C677T polymorphism of the MTHFR gene and variant hemoglobins: a study in newborn s f rom Salvador, Bahia, Brazil Polimorfismo C677T no gene da MTHFR e hemoglobinas variantes: um estudo em recém-nascidos de Salvador, Bahia, Brasil

The C677T polymorphism in the methylenetet ra h y d rofolate reductase gene (MTHFR) is associated with an increase in total homocysteine serum levels (tHcy), described as a risk factor for c a rd i ovascular disease. Eight hundred fort y t h ree neonates from two different maternity h o sp i t a l s , one public and another priva t e , in Salva d o r, Ba h i a , Brazil were screened for this polymorphism by PCR and RFLP. The T-allele frequency in the total sample was 0.23, and the p re valence rates of heterozygous and homoz ygous carriers were 36.2% and 5.3%, re s p e c t i ve l y. The T-allele frequency differed and the T/T g e n otype was more pre valent at the private maternity hospital. The hemoglobin (Hb) profile was investigated by HPLC in 763 new b o r n s . The frequency of variant Hb was higher at the public than at the private maternity hospital. The association of the C677T polymorphism and the Hb profile was investigated in 683 new b o r n s , s h owing a re l a t i vely high frequency of va r i a n t Hbs and the T allele. These data could prov i d e an important basis for further studies focusing on potential risks of va s o o c c l u s i ve events in these individuals. Newborns In f a n t ; Po l y m o r p h i s m ; He m o g l o b in o p a t h i e s I n t ro d u c t i o n Me t h y l e n e t e t ra h yd rofolate reductase (MTHFR) is a key enzyme in folate and homocysteine (Hcy) metabolism. A single point mutation c a u sing a C → T substitution at nucleotide 677 of the MTHFR gene has been associated with a t h e rmolabile enzyme form of low biological activity 1. High total homocysteine (tHcy) seru m or plasma levels have been attributed to the p resence of the C677T MTHFR polymorphism, mainly in association with low folate and vitamin B12 levels 2 , 3 , 4. The role of high tHcy seru m or plasma levels re c e i ved considerable intere s t after these factors we re implicated as an imp o rtant risk factor for card i ovascular disease in a study examining childre n’s aorta fragments 5; the study proposed that high homocysteine l e vels play a role in art e ri o s c l e rosis genesis. Sickle-cell anemia (SS) is a monogenic diso rder with worldwide distribution and high p re valence in Brazil 6. The mutant sickle hemoglobin results from a single nucleotide substitution: (GAG → GTG) at the sixth codon of the beta-globin gene. Sickle cell anemia displays a h e t e rogeneous clinical presentation, unpredictable clinical development, and is chara ct e ri zed by chronic hemolytic anemia and va s o o c c l u s i ve events that result in acute pain cri s e s, with chronic and pro g re s s i ve tissue damage 7. Vascular alterations are commonly observe d among these patients 8, and SS and SC disease Couto FD et al. 5 3 0 Cad. Saúde Pública, Rio de Janeiro, 20(2):529-533, mara b r, 2004 c a r riers have an increased risk of art e rial va scular disease and venous thrombosis 9. The high turn over of red blood cells (RBC) o b s e rved in sickle-cell patients is associated with lower serum levels of folate and vitamin B12 1 0, leading to the increased tHcy serum or plasma levels that have been implicated in va scular endothelium injury 1 1. Even in the absence of genetic predisposition or tra d i t i o n a l risk factors such as C-re a c t i ve protein and MTHFR, the increased tHcy levels have been c o n s i d e red an important predictor of mort a l i t y in patients with angiographically defined coron a ry art e ry disease 1 2. Bahia, a State in No rtheast Brazil, has a high interethnic admixture. The strong Afri c a n gene pool 1 3 has resulted in a high fre q u e n c y of hemoglobinopathies, with a pre valence of S h e te rozygotes (AS) reaching 14% in groups of A f rican descendants 1 4. In this article we re p o rt on a molecular chara c t e rization of the C677T MTHFR gene polymorphism in a newborn p o pulation from two different maternity hospitals in Sa l va d o r, investigating its association with the presence of va riant hemoglobins. Material and methods