OnLine Journal of Biological Sciences 6 (1): 28-34, 2005 ISSN 1608-4217 © 2005 Science Publications Corresponding Author: Salvatore Musumeci, Department of Pharmacology, Gynecology, Obstetrics and Pediatrics, University of Sassari, Viale San Pietro 43b 07100 Sassari, Italy. Tel: 0039.360285505 Fax: 0039.0957179690 e-mail: smusumeci@tiscalinet.it 1 Methylenetetrahydrofolate reductase (MTHFR) from Mediterranean to sub-Saharan areas. Rosa Chillemi 1 , Andrea Angius 2-3 , Ivana Persico 3 , Alessandro Sassu 3 , Dionigio Antonio Prodi 3 , Jacques Simpore 4 , Salvatore Musumeci 2-5 1 Department of Chemical Science, University of Catania, Italy ; 2 Institute of Population Genetics, CNR, Porto Conte (SS), Italy; 3 Shardna Life Sciences, Cagliari, Italy; Centre Medical St Camille, Ouagadougou, Burkina Faso 4 5 Department of Pharmacology, Gynecology and Obstetrics, Pediatrics, University of Sassari, Italy Abstract: There are differences in the allele frequency of MTHFR polymorphism between Western and African population. The aim of this study is to determinate the prevalence of MTHFR C677T and A1298C polymorphisms in young and old people living in different areas from Mediterranean to sub-Saharan areas. The observed vs expected genotype frequencies of 677T were in Hardy Weinberg equilibrium, with the exception of old Sardinian subjects (P=0.02). Calculation of 677T allele frequency in young and old African subjects (8% and 3%, respectively) indicated that the 677T allele was disadvantaged in old Africans (P=0.02). The difference among young and old Sardinians and Sicilians were not significant at the same degree (43% vs 37% P=0.07 and 46% vs 42% P=0.28, respectively). However, the reproducible trend that showed the prevalence of 677T allele in the young subjects of the three studied areas confirms the disadvantage of this polymorphism with the age. There was a significant difference (P=0.005) on the observed vs expected frequency of 1298C homozygosity in African old subjects compared to younger ones, while the observed vs expected genotype frequencies were in equilibrium in young and old Sardinian and Sicilian subjects. The frequencies of 1298C and 1298A alleles were comparable between young and old African, Sardinian and Sicilian subjects. The lower frequency of 677T allele in old African, Sardinian and Sicilian subjects compared to young ones and the absence of TT genotype among old African subjects, should be considered as a consequence of an elevated mortality of 677T carriers. Key words: MTHFR, Sardinia, Sicily, Burkina Faso, Young people, Old people, Nutrition, Folic acid, Malaria _____________________________________________________________________________________________ INTRODUCTION Methylenetetrahydrofolate reductase (MTHFR) catalyzes the conversion of 5,10- methylenetetrahydrofolate to 5-methyltetrahydrofolate, which is needed for methionine synthase to convert homocysteine (Hcy) to methionine (Scriver et al. 1995). Its key function in Hcy metabolism makes this enzyme a hot point in the mechanism which associates hyperhomocysteinemia (HHcy) with the cardiovascular risk and other pathologies where the role of folate is largely documented (Mayer et al., 1996). The MTHFR gene is polymorphic, with single nucleotide variants within codon 677 in exon 4 (CT), which causes an alanine to valine substitution, and within codon 1298 in exon 7 (AC) which determines a substitution of glutamate by an alanine residue (Botto et al., 2000; James, 2000). The codon 677 variant encodes a thermolabile enzyme with reduced activity that leads to an increase of plasma Hcy level (Gemmati et al., 1999). Individuals who are homozygous for the codon 677 polymorphism show hypomethylation of DNA in peripheral blood leukocytes, an effect that is especially pronounced when folate levels are low (Botto et al., 2003). In western countries the C677T polymorphism may result in the necessity to have a higher folate ingestion to reduce the plasma HHcy and it has been considered, especially in North Europe, a risk factor responsible of neural tube defects and 21 trisomy (Botto and Yanget, 2000; Botto et al., 2003; Sheth and Sheth, 2003). The homozygosity CC for 1298 polymorphism becomes a risk factor of vascular disorders, especially with the individual’s aging, if associated with a decreased ingestion of folate (Spotila et al., 2003). Also