DOI: 10.4103/bbrj.bbrj_98_26 ISSN: 2588-9834
Combined Effects of Methylenetetrahydrofolate Reductase C677T Polymorphism, Promoter Hypermethylation, Increase the Risk of Asthenozoospermia in Jordanian Men
Osamah Batiha, Manal Essam Abu Alarjah, Hala Khanjar, Mazhar Al Zoubi, Mohammad Altalib, Mohammad A. Al Smadi, Esra’a Al-Zoubi, Diana Almahdawi Abstract
Background:
Methylenetetrahydrofolate reductase (
MTHFR)
variants and promoter methylation may influence folate metabolism and sperm motility. This study investigated the associations between the
MTHFR
C677T polymorphism and promoter methylation status in Jordanian males diagnosed with asthenozoospermia.
Methods:
A case–control study included 101 blood and semen samples (53 asthenozoospermic/cases, 48 normozoospermic/controls) collected from the Prince Rashed Bin Al-Hasan Military
In Vitro
Fertilization Unit. Polymerase chain reaction (PCR) and restriction fragment length polymorphism were used to genotype the
MTHFR
C677T polymorphism. Methylation-specific PCR was used to determine the methylation status. Fisher’s exact test, Mann–Whitney
U
-test, and binary and multivariable logistic regression were used as appropriate.
Results:
Asthenozoospermic men showed significantly lower progressive sperm motility than normozoospermic controls. Furthermore, significant differences were observed in the distribution of
MTHFR
C677T genotypes between groups (
P
= 0.014), with CT/TT genotypes were more frequent among cases. After adjustment for age, physical activity, and smoking; the unmethylated promoter was associated with greater odds of belonging to the control group (odds ratio [OR] = 3.35; 95% confidence interval [CI]: 1.24–9.04;
P
= 0.017), while the odds for the CC genotype belonging to the control group was almost double compared to the cases (OR = 2.17; 95% CI: 0.98–9.04;
P
= 0.054). In the combined model, promoter methylation remained independently associated with diagnosis (OR = 3.12; 95% CI: 1.138–8.546;
P
= 0.027), whereas
C677T
genotypes did not reach statistical significance (OR = 1.93; 95% CI: 0.800–4.67;
P
= 0.143).
Conclusions:
The findings suggest that
MTHFR
promoter hypermethylation is a significant predictor of asthenozoospermia in Jordanian men, while the C677T variant showed a group-level association but was not a significant predictor in the combined analysis, emphasizing the role of epigenetic and genetic factors in sperm motility.