Association between SOD2 T-9C and MTHFR C677T polymorphisms and longevity: a study in the Jordanian population

Omar F. Khabour*, Essa S. Abdelhalim, and Ahmad Abu-Wardeh

Address: Department of Medical Laboratory Sciences, Jordan University of Science and Technology, Irbid 22110, Jordan

Email: Omar F. Khabour* - khabour@just.edu.jo; Essa S. Abdelhalim - watan48@yahoo.com; Ahmad Abu-Wardeh - ams_just_scholarship@yahoo.com

* Corresponding author

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Background: Aging in animals is associated with high body oxidative stress, which might affect susceptibility and onset of age-related diseases, and the subsequent lifespan. Therefore, genes that modulate oxidative stress might play a role in determining longevity. In this study, we investigated whether the gene pool relevant to the SOD2-9T/C and MTHFR 677C/T polymorphisms changes as the Jordanian population ages.

Methods: Polymorphisms were genotyped in 130 elderly subjects (57 females and 73 males, mean age: 90.01 years) and 135 young control subjects (67 females and 68 males, mean age: 33.43 years).

Results: No significant differences were found in the genotype and allele frequencies of examined SOD2 and MTHFR gene variants between the elderly group and young controls (P > 0.05), nor when each gender was considered separately (P > 0.05). SOD2-9T/C and MTHFR 677C/T gene polymorphisms do not seem to be important in the Jordanian population for the longevity phenotype.

Background

Superoxide anion is dismutated by SOD2 into hydrogen peroxide, which is detoxified into water by glutathione peroxidases and catalase [5]. The presence of the C allele at the -9 position of the SOD2 gene results in substitution of alanine for valine (Ala16Val) in the mitochondrial targeting sequence [6]. This substitution partially retains SOD2 enzyme within the narrow inner membrane import pore and lowers the enzyme activity [7,8]. The importance of the SOD2-9T/C polymorphism is indicated by its association with several age-related diseases such as cancer [9,10] and diabetic nephropathy [11].

Aging involves increases in oxidative stress status presented by elevated levels of oxidized forms of biomolecules in the body of the organism [1]. This leads to tissue damage and decreases in body functions, homeostasis, and tolerance to chronic diseases [2,3]. Thus, genes that modulate oxidative stress might play a role in human longevity.

In this study, we investigated the association of SOD2-9T/C SNP and MTHFR 677C/T SNP with longevity in the Jordanian population. The SOD2 gene codes for mitochondrial manganese superoxide dismutase, a major cellular antioxidative stress enzyme [4]. MTHFR codes for methylenetetrahydrofolate reductase that catalyzes the conversion of 5,10-methylenetetrahydrofolate to 5-methyltetrahydrofolate. The latter serves as a methyl donor in the reaction converting homocysteine to methionine [12].

The T allele at position 677 of the MTHFR gene causes substitution of alanine to valine and the resulting decrease in enzyme activity and increase in body homocysteine concentrations [13]. Excess homocysteine undergoes auto-oxidation in plasma, so that free oxygen radicals are produced thereby enhancing endothelial tissue damage and inflammation [14]. In addition, excess homocysteine can directly impair DNA methylation, resulting in altered gene expression [15]. The MTHFR 677C/T polymorphism has been shown to be associated with ischemic stroke [16], cancer [17], and coronary artery disease [18].