Species: mouse
Mutation name: None
type: null mutation
fertility: fertile
Comment: Krege et al. (1995) investigated the role of the ACE gene in blood pressure control and reproduction using mice generated to carry an insertional mutation that was designed to inactivate both forms of ACE. All homozygous female mutants were found to be fertile, but the fertility of homozygous male mutants was greatly reduced.

Species: human
Mutation name: None
type: naturally occurring
fertility: subfertile
Comment: Angiotensin-converting enzyme gene polymorphism and risk of insulin resistance in PCOS. Celik O et al. The aim of this study was to establish the frequency of angiotensin-converting enzyme (ACE) insertion (I) or deletion (D) gene polymorphism in women with polycystic ovary syndrome (PCOS) and to examine the association of this polymorphism with insulin resistance. A total of 32 women with PCOS and 31 healthy, age- and body mass index-matched controls were studied. Serum lipids, fasting glucose, insulin and other hormones concentrations were measured. Homeostasis model assessment was used to estimate insulin resistance (HOMA-IR). DNA was extracted from peripheral blood leukocytes and genotyping of ACE I/D polymorphism was carried out by polymerase chain reaction. ACE genotypes were distributed as follows: DD was present in 16 (50%), ID in 12 (37.5%) and II in four (12.5%) PCOS patients, and DD in seven (22.6%), ID in 20 (64.5%) and II in four (12.9%) of healthy subjects. The frequency of D and I alleles were found in 69% and 31% of the PCOS group and 55% and 45% in the control group, respectively. There were no significant differences regarding the genotypic distribution and allelic frequency between the groups. However the ACE DD genotype was significantly associated with serum insulin concentrations and HOMA-IR measurement (both P=0.005). ACE DD genotype is associated with an increased insulin resistance in women with PCOS.

Species: human
Mutation name: None
type: naturally occurring
fertility: subfertile
Comment: Angiotensin converting enzyme gene insertion/deletion polymorphism in patients with polycystic ovary syndrome. Karabulut A et al. Objective. The aim of this study is to investigate the relevance of polymorphism in angiotensin converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism to the pathophysiology of polycystic ovary syndrome (PCOS). Subjects and methods. Thirty patients with PCOS by Rotterdam consensus criteria and 33 control subjects were prospectively investigated. ACE gene amplification of DNA was performed by polymerase chain reaction. Homeostatic model assessment (HOMA-IR) was applied. Results. Compared to controls, ACE gene DD genotype and D allele were observed more frequently in PCOS (63% vs. 46% for DD genotype and 75% vs. 67% for D allele) (p > 0.05). Body mass index, fasting glucose and insulin levels, HOMA-IR index and total testosterone levels were higher in PCOS group (p < 0.05). The frequencies of D and I alleles were 45 (75%) and 15 (25%) for PCOS group and 44 (67%) and 22 (33%) for control group (p > 0.05). No significant differences were observed in the genotype and allele distributions between cases and control groups. HOMA-IR index was significantly higher in patients with PCOS with DD genotype than those with II genotype (p < 0.05). Conclusion. The ACE gene polymorphism was not associated with PCOS. However, the presence of D allele was associated with higher rate of insulin resistance in patients with PCOS.

Species: human
Mutation name: None
type: naturally occurring
fertility: subfertile
Comment: Association of angiotensin converting enzyme (ACE) gene I/D polymorphism and polycystic ovary syndrome (PCOS). Bayram B et al. This study was conducted in Turkish patients with polycystic ovary syndrome to determine the frequency of I/D polymorphism genotypes of angiotensin converting enzyme gene, and to examine the role of this polymorphism in polycystic ovary syndrome development. Genomic DNA obtained from 200 persons (100 patients with polycystic ovary syndrome and 100 healthy controls) was used in the study. DNA was multiplied by polymerase chain reaction using I and D allele-specific primers. Polymerase chain reaction products were assessed with a charge coupled device (CCD) camera by being exposed to 2% agarose gel electrophoresis. There was statistically significant difference between the groups with respect to genotype distribution (p<0.001). The D allele frequency was indicated as 68% and I allele was as 32% in the patients, whereas it was 51.5-48.5% respectively in the control group. As a result of our study we may assert that angiotensin converting enzyme gene I/D polymorphism DD genotype should be considered as a genetic marker in polycystic ovary syndrome development in this Turkish study population.

