Polymorphism Archives - Revista Brasileira de Ginecologia e Obstetrícia
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Revista Brasileira de Ginecologia e Obstetrícia. 2024;46:e-rbgo12
, , , , , , , , Endometriosis is a complex disease that affects 10-15% of women of reproductive age. Familial studies show that relatives of affected patients have a higher risk of developing the disease, implicating a genetic role for this disorder. Little is known about the impact of germline genomic copy number variant (CNV) polymorphisms on the heredity of the disease. In this study, we describe a rare CNV identified in two sisters with familial endometriosis, which contain genes that may increase the susceptibility and progression of this disease. We investigated the presence of CNVs from the endometrium and blood of the sisters with endometriosis and normal endometrium of five women as controls without the disease using array-CGH through the Agilent 2x400K platform. We excluded common CNVs that were present in the database of genomic variation. We identified, in both sisters, a rare CNV gain affecting 113kb at band 3q12.2 involving two candidate genes: ADGRG7 and TFG. The CNV gain was validated by qPCR. ADGRG7 is located at 3q12.2 and encodes a G protein-coupled receptor influencing the NF-kappaβ pathway. TFG participates in chromosomal translocations associated with hematologic tumor and soft tissue sarcomas, and is also involved in the NF-kappa B pathway. The CNV gain in this family provides a new candidate genetic marker for future familial endometriosis studies. Additional longitudinal studies of affected families must confirm any associations between this rare CNV gain and genes involved in the NF-kappaβ pathway in predisposition to endometriosis.
Summary
Revista Brasileira de Ginecologia e Obstetrícia. 2024;46:e-rbgo12
, , , , , , , , Endometriosis is a complex disease that affects 10-15% of women of reproductive age. Familial studies show that relatives of affected patients have a higher risk of developing the disease, implicating a genetic role for this disorder. Little is known about the impact of germline genomic copy number variant (CNV) polymorphisms on the heredity of the disease. In this study, we describe a rare CNV identified in two sisters with familial endometriosis, which contain genes that may increase the susceptibility and progression of this disease. We investigated the presence of CNVs from the endometrium and blood of the sisters with endometriosis and normal endometrium of five women as controls without the disease using array-CGH through the Agilent 2x400K platform. We excluded common CNVs that were present in the database of genomic variation. We identified, in both sisters, a rare CNV gain affecting 113kb at band 3q12.2 involving two candidate genes: ADGRG7 and TFG. The CNV gain was validated by qPCR. ADGRG7 is located at 3q12.2 and encodes a G protein-coupled receptor influencing the NF-kappaβ pathway. TFG participates in chromosomal translocations associated with hematologic tumor and soft tissue sarcomas, and is also involved in the NF-kappa B pathway. The CNV gain in this family provides a new candidate genetic marker for future familial endometriosis studies. Additional longitudinal studies of affected families must confirm any associations between this rare CNV gain and genes involved in the NF-kappaβ pathway in predisposition to endometriosis.
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Revista Brasileira de Ginecologia e Obstetrícia. 2020;42(8):460-467
, , , , , , , , We examined the interaction of polymorphisms in the genes heme oxygenase- 1 (HMOX1) and nitric oxide synthase (NOS3) in patients with preeclampsia (PE) as well as the responsiveness to methyldopa and to total antihypertensive therapy.
The genes HMOX1 (rs2071746, A/T) and NOS3 (rs1799983, G/T) were genotyped using TaqMan allele discrimination assays (Applied Biosystems, Foster City, CA, USA ), and the levels of enzyme heme oxygenase-1 (HO-1) were measured using enzyme-linked immunosorbent assay (ELISA).
We found interactions between genotypes of the HMOX-1 and NOS3 genes and responsiveness tomethyldopa and that PE genotyped as AT presents lower levels of protein HO-1 compared with AA.
We found interactions between the HMOX-1 and NOS3 genes and responsiveness to methyldopa and that the HMOX1 polymorphism affects the levels of enzyme HO-1 in responsiveness to methyldopa and to total antihypertensive therapy. These data suggest impact of the combination of these two polymorphisms on antihypertensive responsiveness in PE.
