Dipartimento di Biochimica, Biologia e Genetica, Universita Politecnica delle Marche, Ancona, Italy
Homocysteine (Hcy) pathway. In humans, the only source of Hcy is the demethylation of methionine, through several methyl transferase activities, such as NNMT. Hyperhomocysteinemia is a condition characterized by high plasma level of Hcy and it is implicated in several diseases, as Alzheimer and other clinical status such as atherosclerosis, ischemic strokes (Furie et al., 2006) and osteoporosis. The causes of hyperhomocysteinemia are both genetic and environmental (e.g.: life-style, sex, age), but genetic basis are still poorly understood. Different studies have investigated an association of NNMT polymorphisms with hyperhomocysteinemia. Souto (Souto et al., 2005) carried out the GAIT (Genetic Analysis of Idiopathic Thrombophilia) Project in a Spanish population, where 10 SNPs of NNMT gene were investigated. The results of this study suggested a strong correlation between plasma Hcy level and a specific haplotype. Because these genetic variants are in non-coding regions, they could influence the regulation of transcription but evidence on the functionality of the NNMT polymorphisms is still conflicting.
A consistent study was carried out by Ling Zhang (Zhang et al., 2007) in about three hundred healthy japanese workers. Authors focused on a specific NNMT polymorphism (rs694539) localized in the first intron. The results confirmed that SNPs in non-coding regions affected the regulation of transcription, but they werent the main determinant of the plasma Hcy levels, because other factors were involved: age, sex, plasma folate levels and the associations with MTHFR polymorphisms.
The association between NNMT polymorphisms and hyperhomocysteinemia has been investigated by Bathum (Bathum et al., 2007). Six hundred and three danish adult twin pairs were included in the study. Experimental results suggested that MTHFR C677T is the only SNP responsible for the disease progression, leaving only minor influence to other genetic variations.
Monica Emanuelli ; Monia Cecati ; Davide Sartini ; Valentina Pozzi
NNMT (nicotinamide N-methyltransferase)
Atlas Genet Cytogenet Oncol Haematol. 2009-07-01
Online version: http://atlasgeneticsoncology.org/gene/44506/nnmt-(nicotinamide-n-methyltransferase)