Volume 29, Issue 11 (1-2023)
RJMS 2023, 29(11): 487-495 |
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Dindari Parizi M. Analysis of Single Nucleotide Changes rs1894116, rs2272046 and rs2252673 in Yap1, HMGA2 and INSR Genes in People with Polycystic Ovary Syndrome by Tetra ARMS-PCR Method. RJMS 2023; 29 (11) :487-495
URL: http://rjms.iums.ac.ir/article-1-8204-en.html
URL: http://rjms.iums.ac.ir/article-1-8204-en.html
Department of Cardiovascular Medicine, Shiraz University of Medical Sciences, Shiraz, Iran , MD_parizi@yahoo.com
Abstract: (316 Views)
Background & Aims: Polycystic ovary syndrome (PCOS) is a multifactorial disorder that affects women of reproductive age. This condition is diagnosed in women with hyperandrogenism, oligomenorrhea, amenorrhea, acne, hirsutism, insulin resistance, obesity, and infertility. More than 40% of female infertility is related to PCOS. Although the main cause of this disease has not yet been fully and accurately identified, according to the common features that can be seen among PCOS patients, this syndrome can be considered a set of tissue, hormonal, and genetic abnormalities that change the expression of genes, miRNAs, factors Heredity and environment play an important role in its formation. So far, more than 100 genes related to PCOS have been identified during genetic studies. Genes that are considered the main candidate for causing this disease. Also, various genetic polymorphisms have been described for PCOS, and the association of single nucleotide polymorphisms (SNP) with the occurrence and progression of PCOS has been confirmed. SNPs are single nucleotide changes (plays) in the length of the DNA of different individuals of the same species, which are seen in more than one percent of the population. SNPs are the most important type of polymorphism and can be seen anywhere in the genome; in the coding region of structural and functional genes, regulatory regions, and even in non-coding parts of DNA. With extensive investigations on the influencing genes and their polymorphisms, it has been determined that these polymorphisms play a role in PCOS. Emphasizing that polycystic ovary syndrome is a multifactorial disease, so studies on predisposing polymorphisms can give a clear view of the disease. One of the genetic loci related to PCOS is located on chromosome 11q22.1 near the YAP1 gene (Rs1894116). The association between PCOS and single nucleotide variants in the YAP1 gene has been published in several GWAS in different populations. The YAP1 protein plays a key role in the Salvador–Warts–Hippo (Hippo-Yap) signaling network that controls cellular and organismal metabolism. Does dysregulation of this pathway contribute to the pathogenesis of metabolic diseases such as type 2 diabetes, fatty liver disease, and cardiovascular disease, all of which are potential long-term consequences of PCOS. Another related disease is endometrial cancer, which is closely related to insulin resistance (one of the symptoms of PCOS). YAP1 protein is also required for the proliferation of ovarian granulosa cells. The insulin receptor or INSR, encoded by the insulin receptor gene on chromosome 19p13.3, is essential for the insulin signaling pathway. The occurrence of any polymorphism in the INSR gene can lead to a change in the function of the insulin receptor and eventually cause PCOS. Also, creating a mutation in the INSR gene can cause hyperandrogenism, hyperinsulinemia, and insulin resistance. Various recent studies in different populations show that despite the ethnic and racial diversity among the population, a strong relationship has been found between the diversity of the INSR gene and PCOS. In addition, INSR can be considered a good genetic marker for PCOS. (Rs2252673 is considered in this study). Another SNP associated with PCOS is located on chromosome 12q14.3 near the HMGA2 gene (Rs2272046). The HMGA2 gene is strongly expressed during embryonic development and in various cancers, which means that it may play a role in controlling cell proliferation. A GWAS has identified an association between IMP2 genetic variants and the risk of type 2 diabetes. Studies show that HMGA2 is related to proliferation and reproduction, making it a plausible PCOS candidate gene. So far, no study has been reported on the relationship between rs1894116, rs2272046, and rs2252673 single nucleotide changes in Yap1, HMGA2, and INSR genes in PCOS patients in Iran. This study examines the relationship between these polymorphisms in PCOS patients in Iran. Yap1, HMGA2, and INSR genes are among the most important candidate genes for polycystic ovary syndrome. This study investigated the association between three SNPs (rs1894116, rs2272046, and rs2252673) in these three genes in women with polycystic ovary syndrome.
Methods: This study was conducted on 100 women with PCOS and 100 healthy women who met the inclusion criteria and were diagnosed by a gynecologist. LH, FSH, LH to FSH ratio, AMH, estradiol, prolactin, fasting blood sugar, and testosterone were measured. Tetra ARMS-PCR method was used to investigate the relationship between genotypes of rs1894116, rs2272046, and rs2252673 polymorphisms in Yap1, HMGA2, and INSR genes. Statistical analysis was done by SPSS.