Summary
Revista Brasileira de Ginecologia e Obstetrícia. 2020;42(8):460-467
, , , , , , , , We examined the interaction of polymorphisms in the genes heme oxygenase- 1 (HMOX1) and nitric oxide synthase (NOS3) in patients with preeclampsia (PE) as well as the responsiveness to methyldopa and to total antihypertensive therapy.
The genes HMOX1 (rs2071746, A/T) and NOS3 (rs1799983, G/T) were genotyped using TaqMan allele discrimination assays (Applied Biosystems, Foster City, CA, USA ), and the levels of enzyme heme oxygenase-1 (HO-1) were measured using enzyme-linked immunosorbent assay (ELISA).
We found interactions between genotypes of the HMOX-1 and NOS3 genes and responsiveness tomethyldopa and that PE genotyped as AT presents lower levels of protein HO-1 compared with AA.
We found interactions between the HMOX-1 and NOS3 genes and responsiveness to methyldopa and that the HMOX1 polymorphism affects the levels of enzyme HO-1 in responsiveness to methyldopa and to total antihypertensive therapy. These data suggest impact of the combination of these two polymorphisms on antihypertensive responsiveness in PE.
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Revista Brasileira de Ginecologia e Obstetrícia. 2020;42(3):146-151
, , , , , , , , To investigate the association between genetic polymorphisms in candidate genes or candidate regions and the development of endometriosis in Brazilian women.
A total of 30 women between 25 and 64 years old with a diagnosis of endometriosis participated in the present study, as well as 30 matched control women from the same age group, asymptomatic and without family history of the disease. The patients genotypic and allelic frequencies of polymorphisms in the GREB1 gene (rs13394619) and in the intergenic region at position 7p15.2 (rs12700667) were analyzed and compared.
There was no significant difference in the frequency of genotypes for the A > G polymorphism (rs13394619) in the GREB1 gene between the two groups. However, the distribution frequencies of the genotypes for the A > G polymorphism (rs12700667) in an intergenic region on chromosome 7 were different for control patients and for patients with endometriosis, with higher frequency of the AG genotype compared to the GG between patients with the disease (odds ratio [OR] = 3.49; confidence interval [CI] = 1.47–8.26).
The present study suggests that the polymorphism in the intergenic region of chromosome 7 is associated with the risk of developing endometriosis in a population of Brazilian women from Juiz de Fora.
Summary
Revista Brasileira de Ginecologia e Obstetrícia. 2020;42(3):146-151
, , , , , , , , To investigate the association between genetic polymorphisms in candidate genes or candidate regions and the development of endometriosis in Brazilian women.
A total of 30 women between 25 and 64 years old with a diagnosis of endometriosis participated in the present study, as well as 30 matched control women from the same age group, asymptomatic and without family history of the disease. The patients genotypic and allelic frequencies of polymorphisms in the GREB1 gene (rs13394619) and in the intergenic region at position 7p15.2 (rs12700667) were analyzed and compared.
There was no significant difference in the frequency of genotypes for the A > G polymorphism (rs13394619) in the GREB1 gene between the two groups. However, the distribution frequencies of the genotypes for the A > G polymorphism (rs12700667) in an intergenic region on chromosome 7 were different for control patients and for patients with endometriosis, with higher frequency of the AG genotype compared to the GG between patients with the disease (odds ratio [OR] = 3.49; confidence interval [CI] = 1.47–8.26).
The present study suggests that the polymorphism in the intergenic region of chromosome 7 is associated with the risk of developing endometriosis in a population of Brazilian women from Juiz de Fora.
, Summary
Revista Brasileira de Ginecologia e Obstetrícia. 2019;41(3):164-169
, To evaluate the C-1562T matrix metalloproteinase 9 (MMP9) gene polymorphisms as risk factors related to the occurrence of pelvic organ prolapse (POP) and to identifytheclinicalvariablesassociatedwith theoccurrenceof thedisease.Epidemiological studies of risk factors for POP do not explain why nulliparous women with no known risk factors also develop POP. Therefore, genetic factors may be involved.
