Effects of Gender Differences in MTHFR 677C > T and Homocysteine Level on the Occurrence of Adverse Pregnancy...

Background: The MTHFR 677C > T polymorphism in women has been associated with an increased risk of deep venous thrombosis and adverse pregnancy outcomes (APOs). However, research concerning its effects in men remains limited. Methods: This study examined 662 adults with a history of pregnancies affected by chromosomal abnormalities (CAs: 343 females and 319 males), 137 adults with a history of pregnancies affected by cleft lip and palate (CLP: 71 females and 66 males), and 133 adults with a history of biochemical pregnancies (BPs: 65 females and 68 males), forming three case groups. A control group of 339 adults without APOs (221 females and 118 males) was studied. The genotypes of the MTHFR 677C > T polymorphism and Hcy levels were analyzed for all participants. Results: Elevated Hcy levels were identified as a risk factor for CA, CLP, and BP in both adult females and males. The MTHFR 677C > T polymorphism was a risk factor for CA, CLP, and BP in females, whereas in males, it was a risk factor for CA and BP, but not for CLP. Individuals with the TT genotype exhibited the highest Hcy levels compared to those with CC and CT genotypes, across both genders and all groups. Males exhibited significantly higher Hcy levels and a significantly greater incidence of hyperhomocysteinemia compared to females across all groups. Conclusions: The MTHFR 677C > T polymorphism was a gender-dependent risk factor for fetal CLP but was gender-independent for BP and fetal CA. Elevated Hcy levels were a gender-independent risk factor for BP, CLP, and CA. Individuals with the MTHFR 677TT genotype were more likely to have elevated Hcy levels, and there were notable gender differences in Hcy levels and hyperhomocysteinemia incidence.