Hereditary Persistence of Alpha-Fetoprotein Is Associated with the —119G&gt;A Polymorphism in AFP Gene

Deshpande, Neha; Chavan, Radhika; Bale, Govardhan; Avanthi, Urmila Steffie; Aslam, Mohsin; Ramchandani, Mohan; Reddy, D. Nageshwar; Vishnubhotla, Ravikanth

doi:10.14309/crj.2017.33

Cited by 4 publications

(6 citation statements)

References 9 publications

(14 reference statements)

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“…The first clinical case of HPAFP was described in 1983 by Ferguson et al. in a Scottish family, and after this report, it has been observed in more than 20 families worldwide 28–30 …”

Section: Discussionmentioning

confidence: 93%

“…Scottish family, and after this report, it has been observed in more than 20 families worldwide. [28][29][30] To our knowledge, our study is the first to report high level of serum AFP in a homogeneous large cohort of non-Finnish White European men presenting for primary couple's infertility at a single academic institution and without an history of other diseases associated with potential AFP rise. Of clinical relevance, high AFP emerged to be independently associated with higher frequency of impaired sperm count after accounting for several known risk factors.…”

Section: Discussionmentioning

confidence: 99%

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High serum alpha‐fetoprotein levels in primary infertile men

et al. 2022

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Background Alfa‐fetoprotein (AFP) is a serum glycoprotein highly produced during fetal development. While AFP synthesis drops dramatically after birth, AFP production only persists or returns under specific pathological condition. Objective We sought to investigate the rate of and the potential meaning of high AFP serum levels in men seeking first medical attention for couple's primary infertility. Materials and methods Socio‐demographic and clinical data from 1803 non‐Finnish, White‐European primary infertile men were retrospectively analysed. AFP was routinely measured in each patient (high AFP was defined as >7 ng/ml). Men with history of liver diseases, testicular cancer, or other known causes of increased AFP levels were excluded from the final analysis. Semen analyses were based on the 2010 World Health Organization reference criteria. Descriptive statistics and logistic regression models tested the association between serum AFP and clinical variables. Possible nonlinear relationships were graphically explored with locally estimated scatterplot smoothing method. Results Overall, high serum AFP level was found in 29 (1.7%) patients. Normal versus high AFP levels patients were comparable in terms of body mass index (BMI), Charlson Comorbidity Index, waist circumference, smoking habits, history of cryptorchidism, testicular volume, and serum hormones (i.e., follicle‐stimulating hormone, luteinizing hormone, and total testosterone). Conversely, men with higher AFP levels were older (p = 0.02), had lower sperm concentration (p = 0.003), and were more frequently oligozoospermic and azoospermic (all p ≤ 0.03). At multivariate analysis, high AFP levels were independently associated with oligozoospermia (OR 3.79; p = 0.033) and azoospermia (OR 3.29; p = 0.006). Likewise, if AFP levels increase, patients were found to be older, with higher BMI and to have more comorbidities (all p < 0.05). Discussion Unexplained high AFP levels account for almost 2% of cases in primary infertile patients without a previous history of associated disorders. Higher serum AFP levels are linked with aberrant sperm counts, older age, obesity, and a greater amount of comorbid conditions. Conclusion Despite the need for additional validation, these data suggest that serum AFP measurement might have a multifaceted role over the diagnostic work‐up of males presenting for couple's infertility.

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“…The first clinical case of HPAFP was described in 1983 by Ferguson et al. in a Scottish family, and after this report, it has been observed in more than 20 families worldwide 28–30 …”

Section: Discussionmentioning

confidence: 93%

Section: Discussionmentioning

confidence: 99%

High serum alpha‐fetoprotein levels in primary infertile men

et al. 2022

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“…Besides, the overall survival rate was significantly higher in patients with low ACLY expression than that with high ACLY expression. AFP is a glycoprotein, which is mainly synthesized in the foetal liver and reaches its peak in the third month of gestation, and then gradually decline 32,33 . However, HCC resumes the function of producing AFP when liver cells become cancerous, which is a good indicator of HCC screening and postoperative follow‐up 34 .…”

Section: Discussionmentioning

confidence: 99%

“…AFP is a glycoprotein, which is mainly synthesized in the foetal liver and reaches its peak in the third month of gestation, and then gradually decline. 32,33 However, HCC resumes the function of producing AFP when liver cells become cancerous, which is a good indicator of HCC screening and postoperative follow-up. 34 In our study, AFP and ACLY expression abundance were both independent risk factors affecting the overall survival of patients, but AFP was not associated with ACLY expression, which requires further study in the future.…”

Section: Discussionmentioning

confidence: 99%

ATP citrate lyase inhibitor triggers endoplasmic reticulum stress to induce hepatocellular carcinoma cell apoptosis via p‐eIF2α/ATF4/CHOP axis

Zheng

Zhou

Zhao

et al. 2021

J Cellular Molecular Medi

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ATP citrate lyase (ACLY), a key enzyme in the metabolic reprogramming of many cancers, is widely expressed in various mammalian tissues. This study aimed to evaluate the effects and mechanisms of ACLY and its inhibitor BMS‐303141 on hepatocellular carcinoma (HCC). In this study, ACLY was highly expressed in HCC tissues, especially in HepG2 and Huh7 cells, but was down‐regulated in Hep3B and HCC‐LM3 cells. Besides, ACLY knockdown inhibited HepG2 proliferation and clone formation, while opposite result was noticed in HCC‐LM3 cells with ACLY overexpression. Moreover, ACLY knockdown impeded the migration and invasion abilities of HepG2 cells. Similarly, BMS‐303141 suppressed HepG2 and Huh‐7 cell proliferation. The p‐eIF2α, ATF4, CHOP p‐IRE1α, sXBP1 and p‐PERK were activated in HepG2 cells stimulated by BMS‐303141. In cells where ER stress was induced, ATF4 was involved in BMS‐303141‐mediated cell death procession, and ATF4 knockdown reduced HCC cell apoptosis stimulated by BMS‐303141. In a mouse xenograft model, combined treatment with BMS‐303141 and sorafenib reduced HepG2 tumour volume and weight. In addition, ACLY expression was associated with HCC metastasis and tumour‐node‐metastases staging. Survival analysis and Cox proportional hazards regression model showed that overall survival was lower in HCC patients with high ACLY expression; AFP level, TNM staging, tumour size and ACLY expression level were independent risk factors affecting their overall survival. In conclusion, ACLY might represent a promising target in which BMS‐303141 could induce ER stress and activate p‐eIF2α/ATF4/CHOP axis to promote apoptosis of HCC cells, and synergized with sorafenib to enhance the efficacy of HCC treatment.

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“…9 These point mutations are À55 C > A and À65 C > T substitution in the proximal HNF-1 binding site and À119 G > A substitution in distal HNF-1 binding site. 10 Owing to these point mutations, there is overbinding of HNF-1 to AFP gene and relative underbinding of NF-1, leading to AFP overproduction. 4 HPAFP was first time described in 1983 during an antenatal screening program for spina bifida in pregnant women by Ferguson-Smith et al 3 Our cases are unique that they all had high AFP in the background of chronic liver disease including cirrhosis.…”

Section: Discussionmentioning

confidence: 99%