Results: Hormones and changes in their levels are very important in polycystic ovary syndrome. In examining the number of hormones in our study, as expected, it was found that the difference in the amount of LH, FSH, the ratio of LH to FSH, AMH, estradiol, prolactin, fasting blood sugar, and testosterone in PCOS subjects was significantly increased compared to healthy subjects. In other studies, similar to our results, the hormones FSH, AMH, LH and LH/FSH, testosterone, estradiol and BMI in the PCOS group increased significantly compared to healthy people. In this study, among the three SNPs investigated, rs2272046 in the HMGA2 gene and rs1894116 in YAP1 were associated with PCOS. In rs2252673 INSR, people with a dominant genotype had a direct and significant relationship with PCOS, and the C allele in a dominant state (CC genotype) has a protective role against PCOS with a chance of 0.722. In contrast to the present study, the results of a 2014 review showed that there was a significant association between rs2252673 and PCOS. In this study, the G allele was over transmitted. This means that rs2252673 is a risk marker for PCOS. Also, the results showed that carriers of the G allele show an increase in the prevalence of PCOS, which contradicts the current finding. Also, two other studies in Turkey and India showed that SNPs rs545885277 of the INSR gene on chromosome 19 did not show a significant relationship with PCOS pathogenesis. In examining the relative risk of rs2272046 in the HMGA2 gene in patients with PCOS, it was determined by logistic regression test that there was no significant difference between the genotypic frequency of healthy and diseased individuals in homozygous, recessive, dominant, and super dominant models. The average value of body mass index and the amount of hormones in sick people increased significantly compared to healthy people. People with the dominant genotype of the rs2252673 polymorphism in the INSR gene and those with the dominant and recessive genotype of the rs1894116 polymorphism in the Yap1 gene had a direct and significant relationship with PCOS. Also, none of the rs2272046 genotypes in the HMGA2 gene had any relationship with PCOS.
Conclusion: The present findings provide evidence that two polymorphisms, rs2252673 in the INSR gene and rs1894116 in the Yap1 gene, are involved in the risk of PCOS.
Methods: This study was conducted on 100 women with PCOS and 100 healthy women who met the inclusion criteria and were diagnosed by a gynecologist. LH, FSH, LH to FSH ratio, AMH, estradiol, prolactin, fasting blood sugar, and testosterone were measured. Tetra ARMS-PCR method was used to investigate the relationship between genotypes of rs1894116, rs2272046, and rs2252673 polymorphisms in Yap1, HMGA2, and INSR genes. Statistical analysis was done by SPSS.
Results: Hormones and changes in their levels are very important in polycystic ovary syndrome. In examining the number of hormones in our study, as expected, it was found that the difference in the amount of LH, FSH, the ratio of LH to FSH, AMH, estradiol, prolactin, fasting blood sugar, and testosterone in PCOS subjects was significantly increased compared to healthy subjects. In other studies, similar to our results, the hormones FSH, AMH, LH and LH/FSH, testosterone, estradiol and BMI in the PCOS group increased significantly compared to healthy people. In this study, among the three SNPs investigated, rs2272046 in the HMGA2 gene and rs1894116 in YAP1 were associated with PCOS. In rs2252673 INSR, people with a dominant genotype had a direct and significant relationship with PCOS, and the C allele in a dominant state (CC genotype) has a protective role against PCOS with a chance of 0.722. In contrast to the present study, the results of a 2014 review showed that there was a significant association between rs2252673 and PCOS. In this study, the G allele was over transmitted. This means that rs2252673 is a risk marker for PCOS. Also, the results showed that carriers of the G allele show an increase in the prevalence of PCOS, which contradicts the current finding. Also, two other studies in Turkey and India showed that SNPs rs545885277 of the INSR gene on chromosome 19 did not show a significant relationship with PCOS pathogenesis. In examining the relative risk of rs2272046 in the HMGA2 gene in patients with PCOS, it was determined by logistic regression test that there was no significant difference between the genotypic frequency of healthy and diseased individuals in homozygous, recessive, dominant, and super dominant models. The average value of body mass index and the amount of hormones in sick people increased significantly compared to healthy people. People with the dominant genotype of the rs2252673 polymorphism in the INSR gene and those with the dominant and recessive genotype of the rs1894116 polymorphism in the Yap1 gene had a direct and significant relationship with PCOS. Also, none of the rs2272046 genotypes in the HMGA2 gene had any relationship with PCOS.
Conclusion: The present findings provide evidence that two polymorphisms, rs2252673 in the INSR gene and rs1894116 in the Yap1 gene, are involved in the risk of PCOS.
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