Species: human
Mutation name: None
type: naturally occurring
fertility: subfertile
Comment: Increased frequency of the DI genotype of the Angiotensin-I Converting Enzyme (ACE) and association of the II genotype with Insulin Resistance in Polycystic Ovary Syndrome. Koika V et al. Objective: The polycystic ovary syndrome (PCOS) is a common and complex disease with unclear pattern of inheritance, characterized by an androgen excess, while hyperinsulinemia and insulin resistance (IR) are common features of the syndrome. The Angiotensin-I Converting Enzyme (ACE) I/D gene polymorphism was proved to be involved in many pathophysiological conditions, including hypertension, and IR.Design: The purpose of this study was to evaluate the involvement of the ACE gene polymorphism in the pathogenesis of PCOS.Methods: In a case control association study involving 801 PCOS women and 266 healthy controls, hormonal determinations and ACE polymorphism genotyping were performed. The PCOS women were classified into 3 groups: Group A presented biochemical hyperandrogenism, combined with anovulation and polycystic ovarian morphology, Group B clinical hyperandrogenism combined with anovulation and polycystic ovarian morphology and Group C chronic anovulation and polycystic ovarian morphology.Results: A significant increase of the frequency of the DI genotype of ACE polymorphism was detected in PCOS women as a whole (p = 0.035), in PCOS Group A (p = 0.039) and Group B (p=0.010), while there was no difference for Group C (p=0.939). Significant difference was also observed in hyperandrogenic PCOS women as a whole (Group A+B) (p=0.017). The II genotype, was positively correlated with HOMA-IR and Quick indices, and with fasting insulin and glucose/insulin ratio in these groups.Conclusions: The association study of the ACE I/D polymorphism in PCOS women demonstrates an increase in the DI genotype incidence, and an association of the II genotype with IR. Association of angiotensin-converting enzyme gene insertion/deletion polymorphism with polycystic ovary syndrome: a meta-analysis. Jia H et al. INTRODUCTION: Epidemiological studies investigating the association of angiotensin-converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism with polycystic ovary syndrome (PCOS) produced inconsistent results. To derive a more precise estimation of the relationship between I/D polymorphism and PCOS, we conducted the current meta-analysis. MATERIALS AND METHODS: PubMed, Web of Science and CNKI were searched for eligible publications up to 1 February 2012. The association was evaluated under different genetic models. RESULTS: Six studies with 1451 cases and 773 controls were finally included in our meta-analysis. The results showed that no significant association between I/D polymorphism and PCOS was observed in the overall population. However, in subgroup analyses stratified by ethnicity, significant association was observed in Caucasians (OR = 1.48, 95% CI, 1.00-2.19 for D vs. I; OR = 1.61, 95% CI, 1.14-2.27 for DD vs. II; OR = 1.43, 95% CI, 1.04-1.97 for DD and DI vs. II), but not in Asians. CONCLUSIONS: Our meta-analysis suggested that the ACE I/D polymorphism was associated with increased risk of PCOS in Caucasians, but not in Asians. However, considering that the conclusions were based on a relatively small sample size, larger studies involving various ethnic populations should be warranted in future studies to validate our findings.

Species: human
Mutation name:
type: naturally occurring
fertility: subfertile
Comment: Association between the angiotensin converting enzyme gene insertion/deletion polymorphism and metabolic disturbances in women with polycystic ovary syndrome. Ożegowska K et al. (2016) Polycystic ovary syndrome (PCOS) is a common endocrine disorder in women of reproductive age. A number of PCOS complications may be associated with the elevated level of angiotensin II and low bradykinin concentrations. The aim of the present study was to investigate the frequencies of angiotensin converting enzyme (ACE) gene insertion/deletion (I/D) polymorphisms in women with PCOS and to determine the association between ACE genetic variants and the risk of metabolic and cardiovascular complications in such women. A total of 138 PCOS patients and 110 healthy volunteers were enrolled. Cardiovascular risk was estimated according to the criteria of the American Heart Association and Androgen Excess and PCOS Society. The median average age was 28.5 (26.0‑31.0) and 27.0 (24.0‑30.0) years in the control and PCOS groups, respectively (P=0.004). Anthropometric parameters, including body mass index and waist circumference were significantly higher in the PCOS patients. In the PCOS group, 97 (57.4%) of the subjects were metabolically unhealthy, whereas, in the control group 51 (46.4%) subjects were (P=0.07). The II, ID, and DD genotypes frequencies were 29.1, 44.5, and 26.4% in the controls and 5.0, 37.7, and 57.3% in the PCOS patients. The cardioprotective I allele was observed significantly less frequently in the women with PCOS compared with the controls [odds ratio (OR), 3.27; P=0.0001]. The DD genotype, which is known to increase cardiovascular risk, was more frequently observed in PCOS patients (OR, 3.87; P=0.0003), whereas the cardioprotective II genotype occurred in this group less frequently (OR, 0.4; P=0.06). The results of the present study demonstrated a statistically significant association between the ACE I/D polymorphism and the presence and intensity of metabolic disturbances in women with PCOS.//////////////////