Abstract
BackgroundVariants in the Methylenetetrahydrofolate reductase (MTHFR) gene may result in a lowered catalytic activity and associate with subsequent elevated serum homocysteine (Hcy) concentration, abnormal DNA synthesis and methylation, cardiovascular risk, and unhealthy aging. Several investigations on the relationship of MTHFR C677T polymorphism with serum lipid profile and longevity have been conducted in some populations, but the findings remain mixed. Herein, we sought to look at the association between MTHFR C677T and lipid profile in a longevous cohort in Bama, a well-known home of longevity in China.MethodsGenotyping of MTHFR C677T was undertaken in 516 long-lived inhabitants (aged 90 and older, long-lived group, LG) and 493 healthy controls (aged 60–75, non-long-lived group, non-LG) recruited from Bama area. Correlation between MTHFR genotypes and lipids was then evaluated.ResultsT allele and TT genotype were significantly more prevalent in LG (P = 0.001 and 0.002, respectively), especially in females, than in non-LG. No difference in the tested lipid measures among MTHFR C677T genotypes was observed in LG, non-LG and total population (P > 0.05 for all). However, female but not male T carriers exhibited higher TC and LDL-C levels than did T noncarriers in the total population and in LG after stratification by sex (P < 0.05 for each). These differences did not however remain through further subdivision by hyperlipidemia and normolipidemia.ConclusionThe higher prevalence of MTHFR 677 T genotypes and its modest unfavorable impact on lipids in Bama long-lived individuals may imply an existence of other protective genotypes which require further determination.
Highlights
Methylenetetrahydrofolate reductase (MTHFR) catalyses the conversion of 5,10-methylenetetrahydrofolate to 5-methyltetrahydrofolate, the methyl donor which remethylates homocysteine (Hcy) to methionine [1]
Methionine is the immediate precursor of S-adenosylmethionine (SAM), the universal methyl donor of numerous biological methylation reactions that are essential to the synthesis of DNA, proteins, phospholipids and various neurotransmitters [2]
We designed the present study to test the hypothesis that the MTHFR C677T polymorphism is associated with different serum lipid profiles and may partially account for the longevity in Bama nonagenarians/centenarians of Zhuang ethnic origin
Summary
Methylenetetrahydrofolate reductase (MTHFR) catalyses the conversion of 5,10-methylenetetrahydrofolate to 5-methyltetrahydrofolate, the methyl donor which remethylates homocysteine (Hcy) to methionine [1]. Hcy concentration (hyperhomocysteinemia) can in the main be ascribed to vitamin deficiency (e.g. folate, B12 and B6), renal dysfunction, aging or a common variance to the MTHFR gene, in which cytosine is replaced by thymidine (C > T) at base position 677. This single nucleotide polymorphism (rs1801133) causes an alanine-to-valine substitution in the MTHFR protein at polypeptide position 222 that renders the enzyme more thermolabile and less active as compared to the wild-type enzyme [12]. We sought to look at the association between MTHFR C677T and lipid profile in a longevous cohort in Bama, a well-known home of longevity in China
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