Association of the NRF2 rs6721961 Polymorphism with Serum Vitamin E Levels in Idiopathic Male Infertility: A Case-Control Study among Iraqi Men
Noor Kamil Hussein AL-Mayahy *
Department of Medical Biotechnology, College of Biotechnology, Al-Qasim Green University, Babylon, Iraq.
Mohammed Talib Al-Tameemi
Department of Medical Biotechnology, College of Biotechnology, Al-Qasim Green University, Babylon, Iraq.
*Author to whom correspondence should be addressed.
Abstract
Background: Oxidative stress plays an important role in the pathogenesis of idiopathic male infertility. The transcription factor NRF2 regulates antioxidant defence genes, and polymorphisms in its promoter region may affect antioxidant capacity. Vitamin E (α-tocopherol) is a major lipid-soluble, chain-breaking antioxidant that protects sperm membranes from peroxidative damage.
Objective: This study aims to evaluate the frequency of the rs6721961 (−617 C>A) polymorphism in the NRF2 gene and its association with serum vitamin E levels in Iraqi men with idiopathic infertility.
Methods: This case-control study included 160 men (80 infertile patients and 80 fertile controls). The rs6721961 polymorphism was genotyped using tetra-primer ARMS-PCR, and serum vitamin E levels were measured using a validated colourimetric assay. Statistical analyses included chi-squared tests for genotype distributions, Mann-Whitney U tests, Kruskal-Wallis H tests, and Spearman's rank correlation.
Results: The rs6721961 A allele was significantly more frequent among infertile patients than among controls (46.9% vs. 16.9%; OR = 4.35, 95% CI: 2.59–7.29; p < 0.001). The AA genotype was detected only in the infertile group (21.3% vs. 0.0%). Overall serum vitamin E levels were significantly lower in infertile patients than in controls (p < 0.001). Within the patient group, serum vitamin E concentrations decreased across the CC, CA, and AA genotypes, although the between-genotype comparison was not statistically significant (p = 0.080). Spearman's analysis nevertheless showed a significant inverse correlation between the number of A alleles and serum vitamin E levels (ρ = −0.373, p < 0.001).
Conclusion: The rs6721961 A allele and AA genotype were associated with idiopathic male infertility and lower serum vitamin E levels in this Iraqi population. The inverse association between A-allele dosage and serum vitamin E may indicate a relationship between NRF2 variation and antioxidant status; however, larger studies and functional validation are required before clinical implications can be established.
Keywords: NRF2, NFE2L2, rs6721961, vitamin E, idiopathic male infertility, oxidative stress, antioxidant status, genetic polymorphism