The product of the AHSG gene is commonly referred to as fetuin in species other than the human .
The first fetal plasma protein to be described was fetuin, which was purified from fetal and newborn calf serum. Fetuin was subsequently shown to be a very abundant plasma protein in fetal cattle, sheep, pig, and
goat, and also to be present in humans and rodents.
NCBI Summary:
The protein encoded by this gene is a negatively-charged serum glycoprotein that is synthesized by hepatocytes. The encoded protein consists of two polypeptide chains, which are both cleaved from a proprotein encoded from a single mRNA. It is involved in several processes, including endocytosis, brain development, and the formation of bone tissue. Defects in this gene are a cause of susceptibility to leanness. [provided by RefSeq, Aug 2017]
General function
Extracellular binding protein
Comment
Cellular localization
Secreted
Comment
Serum Fetuin-A levels are increased and associated with insulin resistance in women with polycystic ovary syndrome. Liu S et al. (2020) Insulin resistance (IR) is a common characteristic of women with polycystic ovary syndrome (PCOS). It has been reported that circulating Fetuin-A levels were associated with IR and type 2 diabetes mellitus (T2DM). However, previous reports were inconsistent. Two hundred seven subjects were screened for PCOS according to the diagnostic guideline of the Rotterdam consensus criterion. Serum Fetuin-A levels were measured using an ELISA kit. An independent t-test or Nonparametric test was used to detect differences between PCOS and control groups. Spearman's correlation analysis was used to examine the association of the serum Fetuin-A with other parameters. Our findings showed that circulating Fetuin-A concentration ranged from 196.6 to 418.2 μg/L for most women without PCOS (95%). Women with PCOS had higher circulating Fetuin-A levels than healthy women (437.9 ± 119.3 vs. 313.8 ± 60.5 μg/L; p < 0.01). Serum Fetuin-A was positively correlated with BMI, WHR, TG, TC, LDL-C, HOMA-IR, LH, T, and DHEA-S. Multivariate regression analysis showed that WHR, TG, HOMA-IR, and DHEA-S were independent predictors of the levels of circulating Fetuin-A. Binary logistic regression revealed that serum Fetuin-A was associated with the occurrence of PCOS. In addition, our ROC curve analysis found that the cutoff values for Fetuin-A to predict PCOS and IR were 366.3 and 412.6 μg/L. Blood Fetuin-A may be a useful biomarker for screening women for PCOS and IR.//////////////////
Ovarian function
Comment
Serum Fetuin-A levels, insulin resistance and oxidative stress in women with polycystic ovary syndrome. Enli Y 2013 et al.
Abstract This study was designed to determine serum Fetuin-A levels and establish whether serum Fetuin-A level is related with insulin resistance, oxidative stress, ovarian hyperandrogenism and dyslipidemia in women with polycystic ovary syndrome (PCOS). Twenty-two patients with PCOS and twenty-one healthy control women were evaluated in this controlled clinical study. Serum Fetuin-A, lipid fractions, glucose, insulin, malondialdehyde (MDA), myeloperoxidase (MPO), glutathione (GSH), superoxide dismutase (SOD) and other hormone (gonadotropins, androgens) levels were measured. The estimate of insulin resistance was calculated by homeostasis model assessment (HOMA-R). The women with PCOS had significantly higher serum fasting glucose, insulin, luteinizing hormone (LH), MDA, Fetuin-A levels, and LH/follicle-stimulating hormone (FSH) ratio, free androgen index (FAI), HOMA-IR than healthy women. However, sex hormone-binding globulin (SHBG) and GSH levels were significantly lower in patients with PCOS compared with controls. Fetuin-A was positively correlated with insulin, HOMA-IR and FAI. Multiple regression analysis revealed that FAI was strong predictor of serum Fetuin-A level. Serum Fetuin-A level was related with insulin resistance and ovarian hyperandrogenism in women with PCOS. These results suggest that Fetuin-A may have a role in triggering the processes leading to insulin resistance and androgen excess in PCOS.
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hardening reaction that occurs in the zona pellucida to block polyspermy can be overcome in oocyte cultures in the
presence of fetal serum or the serum component fetuin. Fetuin may also prevent precocious zona hardening by inhibiting
a ZP2 proteinase released spontaneously by cortical granules during maturation of the oocyte. Poul Erik H?et al 2001 demonstrated fetuin
mRNA in the rat ovary by reverse transcriptase-polymerase chain reaction and localized it by in situ hybridization.
