Tumor necrosis factor-alpha promoter polymorphisms in Mexican patients with rheumatic heart disease.
The major histocompatibility genes (MHC) have been associated with the genetic susceptibility to rheumatic heart disease (RHD). Results have been inconsistent and new genes located on the MHC region such as tumor necrosis factor (TNF-alpha) need to be analyzed. TNF-alpha polymorphisms (positions -238 and -308) were determined in 87 RHD Mexican Mestizo patients and 101 healthy controls. Patients were classified into mitral valve damage (MVD) and multivalvular lesion (MVL) categories. TNF-238 G allele and GG genotype were increased in patients when compared to healthy controls (pC=0.001, OR=14.1 and pC=0.003, OR=14.1, respectively). Also, decreased frequencies of TNF-238 A allele (pC=0.001) and AG genotype (pC=0.003) were found. TNF-308 polymorphism analysis showed increased frequencies of T2 (A) allele (pC<10(-3), OR=10.8) and T1T2 (AG) genotype (pC<10(-3), OR=9.85) and decreased frequencies of T1 (G) allele and T1T1 (GG) genotype (pC<10(-3)). When comparing valvular damage to healthy controls, patients with MVD showed increased frequencies of -238 GG (pC=0.03, OR=ND), -308 T1T2 (AG) (pC<10(-3), OR=14) and -308 T2 (A) (pC<10(-3), OR=11.7). Also, this group showed decreased frequencies of T1 (G) allele and T1T1 (GG) genotype (pC<10(-3)). Patients with MVL presented increased frequency of -308 T2 (A) allele (pC=0.0003, OR=8.65) and decreased frequencies of -308 T1 (G) allele and -308 T1T1 (GG) genotype (pC=0.0003 and pC=0.006, respectively). Distribution of -238 and -308 polymorphisms were similar between MVD and MVL. The data demonstrate that RHD is associated with TNF-alpha polymorphisms in the Mexican population; however, these polymorphisms do not have relation with the valve damage.
Hernández-Pacheco
Guadalupe
G
Department of Physiology, Instituto Nacional de Cardiología Ignacio Chávez, Juan Badiano No. 1, Tlalpan 14080, Mexico City, Mexico.
Flores-Domínguez
Carmina
C
Rodríguez-Pérez
José Manuel
JM
Pérez-Hernández
Nonanzit
N
Fragoso
José Manuel
JM
Saul
Angela
A
Alvarez-León
Edith
E
Granados
Julio
J
Reyes
Pedro A
PA
Vargas-Alarcón
Gilberto
G
D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D002675:Child, Preschool; D005260:Female; D020022:Genetic Predisposition to Disease; D006351:Heart Valves / Q000473:pathology; D006801:Humans; D008297:Male; D008800:Mexico; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic; D012214:Rheumatic Heart Disease / Q000235:genetics*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
D014409:Tumor Necrosis Factor-alpha