSA) is a reproductive problem that occurs in women in reproductive age with a frequency of 1 %-3 % [20]. It is defined as two or more repeated pregnancy losses before the 20th week of gestation [14]. The risk of miscarriage is enhanced by a variety of factors including chromosomal abnormalities, uterine abnormalities, hereditary thrombophilia, endocrinologic disorders,-immunologic factors, infections, and nutritional and environmental factors [18,19]. In women with a history of recurrent miscarriage, the risk of miscarriage in a subsequent pregnancy is about 40 % to 50 %. It has a major influence on the wellbeing and psychological status of patients, therefore improved diagnosis and development of treatment strategies is essential [6,16,23]. In the past years, research interest has been focused on the association studies between different genetic polymorphisms and recurrent spontaneous abortion.Androgens are lipophilic hormones with several physiological effects in both sexes [17]. Androgen signaling in female is very important for the differentiation of human endometrial stromal cells into decidual cell; a process is called decidualization that critically controls embryo implantation and placentation [11]. The effect of androgens such as testosterone and dihydrotestosterone mediated by androgen receptor (AR) that is a nuclear receptor [3]. Androgen receptor is widely expressed in female reproductive tissue such as endometrium [1] and binds to a steroid ligand and then is transferred into the nucleus, where it regulates the transcription of androgen-responsive genes [5]. The AR gene is located on the X chromosome between q11 and q12 loci and is composed of eight exons [2] that encode a 110-kd protein that contains an N-terminal transactivation domain, Capsule Our results indicated that the androgen receptor G1733A polymorphism is strongly associated with increased risk for RSA.T. Jahaninejad (*) :

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Section: Resultsmentioning

confidence: 99%

mentioning

confidence: 99%

StuI polymorphism on the androgen receptor gene is associated with recurrent spontaneous abortion

Jahaninejad

Ghasemi

Kalantar

et al. 2013

J Assist Reprod Genet

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“…Using pairwise tagging with MAF and r 2 cutoffs of 0.05 and 1.0, respectively, six tSNPs (rs5918757, rs5919393, rs2361634, rs5918762, rs12014709, and rs5031002) were identified for the AR gene. In addition, two exonic AR polymorphisms were further selected for analysis due to previously reported associations of these polymorphisms to pregnancy-related conditions and/or due to reported functional consequences: the AR exon-1 SNP rs6152 (Glu213Glu) was selected because it was previously shown to associate with recurrent spontaneous abortions [45], and the exon-1 CAG repeat polymorphism (CAG n ) was selected because previous studies have shown that this polymorphism affects the AR-mediated transactivation [46], correlates with the concentration of androgens [47], and associates with recurrent spontaneous abortions [48]. For the IL2RG gene, no tSNPs were identified even with a MAF cutoff of 0.…”

Section: Methodsmentioning

confidence: 99%

A Potential Novel Spontaneous Preterm Birth Gene, AR, Identified by Linkage and Association Analysis of X Chromosomal Markers

et al. 2012

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Preterm birth is the major cause of neonatal mortality and morbidity. In many cases, it has severe life-long consequences for the health and neurological development of the newborn child. More than 50% of all preterm births are spontaneous, and currently there is no effective prevention. Several studies suggest that genetic factors play a role in spontaneous preterm birth (SPTB). However, its genetic background is insufficiently characterized. The aim of the present study was to perform a linkage analysis of X chromosomal markers in SPTB in large northern Finnish families with recurrent SPTBs. We found a significant linkage signal (HLOD = 3.72) on chromosome locus Xq13.1 when the studied phenotype was being born preterm. There were no significant linkage signals when the studied phenotype was giving preterm deliveries. Two functional candidate genes, those encoding the androgen receptor (AR) and the interleukin-2 receptor gamma subunit (IL2RG), located near this locus were analyzed as candidates for SPTB in subsequent case-control association analyses. Nine single-nucleotide polymorphisms (SNPs) within these genes and an AR exon-1 CAG repeat, which was previously demonstrated to be functionally significant, were analyzed in mothers with preterm delivery (n = 272) and their offspring (n = 269), and in mothers with exclusively term deliveries (n = 201) and their offspring (n = 199), all originating from northern Finland. A replication study population consisting of individuals born preterm (n = 111) and term (n = 197) from southern Finland was also analyzed. Long AR CAG repeats (≥26) were overrepresented and short repeats (≤19) underrepresented in individuals born preterm compared to those born at term. Thus, our linkage and association results emphasize the role of the fetal genome in genetic predisposition to SPTB and implicate AR as a potential novel fetal susceptibility gene for SPTB.

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“…Existen variantes asociadas con respuestas inflamatorias excesivas y autoinmunidad, sensibilidad y metabolismo de la insulina y andrógenos, trombofilia y otros, que son revisadas a continuación. Su identificación requerirá de estudios de asociación genómica en miles de individuos (68,88) .…”

Section: -Aborto Recurrente No Relacionado Con Anomalía De Cromosomasunclassified

Enfoque actual del aborto recurrente

Pacheco

Michelena

Orihuela³

2012

An Fac med

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El tema de aborto recurrente ha tenido diversos planteamientos, de acuerdo a los progresos en la genética y biología molecular y conforme se avanzó en mejores métodos clínicos de diagnóstico. En la presente revisión, hacemos un alcance sobre los actuales conocimientos sobre la etiología, diagnóstico y manejo del aborto recurrente, así como su repercusión en la pareja que sufre de subfertilidad por esta causa.

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Evidence for association of the G1733A polymorphism of the androgen receptor gene with recurrent spontaneous abortions

Cited by 13 publications

References 44 publications

StuI polymorphism on the androgen receptor gene is associated with recurrent spontaneous abortion

StuI polymorphism on the androgen receptor gene is associated with recurrent spontaneous abortion

A Potential Novel Spontaneous Preterm Birth Gene, AR, Identified by Linkage and Association Analysis of X Chromosomal Markers

Enfoque actual del aborto recurrente

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