Fetuin mRNA was present in all granulosa cells of growing and large follicles. Immunohistochemical analysis revealed
that the fetuin protein was only present in some of the small, growing follicles. In large, healthy follicles, fetuin protein
was confined to cumulus cells and granulosa cells bordering the antrum. Fetuin was present in atretic follicles, but the
staining pattern differed from that of healthy follicles. The follicular antrum contained a substantial amount of fetuin, but
whether granulosa cells secreted it or it originated in the ovarian blood supply could not be confirmed. Thus at least a portion of the fetuin is produced by granulosa cells of growing and large follicles, suggesting that fetuin
may function in a paracrine manner to maintain the zona pellucida in a penetrable state for fertilization.
Expression regulated by
Comment
Ovarian localization
Cumulus, Granulosa, Follicular Fluid
Comment
Fetuin-A levels in lean and obese women with polycystic ovary syndrome. Kozakowski J et al. (2014) The aim of this study was to estimate serum fetuin-A levels in lean and obese women with polycystic ovary syndrome (PCOS) and to find possible relationships between fetuin-A, metabolic factors and androgens in these patients. In 25 lean (18-38 years, BMI 17.5-25.0 kg/m2) and 15 obese women (20-41 years, BMI 28.1-53.2 kg/m2) with PCOS, anthropometric indices and body composition were measured. Fasting serum fetuin-A, adiponectin, leptin, glucose, lipids, hsCRP, insulin, androgens and SHGB levels were estimated. There was no significant difference in serum fetuin-A levels between lean and obese patients: 0.54 ± 0.13 g/L and 0.60 ± 0.14 g/L, respectively. We noted a correlation between BMI and leptin levels (r = 0.88; p < 0.0001) and a nearly significant negative correlation between BMI and adiponectin levels (r = -0.53; p = 0.11) in all subjects. In lean patients, we found a correlation between fetuin-A levels and ALT activity (r = 0.44; p < 0.05). In all participants, fetuin-A correlated directly with DHEA-S levels (r = 0.44; p < 0.03). Serum fetuin-A levels were similar in lean and obese women with PCOS. We found an association between fetuin-A levels and ALT activity in lean patients and between fetuin-A levels and DHEA-S in all women. The role of fetuin-A in the mechanisms of insulin resistance, and its potential impact on androgenic hormones production in women with PCOS, need to be tested in further studies.//////////////////
Serum and follicular fluid fetuin-A in women undergoing in vitro fertilization. Bdis J 2014 et al.
Abstract Backgrounds: This case-control study was designed to assess the possible role of fetuin-A, a multifunctional protein, in reproductive processes of women undergoing in vitro fertilization (IVF). Methods: Paired serum and follicular fluid (FF) samples were obtained from 35 unselected patients who received IVF treatment. Their main clinical chartacteristics: age 35.25.4 years, BMI 22.92.8, duration of infertility 3.22.0 years, gonadotropin administered 1199.4202.3 IU, and estradiol level on day 6 of stimulation 18271342 pmol/L. In total 25 healthy women of similar age admitted for minor elective surgery served as controls for serum analysis. Fetuin-A and high-sensitivity C-reactive protein (hsCRP) were measured in serum and FF by using commercially available ELISA kits and turbidimetric immunoassay, respectively. Results: Serum fetuin-A levels of patients participating IVF are markedly elevated when compared to those of healthy women (1.300.58 g/L vs. 0.550.09 g/L, p<0.000). Fetuin-A in FF proved to be comparable to its serum levels (1.170.45 g/L) and no relationship could be detected between the respective individual values. Moreover, markers of reproductive potential (number of oocytes and embryos) appeared to be independent of serum and FF fetuin-A. hsCRP in serum and FF was not related to fetuin-A and did not influence the number of oocytes and embryos. Conclusions: Fetuin-A concentration is high in FF of patients undergoing IVF, however, it can not be used as an estimate of fertilization success.
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Serum Fetuin-A levels, insulin resistance and oxidative stress in women with polycystic ovary syndrome. Enli Y 2013 et al.
