Increased frequency of the DI genotype of the angiotensin-I converting enzyme and association of the II genotype with insulin resistance in polycystic ovary syndrome

Koika, Vasiliki; Georgopoulos, Neoklis A.; Piouka, Athanasia; Roupas, Nikolaos D.; Karela, Anastasia; Armeni, Anastasia; Katsantoni, Eleni; Panidis, Dimitrios

doi:10.1530/eje-11-0894

Cited by 16 publications

(15 citation statements)

References 40 publications

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“…Compared to the control cohort, both the homozygous insertion genotype ( P = 0.021) and the homozygous deletion genotype ( P = 0.015) showed a moderate increase in gliomas ( Table 3 ). Such frequency alterations of the two homozygous genotypes of a glioma-associated gene were observed for the first time in the present study, although similar changes in homozygous genotypes also have been encountered in other non-cancer disorders [ 40 , 41 ]. Moreover, the decrease in heterozygous genotype frequency in gliomas compared to either controls ( P = 0.005), or non-glioma cancers ( P = 0.020), suggests a protective role being played by the heterozygous genotype in gliomas and this is a characteristic of loci that are under the influence of balancing selection [ 27 ].…”

Section: Discussionsupporting

confidence: 86%

Glioma Association and Balancing Selection of ZFPM2

et al. 2015

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ZFPM2, encoding a zinc finger protein and abundantly expressed in the brain, uterus and smooth muscles, plays important roles in cardiac and gonadal development. Abnormal expression of ZFPM2 in ovarian tumors and neuroblastoma has been reported but hitherto its genetic association with cancer and effects on gliomas have not been studied. In the present study, the hexamer insertion-deletion polymorphism rs71305152, located within a large haplotype block spanning intron 1 to intron 3 of ZFPM2, was genotyped in Chinese cohorts of glioma (n = 350), non-glioma cancer (n = 354) and healthy control (n = 463) by direct sequencing and length polymorphism in gel electrophoresis, and ZFPM2 expression in glioma tissues (n = 69) of different grades was quantified by real-time RT-PCR. Moreover, potential natural selection pressure acting on the gene was investigated. Disease-association analysis showed that the overall genotype of rs71305152 was significantly associated with gliomas (P = 0.016), and the heterozygous genotype compared to the combined homozygous genotypes was less frequent in gliomas than in controls (P = 0.005) or non-glioma cancers (P = 0.020). ZFPM2 mRNA expression was negatively correlated with the grades of gliomas (P = 0.002), with higher expression levels in the low-grade gliomas. In the astrocytoma subtype, higher ZFPM2 expression was also correlated with the rs71305152 heterozygous genotype (P = 0.028). In addition, summary statistics tests gave highly positive values, demonstrating that the gene is under the influence of balancing selection. These findings suggest that ZFPM2 is a glioma susceptibility gene, its genotype and expression showing associations with incidence and severity, respectively. Moreover, the balancing selection acting on ZFPM2 may be related to the important roles it has to play in multiple organ development or associated disease etiology.

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Section: Discussionsupporting

confidence: 86%

Glioma Association and Balancing Selection of ZFPM2

et al. 2015

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“…To the best of our knowledge, this is the first study to assess the possible role of ACE I/D polymorphisms in the aetiopathogenesis of PCOS. [16,18,26].…”

Section: Discussionmentioning

confidence: 99%

Do ACE I/D gene polymorphism serve as a predictive marker for age at onset in PCOS?

Deepika

Reddy

Rani³

et al. 2012

J Assist Reprod Genet

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Background Polycystic ovary syndrome (PCOS) is an endocrine disorder exhibiting variable age at onset of clinical features allied with complex diseases in the later life. ACE is a pleiotropic molecule associated with various pathophysiological functions. The present study was aimed to establish the frequency of ACE I/D gene polymorphism in patients and controls and to assess the influence of this polymorphism on anthropometric and various clinical features of the condition. Methods ACE I/D genotyping was carried out in 259 PCOS patients and 315 healthy ultrasound scanned women of South Indian origin.Results The distribution of DD, ID and II genotypes in patients was 39, 37 and 24 %, whereas in the controls it was 31, 51 and 18 % respectively. Significant difference was observed in the genotypic frequency distributions between the patients and controls, however the allelic frequencies did not vary between the groups (p>0.05). Quartile analysis revealed preponderance of DD genotype in the first two quartiles and a linear increase of II genotype from first to the last quartiles. Further, Multiple Logistic regression analysis revealed significant association of ACE I/D gene polymorphism with acanthosis and age at onset (AAO) of the syndrome (p<0.05). Conclusion The present study is the first report to highlight the predisposing role of DD and protective role of ID genotype towards PCOS. Patients with single or double dose of D allele may develop PCOS symptoms at an early age and also significantly associated with acanthosis, a marker of insulin resistance.

