Abstract
Fetuin-A (AHSG) is a multifunctional secretory protein and acts as an ectopic valve and artery calcification inhibitor. We assessed the correlation between serum levels of Fetuin-A and both exon 6 (248 C/T) and exon 7 (256 C/G) mutations in patients with coronary artery calcification (CAC), mitral annular calcification (MAC), and aortic valve calcification (AVC). 184 patients and 184 healthy individuals as control group were included. The genetic variants of rs4917 and rs4918 for the AHSG gene were determined by PCR-RFLP and T-ARMS PCR techniques. Fetuin-A levels, fasting blood sugar (FBS), urea, creatinine, calcium phosphorus, and lipid profile were measured. Fetuin-A levels were remarkedly lower in individuals with AVC, MAC, and CAC comparing to the control group (p < 0.001). The CT + TT genotypes and the T allele (AHSG Thr248Met) were associated with the risk of calcification of heart valves and coronary artery by 1.31 and 1.27 times in the patient group, respectively. The frequency of CT genotype and T allele was considerably higher in the patient group comparing to the control group. Patients with T allele (CT + TT) had higher levels of FBS, urea, low-density lipoproteins (LDL)-C, phosphorus, systolic blood pressure (SBP), diastolic blood pressure (DBP) while decreased levels of triglyceride, high-density lipoproteins (HDL)-C, calcium and fetuin-A in comparison to control group. Additionally, there was a positive correlation between serum FBS, urea, creatinine, HDL-C, calcium with fetuin-A, and a negative correlation between phosphorous level, SBP, and DBP with fetuin-A. T allele in rs4917 Single nucleotide polymorphism (SNP) is the risk allele of calcification of heart valves and coronary arteries and fetuin-A levels correlates negatively with the occurrence of the disease.
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Abbreviations
- AHSG:
-
α2-Heremance-Schmid –glycoprotein
- AVC:
-
Aortic valve calcification
- BMI:
-
Body mass index
- CAC:
-
Coronary artery calcification
- CPPs:
-
Calciprotein particles
- DBP:
-
Diastolic blood pressure
- FBS:
-
Fasting blood sugar
- HDL:
-
High-density lipoprotein
- LDL:
-
Low-density lipoprotein
- MAC:
-
Mitral annular calcification
- PCR:
-
Polymerase chain reaction
- RFLP:
-
Restriction fragment length polymorphism
- SBP:
-
Systolic blood pressure
- SNP:
-
Single nucleotide polymorphism
- TG:
-
Triglyceride
- WT:
-
Wild type
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Acknowledgements
This work was performed in partial fulfillment of the requirements for the biochemistry MSc thesis of Ehsan M. Noori, in the school of medicine, Kermanshah University of Medical Sciences, Kermanshah, Iran. The authors gratefully acknowledge the Research Council of Kermanshah University of Medical Sciences (Grant Number: 95005) for financial support.
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Mohammadi-Noori, E., Salehi, N., Mozafari, H. et al. Association of AHSG gene polymorphisms with serum Fetuin-A levels in individuals with cardiovascular calcification in west of Iran. Mol Biol Rep 47, 1809–1820 (2020). https://doi.org/10.1007/s11033-020-05275-z
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DOI: https://doi.org/10.1007/s11033-020-05275-z