Abstract This study was designed to determine serum Fetuin-A levels and establish whether serum Fetuin-A level is related with insulin resistance, oxidative stress, ovarian hyperandrogenism and dyslipidemia in women with polycystic ovary syndrome (PCOS). Twenty-two patients with PCOS and twenty-one healthy control women were evaluated in this controlled clinical study. Serum Fetuin-A, lipid fractions, glucose, insulin, malondialdehyde (MDA), myeloperoxidase (MPO), glutathione (GSH), superoxide dismutase (SOD) and other hormone (gonadotropins, androgens) levels were measured. The estimate of insulin resistance was calculated by homeostasis model assessment (HOMA-R). The women with PCOS had significantly higher serum fasting glucose, insulin, luteinizing hormone (LH), MDA, Fetuin-A levels, and LH/follicle-stimulating hormone (FSH) ratio, free androgen index (FAI), HOMA-IR than healthy women. However, sex hormone-binding globulin (SHBG) and GSH levels were significantly lower in patients with PCOS compared with controls. Fetuin-A was positively correlated with insulin, HOMA-IR and FAI. Multiple regression analysis revealed that FAI was strong predictor of serum Fetuin-A level. Serum Fetuin-A level was related with insulin resistance and ovarian hyperandrogenism in women with PCOS. These results suggest that Fetuin-A may have a role in triggering the processes leading to insulin resistance and androgen excess in PCOS.
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Follicle stages
Secondary, Antral
Comment
The serum protein a2-Heremans-Schmid glycoprotein/fetuin-a concentration and carotid intima-media thickness in women with polycystic ovary syndrome. Abali R et al. OBJECTIVE: To investigate fetuin-A concentrations and its association with metabolic and sonographic cardiovascular markers in women with polycystic ovary syndrome (PCOS) and healthy subjects. STUDY DESIGN: Thirty-five women with PCOS and 37 healthy control women were matched for body mass index (BMI) and age. Serum fetuin-A concentrations, and reproductive and adrenal hormones were measured, and insulin resistance and carotid intima media thickness (CIMT) were evaluated in both groups. The correlations between cardiovascular risk factors, CIMT and fetuin-A concentrations were tested. RESULTS: Mean fetuin-A concentrations were significantly elevated in the PCOS group compared with control subjects (101.2ng/ml?33.55 vs. 82.5ng/ml?32.65, P=0.019). CIMT was also higher in women with PCOS than in control subjects (0.51?0.05mm vs. 0.44?0.05mm, P<0.01). Serum lipid parameters were correlated to serum fetuin-A concentrations in the PCOS group, but no correlation was found between fetuin-A and CIMT (r(PCOS)=0.244, p(PCOS)=0.158; r(control)=-0.002, p(control)=0.988). CONCLUSION: In this, the first study of fetuin-A concentrations in PCOS, the results showed that fetuin-A concentrations were increased in euglycemic patients with PCOS.
Serum Fetuin-A levels in women with polycystic ovary syndrome. Gulhan I et al. PURPOSE: The liver-derived Fetuin-A (a2-Heremans Schmid glycoprotein) is a circulating glycoprotein that may be related to insulin resistance and polycystic ovary syndrome (PCOS). We aimed to investigate the Fetuin-A levels in patients with PCOS. METHODS: A total of 88 women were included in the study. We measured the Fetuin-A levels in 44 women with PCOS and compared with 44 healthy women. RESULTS: The mean age in control group was 28.61???5.0 (18-38) and 25.5???4.1 (17-36) in PCOS group. While there was statistically significant difference in terms of age and testosterone levels, there was no difference in terms of smoking status and BMI between the groups. Accordingly, women with PCOS were older than controls [28.61???5.0 (18-38) and 25.5???4.1 (17-36), respectively, p?=?0.002]. The mean Fetuin-A level of PCOS group was 255.4???37.2 (203.1-388.9) ng/mL and the mean Fetuin-A level of control group was 253.0???43.2 (179.9-355.4) ng/mL. There was no difference between the groups with regard to Fetuin-A, before and after adjustment for age (p values 0.780 and 0.835, respectively). CONCLUSIONS: Serum Fetuin-A levels of women with PCOS did not change in comparison with the healthy controls.