MTHFR polymorphisms and serum cobalamin affect plasma homocysteine concentrations differentially in females and males

Abstract

A total of 523 subjects (297 females and 226 males) from the Canary Islands Nutrition Study (ENCA) were studied in order to examine the effect of the MTHFR 677C>T, 1298A>C and 1793G>A polymorphisms, adjusted for age, serum (S)‑folate and S‑cobalamin levels, on total plasma homocysteine concentrations (tHcy). Genotyping was performed with Pyrosequencing® technology. The MTHFR 677T‑allele was associated with increased tHcy concentrations only in males (P=0.005). The MTHFR 1298C‑allele was found to be associated with higher tHcy levels but similarly, only in males (P=0.025). The MTHFR 1793A‑allele was associated with decreased tHcy concentrations in the younger males (P=0.042). A haplotype‑based approach was marginally superior in explaining the genetic interaction of the MTHFR polymorphisms on tHcy plasma levels (R2 0.352 vs. 0.342 for a simple genotype‑based approach). A nutrigenetic interaction between the MTHFR 677C>T genotype and S‑cobalamin on tHcy levels was demonstrated in both genders. The increase in tHcy was more pronounced with decreasing S‑cobalamin quintiles in 677TT homozygotes (P=0.005 for males and P=0.015 for females) than with decreasing S‑folate quintiles (P for trend not significant). It was concluded that gene‑nutrient interactions may differ depending on the sex and age of the subjects. The transferability of gene‑nutrient interactions from one community to others may therefore be limited not only by different food patterns but also by different ages, genders and genotype distributions.

Homocysteine and homocysteine-related compounds: an overview of the roles in the pathology of the cardiovascular and nervous systems

“…Numerous factors can affect the total plasma homocysteine (tHcy) levels in human plasma, such as gender (woman have lover tHcy than men), nutrition habits (diet deficient in folate, vitamin B 6 and B 12 leads to increment of tHcy), lifestyle habits (smoking, alcohol consumption, sedentary way of living) (Naik et al 2007;Nagele et al 2011;Nilsson et al 2014;Nygård et al 1995;Hildebrandt et al 2015;Jung et al 2015).…”

Genotype, B‐vitamin status, and androgens affect spaceflight‐induced ophthalmic changes

“…Another limiting factor is the small subset of SNPs selected for analysis. The 5 SNPs were selected because they are documented genetic determinants of circulating homocysteine concentrations (36)(37)(38), and homocysteine was a metabolite shown to be higher in astronauts with vision changes after longduration spaceflight (3). Ideally, SNPs of all enzymes of the 1-carbon pathway would have been studied.…”

Sex differences in the prevalence and clinical correlates of hyperhomocysteinemia in patients with bipolar disorder

“…The results of adult patients with epilepsy were contradictory (Dinç & Schulte, ). Some prior studies have also found that the MTHFR C677T mutation determined HHcy in patients with epilepsy receiving valproic acid (Ono, Sakamoto, Mizoguchi, & Sakura, ; Yoo & Hong, ), and the MTHFR 677T allele was found to be associated with increased Hcy levels only in males (Nilsson et al, ), suggesting that sex differences in a gene–drug interaction may lead to the changes of homologous system, which may provide reasonable explanations for conflicting results, and thus, further studies are needed to verify our findings.…”

“…The results of adult patients with epilepsy were contradictory (Dinç & Schulte, 2018). Some prior studies have also found that the MTHFR C677T mutation determined HHcy in patients with epilepsy receiving valproic acid (Ono, Sakamoto, Mizoguchi, & Sakura, 2002;Yoo & Hong, 1999), and the MTHFR 677T allele was found to be associated with increased Hcy levels only in males (Nilsson et al, 2014), suggesting that sex differences in a gene-drug interaction may lead to the changes of homologous system, which may provide rea- were given to patients based on their severity and type of mood episode (manic, depression, or mixed). However, we did not collect information on the corresponding drugs in different mood phase, as well as information on different dosage, duration of treatment, or in combination with other drugs.…”

“…The influence of estrogen on Hcy metabolism was independent of nutrition and muscle mass and may be a key reason for elucidating its sex-specific effects (Dimitrova et al, 2002). In addition, sex-linked genetic variation may contribute to sex differences in HHcy rates and higher Hcy levels in BD (Nilsson, Bottiger, Henriquez, & Serra Majem, 2014). Several polymorphism loci in methylenetetrahydrofolate reductase (MTHFR) gene, the key enzyme of Hcy metabolism, have been found to be associated with sex differences in total plasma Hcy concentrations (Barbosa et al, 2008;Hou et al, 2016).…”