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[ANALYSIS OF THE ASSOCIATION BETWEEN THR83ALA POLYMORPHISM OF MATRIX GLA-PROTEIN GENE AND LOWER EXTREMITY ARTERIAL
Yu Ataman1, Т Еrmolenko1, A Grek2
1Sume State University, Medical Institute, Department of Family and Social Medicine, Department of Internal Medicine; Department of Surgery and Pediatric Surgery with the course of Urology, Ukraine.
Insights
The Thr83Ala polymorphism in the matrix Gla-protein (MGP) gene is linked to lower extremity arterial calcification (AC). This MGP gene variant appears to reduce AC risk specifically in Ukrainian women.
Area of Science:
- Genetics
- Cardiovascular Disease
- Biochemistry
Background:
- Lower extremity arterial calcification (AC) is a significant factor in cardiovascular disease pathogenesis.
- The matrix Gla-protein (MGP) gene, specifically its Thr83Ala polymorphism, has been implicated in the development of AC.
Purpose of the Study:
- To investigate the association between the MGP gene's Thr83Ala polymorphism (rs 4236) and arterial calcification (AC).
- To analyze this association in both male and female subjects within the Ukrainian population.
Main Methods:
- Genotyping of the MGP exon 4 Thr83Ala polymorphism using polymerase chain reaction and restriction fragment length polymorphism analysis.
- Comparison of allele and genotype frequencies between 40 patients with AC and 40 healthy controls from Ukraine.
Main Results:
- The Thr83Ala polymorphism may alter MGP's functional and anticalcinogenic properties.
- No significant overall association was found between MGP Thr83Ala polymorphism and AC (p=0.352).
- However, AC was less frequent in women with the Ala/Ala genotype compared to men with the same genotype (p=0.036).
Conclusions:
- The substitution of threonine by alanine in the MGP gene (Thr83Ala polymorphism) is associated with a reduced likelihood of arterial calcification in Ukrainian females.
- This suggests a potential sex-specific protective effect of this MGP genotype against arterial calcification in this population.
Abstract:
Lower extremity arterial calcification (AC) is a common pathological process that has independent significance in the pathogenesis of many cardiovascular diseases. There is evidence that development of AC associated with Thr83Ala polymorphism of matrix GLA-protein gene. The objective of this study was to examine the association between Thr83Ala polymorphism of matrix Cla protein (MGP) gene and AC in male and female subjects of the Ukrainian population. 40 AC and 40 healthy controls were recruited to the study. MGP exon 4 Thr83Ala polymorphism (rs 4236) was examined using the polymerase chain reaction with subsequent restriction fragment length polymorphism analysis. The obtained data show that the substitution of threonin by alanine at position 83 in a molecule of MGP can affect its functional characteristics and anticalcinogenic properties. The distribution of homozygous carriers of a major allelic variant, and heterozygous and homozygous minor allele variants of Thr83Ala polymorphism in patients with AC was 40,0%, 47,5%, and 12,5% respectively. The corresponding distribution of variants in the control group was 32,5%, 42,5% and 25,0% (p=0,352 by χ2 -test). In women who are carriers of Ala/Ala-variant, CA occurs more rarely than in men with the same genotype (p=0,036 by χ2 -test). The substitution of threonine by alanine due to MGP exon 4 Thr83Ala polymorphism is related to a decrease in the likelihood of CA in female persons in the Ukrainian population.
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