Cohort study with 86 women with symptomatic POP (cases), and 158 women withoutapriororcurrentdiagnosisof thisdisorder(controls).Thegroupswereanalyzedfor the presence of MMP9 gene polymorphisms. Genotyping was performed using polymerase chainreaction(PCR)with DNA obtained froma peripheral venouspuncture ofboth groups.
There were no differences between the cases and controls even when we grouped the mutant homozygous and heterozygous genotypes. The analysis of patients with a complete absence of POP versus patients with total POP also showed no statistically significant differences. Ageand home birth were found to be independent risk factors for POP.
There were no statistically significant differences in the C-1562T MMP9 polymorphisms between the cases and controls in Brazilian women.
Summary
Revista Brasileira de Ginecologia e Obstetrícia. 2019;41(3):164-169
, To evaluate the C-1562T matrix metalloproteinase 9 (MMP9) gene polymorphisms as risk factors related to the occurrence of pelvic organ prolapse (POP) and to identifytheclinicalvariablesassociatedwith theoccurrenceof thedisease.Epidemiological studies of risk factors for POP do not explain why nulliparous women with no known risk factors also develop POP. Therefore, genetic factors may be involved.
Cohort study with 86 women with symptomatic POP (cases), and 158 women withoutapriororcurrentdiagnosisof thisdisorder(controls).Thegroupswereanalyzedfor the presence of MMP9 gene polymorphisms. Genotyping was performed using polymerase chainreaction(PCR)with DNA obtained froma peripheral venouspuncture ofboth groups.
There were no differences between the cases and controls even when we grouped the mutant homozygous and heterozygous genotypes. The analysis of patients with a complete absence of POP versus patients with total POP also showed no statistically significant differences. Ageand home birth were found to be independent risk factors for POP.
There were no statistically significant differences in the C-1562T MMP9 polymorphisms between the cases and controls in Brazilian women.
Summary
Revista Brasileira de Ginecologia e Obstetrícia. 2019;41(1):31-36
To evaluate the rs42524 polymorphism of the procollagen type I alpha (α) 2 (COL1A2) gene as a factor related to the development of pelvic organ prolapse (POP) in Brazilian women.
The present study involved 112 women with POP stages III and IV (case group) and 180 women with POP stages zero and I (control group). Other clinical data were obtained by interviewing the patients about their medical history, and blood was also collected from the volunteers for the extraction of genomic DNA. The promoter region of the COL1A2 gene containing the rs42524 polymorphism was amplified, and the discrimination between the G and C variants was performed by digestion of the polymerase chain reaction (PCR) products with the MspA1I enzyme followed by agarose gel electrophoresis analysis.
A total of 292 women were analyzed. In the case group, 71 had the G/G genotype, 33 had the G/C genotype, and 7 had the C/C genotype. In turn, the ratio in the control group was 117 G/G, 51 G/C, and 11 C/C. There were no significant differences between the groups.
Our data did not show an association between the COL1A2 polymorphism and the occurrence of POP.
Summary
Revista Brasileira de Ginecologia e Obstetrícia. 2019;41(1):31-36
To evaluate the rs42524 polymorphism of the procollagen type I alpha (α) 2 (COL1A2) gene as a factor related to the development of pelvic organ prolapse (POP) in Brazilian women.
The present study involved 112 women with POP stages III and IV (case group) and 180 women with POP stages zero and I (control group). Other clinical data were obtained by interviewing the patients about their medical history, and blood was also collected from the volunteers for the extraction of genomic DNA. The promoter region of the COL1A2 gene containing the rs42524 polymorphism was amplified, and the discrimination between the G and C variants was performed by digestion of the polymerase chain reaction (PCR) products with the MspA1I enzyme followed by agarose gel electrophoresis analysis.
A total of 292 women were analyzed. In the case group, 71 had the G/G genotype, 33 had the G/C genotype, and 7 had the C/C genotype. In turn, the ratio in the control group was 117 G/G, 51 G/C, and 11 C/C. There were no significant differences between the groups.