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“…I), additive (DD vs. II), dominant (DD and DI vs. II) and recessive (DD vs. DI and II) genetic model. Since Koika et al 20 suggested that the DI genotype was associated with increased risk of PCOS in Greeks, a codominance (DI vs. DD and II) genetic model was also adopted. Furthermore, subgroup analyses stratified by ethnicity were also performed.…”

Section: Discussionmentioning

confidence: 99%

Association of angiotensin-converting enzyme gene insertion/deletion polymorphism with polycystic ovary syndrome: a meta-analysis

Jia

Wang

et al. 2012

J Renin Angiotensin Aldosterone Syst

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Introduction Angiotensin converting enzyme (ACE) is a renal enzyme catalyzing the conversion of angiotensin 1 to angiotensin 2. This, results in production of the aldosterone resulting in natrium retention and potassium excretion. ACE gene has 3 polymorphic genotypes of II, DI and DD. It has been observed in several studies and meta-analyses that patients with DD genotype are more at risk of renal and cardiovascular diseases. It seems that these effects could be due to hyperactivity of ACE gene in such patients (1,2). In addition to kidneys, ovaries have renin angiotensin system (RAS). The role of this system in ovulation and reproduction is not completely understood (3). Different histopathologic and angiogenic abnormal conditions result in pregnancy complications (4). Polycystic ovary syndrome (PCOS) is one of such conditions resulting in infertility and other complications of women's reproductive system (5). Based on a meta-analysis conducted by Jalilian et al, prevalence of PCOS in Iran was 6.8%, 4.41% and 19.5% based on NIH, ultrasound and Rotterdam criteria, respectively (6). Type 2 diabetes, obesity, metabolic syndrome, hypertension and so on are considered as risk factors of PCOS (7-9). Also metformin is used for the treatment, because of insulin resistance in such patients (10). All of these evidences give us clues that hypertension related genes like ACE my play roles in pathogenesis of PCOS. Of course it is not clear whether this role is associated with renal RAS, ovarian RAS or both. On the occasion of the clues and findings above, we intend to update the only meta-analysis conducted by Jia et al in 2013 on the association of ACE gene polymorphism and risk of PCOS (11). The reason of our attempt to update this meta-analysis was that Jia et al did not find any significant relation in their random-effect model meta-analysis. Materials and Methods We searched in databases for relevant keywords in the titles of the articles (Figure 1). Finally we found 8 relevant papers based on our inclusion criteria (similar protocols including similar criteria for their PCOS and control groups). In order to perform this meta-analysis, we used comprehensive meta-analysis version 2 software (Biostat, US). The analysis was done through the P value and sample size of each study using fixed-effect model. Analyses were performed in 5 different groups of allele and genotype comparisons (Table 1). This meta-analysis Abstract Objectives: Angiotensin converting enzyme (ACE) is an important enzyme involved in the physiopathology of renal, cardiovascular and ovarian systems. One of these ACE related diseases is polycystic ovary syndrome (PCOS). Materials and Methods: We intend to update the only meta-analysis written by Jia et al in 2013 on the association of ACE gene polymorphism and risk of PCOS. The reason of our attempt to update this meta-analysis was that they found no significant relation in their meta-analysis. For this aim, we searched in databases for relevant documents. Results: We found 8 relevant papers, 6 of which h...

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Increased frequency of the DI genotype of the angiotensin-I converting enzyme and association of the II genotype with insulin resistance in polycystic ovary syndrome

Cited by 16 publications

References 40 publications

Glioma Association and Balancing Selection of ZFPM2

Glioma Association and Balancing Selection of ZFPM2

Do ACE I/D gene polymorphism serve as a predictive marker for age at onset in PCOS?

Association of angiotensin-converting enzyme gene insertion/deletion polymorphism with polycystic ovary syndrome: a meta-analysis

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