Thrombosis and Risk FactorsI read the comment of Toprak et al. on my letter tothe Editor appeared in a recent issue of the journal withgreat interest [1]. They pointed a missing point in my letterand then focused on the effect of folate metabolism onhomocysteine and metihelenetetrahydrofolate gene polymorphismat 677 C to T extensively [1]I would like to express my thanks to Toprak et al. givinga chance to explain my view on this matter once more.As it is well known that there is a continuing debateon homocysteine metabolism, MTHFR SNP’s and folatemetabolism and there are several published reviews onthis subject not reaching to a conclusion.Recently we reported that MTHFR 677 T has an influenceon Hcy levels in Turkish population. But also wefound another possible MTHFR gene haplotype, whichdoes not have an effect on Hcy levels [2].Furthermore, there are also rare novel SNPs publishedwithin the MTHFR 677 region with an allele frequencyof 1 in 3000-4000 sample, including MTHFR 678 C-A(Ala222Ala) in Turkish population [3,4,5] which may leadto erroneous technical reporting.Since our first publication on homocysteine relatedgene polymorphisms in Turkish population in 1998 [6], and the others following the first paper, I reached to aconclusion that without determining homocysteine levels,analyzing MTHFR 677C-T solely at the DNA levelis unnecessary, not cost effective and does not have anyclinical value especially in Turkish population.So, only homocysteine levels should be routinely analyzedand not the MTHFR 677 T SNP alone. If any causeof high homocysteine levels could not be found, thenMTHFR 677 T analysis can be performed.