Our data did not show an association between the COL1A2 polymorphism and the occurrence of POP.
Summary
Revista Brasileira de Ginecologia e Obstetrícia. 2018;40(11):699-704
Epidemiological studies have shown evidence of the effect of sex hormones in the pathogenesis of breast cancer, and have suggested a relationship of the disease with variations in genes involved in estrogen synthesis and/or metabolism. The aim of the present study was to evaluate the association between the CYP3A4*1B gene polymorphism (rs2740574) and the risk of developing breast cancer.
In the present case-control study, the frequency of the CYP3A4*1B gene polymorphism was determined in 148 women with breast cancer and in 245 women without the disease. The DNA of the participants was extracted from plasma samples, and the gene was amplified by polymerase chain reaction. The presence of the polymorphism was determined using restriction enzymes.
After adjusting for confounding variables, we have found that the polymorphism was not associated with the occurrence of breast cancer (odds ratio = 1.151; 95% confidence interval: 0.714–1.856; p= 0.564). We have also found no association with the presence of hormone receptors, with human epidermal growth factor receptor 2 (HER2) overexpression, or with the rate of tumor cell proliferation.
We have not observed a relationship between the CYP3A4*1B gene polymorphism and the occurrence of breast cancer.
Summary
Revista Brasileira de Ginecologia e Obstetrícia. 2018;40(11):699-704
Epidemiological studies have shown evidence of the effect of sex hormones in the pathogenesis of breast cancer, and have suggested a relationship of the disease with variations in genes involved in estrogen synthesis and/or metabolism. The aim of the present study was to evaluate the association between the CYP3A4*1B gene polymorphism (rs2740574) and the risk of developing breast cancer.
In the present case-control study, the frequency of the CYP3A4*1B gene polymorphism was determined in 148 women with breast cancer and in 245 women without the disease. The DNA of the participants was extracted from plasma samples, and the gene was amplified by polymerase chain reaction. The presence of the polymorphism was determined using restriction enzymes.
After adjusting for confounding variables, we have found that the polymorphism was not associated with the occurrence of breast cancer (odds ratio = 1.151; 95% confidence interval: 0.714–1.856; p= 0.564). We have also found no association with the presence of hormone receptors, with human epidermal growth factor receptor 2 (HER2) overexpression, or with the rate of tumor cell proliferation.
We have not observed a relationship between the CYP3A4*1B gene polymorphism and the occurrence of breast cancer.
Summary
Revista Brasileira de Ginecologia e Obstetrícia. 2018;40(10):631-641
Previous studies investigating the association between angiotensin-converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism and recurrent pregnancy loss (RPL) risk has provided inconsistent results. The aim of our study was to assess the association between the ACE I/D polymorphism and risk of RPL.
All studies published up to January 30, 2018 on the association of ACE I/D polymorphism with RPL were identified by searching the PubMed, Web of Knowledge, and Google scholar databases.
A total of 26 case-control studies with 3,140 RPL cases and 3,370 controls were included in themeta-analysis. Overall, there was a significant association between ACE I/D polymorphism and RPL risk under the allele model (I versus D: odds ratio [OR] = 0.538, 95% confidence interval [CI] = 0.451-0.643, p 0.001), the homozygote model (II versus DD: OR = 0.766, 95% CI = 0.598-0.981, p = 0.035) and the recessive model (II versus ID + DD: OR = 0.809, 95% CI = 0.658-0.994, p = 0.044). Subgroup analysis by ethnicity showed that there was a significant association between ACE I/D polymorphism and increased risk of RPL in Caucasian and West-Asian populations, but not in East-Asians. When stratified by number of recurrent miscarriages (RMs), a significant association between ACE I/D polymorphism and increased risk of RPL was detected in the group of studies with ≥ 2 RMs, but not in studies with ≥ 3 RMs.
Themeta-analysis suggests that ACE I/D polymorphism is associated with increased risk of RPL. The ACE I/D polymorphism may be a risk factor for RPL in Caucasian and West-Asian populations, but not in East-Asians.
