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Distribution of Methionine Synthase Reductase (MTRR) Gene A66G Polymorphism in Indian Population
Upendra Yadav1, Pradeep Kumar1, Vandana Rai1
1Human Molecular Genetics Laboratory, Department of Biotechnology, VBS Purvanchal University, Jaunpur, 222003 India.
Abstract:
Methionine synthase reductase (MTRR) is an important enzyme of the folate/homocysteine pathway. It is responsible for regulation of methionine enzyme by reductive methylation. A common variant A66G is reported in the FMN-binding domain of the MTRR gene, which leads to substitution of isoleucine by methionine (I22M) in MTRR enzyme with reduced activity. Reduced catalytic activity of enzyme leads to high homocysteine concentration in blood and increases risk for numerous diseases. The frequency of A66G polymorphism varies in different ethnic groups. The present study has been designed to evaluate the frequency of MTRR A66G gene polymorphism in the Eastern UP population by PCR-RFLP method. Along with this we also performed a meta-analysis to evaluate the global prevalence of this polymorphism. Databases were screened to identified the eligible studies. The prevalence of the G allele and GG genotype was determined by the use of prevalence proportion with 95% CI. Open meta-analyst software was used for the meta-analysis. Total 1000 blood samples were analyzed, the frequencies of A and G alleles were 0.35 and 0.65 respectively. Meta-analysis results revealed that the prevalence of G allele and GG genotype were 49.4% (95% CI 40.6-58.1, p ≤ 0.001) and 24.3% (95% CI 17.8-30.9, p ≤ 0.001) respectively. In sub-group meta-analysis, the lowest frequency of G allele was found in South America (32.7%; 95% CI 14.1-51.3, p ≤ 0.001), and highest in Asia (56.4%; 95% CI 39.5-73.3, p ≤ 0.001). The results of the meta-analysis showed that the Asian population has the highest frequency of G allele and highest frequency of the GG genotype was found in the European population.
Insights
Methionine synthase reductase (MTRR) A66G polymorphism, linked to reduced enzyme activity and increased disease risk, shows varying global frequencies. Asian populations exhibit the highest G allele prevalence, while Europeans show the highest GG genotype frequency.
Area of Science:
- Genetics
- Biochemistry
- Population Health
Background:
- Methionine synthase reductase (MTRR) regulates the folate/homocysteine pathway.
- A common MTRR gene variant (A66G) results in a less active enzyme (I22M), potentially increasing homocysteine levels and disease risk.
Purpose of the Study:
- To determine the frequency of the MTRR A66G polymorphism in the Eastern Uttar Pradesh population.
- To conduct a global meta-analysis evaluating the prevalence of this polymorphism across diverse ethnic groups.
Main Methods:
- Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP) was used to analyze MTRR A66G in 1000 samples.
- A systematic literature review and meta-analysis using OpenMeta-analyst software assessed global prevalence data.
Main Results:
- The study found MTRR allele frequencies of 0.35 (A) and 0.65 (G) in the Eastern UP population.
- Global meta-analysis revealed a G allele prevalence of 49.4% and GG genotype prevalence of 24.3%.
- Subgroup analysis indicated the lowest G allele frequency in South America (32.7%) and the highest in Asia (56.4%).
Conclusions:
- The MTRR A66G polymorphism is prevalent globally, with significant variations across populations.
- Asian populations show the highest frequency of the G allele, while European populations exhibit the highest frequency of the GG genotype.
- Understanding the geographic distribution of this polymorphism is crucial for assessing population-specific health risks associated with homocysteine metabolism.
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