02319nas a2200301   4500000000100000008004100001260001600042653001900058653001900077653001100096653003500107653003600142653001600178100002400194700001300218700002100231700002300252700001300275700001600288700002000304700001200324700002300336245009200359300001000451490000700461520153500468022001402003       2013                            d  c2013 Nov 3010aFetal Diseases10aGene Frequency10aHumans10aNitric Oxide Synthase Type III10aPolymorphism, Single Nucleotide10aThalidomide1 aSales Luiz Vianna F1 aFraga LR1 aTovo-Rodrigues L1 aTagliani-Ribeiro A1 aBiondi F1 aMaximino CM1 aSanseverino MTV1 aHutz MH1 aSchüler-Faccini L00aPolymorphisms in the endothelial nitric oxide synthase gene in thalidomide embryopathy.  a89-920 v353 a<p>Thalidomide is one of the most potent teratogens known to humans. It is currently used for many clinical situations such as treatment of leprosy reactions and multiple myeloma. However, the teratogenic mechanisms by which it produces morphological defects still remain unclear. One of the hypotheses is the blockage of angiogenesis by reduction of nitric oxide (NO). In this study, we evaluated two functional polymorphisms of the endothelial nitric oxide synthase (eNOS) gene which is a constitutively expressed enzyme responsible for production of NO. The promoter -786T>C exon 7 (896G>T) polymorphisms were genotyped using real-time PCR for 28 individuals with thalidomide embryopathy (TE), 27 first-degree relatives of these individuals, and 68 individuals from the general population. Their allele, genotypic, and haplotypic frequencies were compared. A significant difference was observed in the -786T>C polymorphism genotypes (p=0.03) between the groups affected by TE and those unaffected (non-relatives). The TT genotype of the 896G>T polymorphism was observed in 10.7% of those affected and 2.9% of those unaffected, but the difference was not statistically significant (p=0.09). The haplotypic analysis indicated that the wild haplotype -786T/896G was distributed differently in the affected and unaffected groups (p=0.004). These results indicate that the individuals with TE have a higher frequency of alleles associated with lower expression of eNOS, indicating that this may be a genotype susceptible to TE. </p>  a1089-8611