Summary
Revista Brasileira de Ginecologia e Obstetrícia. 2018;40(10):631-641
Previous studies investigating the association between angiotensin-converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism and recurrent pregnancy loss (RPL) risk has provided inconsistent results. The aim of our study was to assess the association between the ACE I/D polymorphism and risk of RPL.
All studies published up to January 30, 2018 on the association of ACE I/D polymorphism with RPL were identified by searching the PubMed, Web of Knowledge, and Google scholar databases.
A total of 26 case-control studies with 3,140 RPL cases and 3,370 controls were included in themeta-analysis. Overall, there was a significant association between ACE I/D polymorphism and RPL risk under the allele model (I versus D: odds ratio [OR] = 0.538, 95% confidence interval [CI] = 0.451-0.643, p 0.001), the homozygote model (II versus DD: OR = 0.766, 95% CI = 0.598-0.981, p = 0.035) and the recessive model (II versus ID + DD: OR = 0.809, 95% CI = 0.658-0.994, p = 0.044). Subgroup analysis by ethnicity showed that there was a significant association between ACE I/D polymorphism and increased risk of RPL in Caucasian and West-Asian populations, but not in East-Asians. When stratified by number of recurrent miscarriages (RMs), a significant association between ACE I/D polymorphism and increased risk of RPL was detected in the group of studies with ≥ 2 RMs, but not in studies with ≥ 3 RMs.
Themeta-analysis suggests that ACE I/D polymorphism is associated with increased risk of RPL. The ACE I/D polymorphism may be a risk factor for RPL in Caucasian and West-Asian populations, but not in East-Asians.
Summary
Revista Brasileira de Ginecologia e Obstetrícia. 2011;33(5):246-251
DOI 10.1590/S0100-72032011000500007
PURPOSE: to evaluate the prevalence of cytogenetic alterations and chromosomic polymorphism in couples with a subfertility phenotype in a Brazilian population. METHODS: karyotype analysis through G and C banding of 1,236 individuals who presented the subfertility phenotype, from two different centers (public and private) were included in the study. These patients were classified in two sub-groups: one with two or more gestational consecutive losses or not and the o with, at least, one gestacional loss or absence of conception. Karyotype results were evaluated in different groups and frequencies were calculated. Statistical analyses were carried out through Fisher's exact test and Odds Ratio analysis. RESULTS: approximately 25% of the cases presented abnormal karyotype results, including numerical and structural alterations and also polymorphic variants. In both centers, the prevalence of polymorphic variants was 8.9 and 3.8%, respectively. CONCLUSIONS: there was no significant difference between the prevalence of polymorphic variants and other abnormalities in individuals with or without previous history of reproductive loss. The results of the present study reinforce the need of adequate disclosure of complete cytogenetic information in the karyotype results, with specific attention in relation to the polymorphic variants.
Summary
Revista Brasileira de Ginecologia e Obstetrícia. 2011;33(5):246-251
DOI 10.1590/S0100-72032011000500007
PURPOSE: to evaluate the prevalence of cytogenetic alterations and chromosomic polymorphism in couples with a subfertility phenotype in a Brazilian population. METHODS: karyotype analysis through G and C banding of 1,236 individuals who presented the subfertility phenotype, from two different centers (public and private) were included in the study. These patients were classified in two sub-groups: one with two or more gestational consecutive losses or not and the o with, at least, one gestacional loss or absence of conception. Karyotype results were evaluated in different groups and frequencies were calculated. Statistical analyses were carried out through Fisher's exact test and Odds Ratio analysis. RESULTS: approximately 25% of the cases presented abnormal karyotype results, including numerical and structural alterations and also polymorphic variants. In both centers, the prevalence of polymorphic variants was 8.9 and 3.8%, respectively. CONCLUSIONS: there was no significant difference between the prevalence of polymorphic variants and other abnormalities in individuals with or without previous history of reproductive loss. The results of the present study reinforce the need of adequate disclosure of complete cytogenetic information in the karyotype results, with specific attention in relation to the polymorphic variants.