Objective: The objective of this study was to investigate the possible relationship between the TGF-beta1 gene C-509T and T869C polymorphisms and rheumatic heart disease (RHD), as well as their clinical significance.
Methods: Seventy-three patients with RHD diagnosed by echocardiography (mean age 31.7 +/- 14.7 y, male: female ratio 20:53) and, fifty-five age and sex-matched unrelated healthy volunteers (normal control) were included. Patients were classified according to age into children (n=24, mean age 14.4 +/- 3.1 y, and adults (n=49, mean age 40.2 +/- 9.9 y). TGF-beta genomic DNA was extracted and amplified using primers specific for C-509T and,T869C polymorphisms. Genotyping was performed by restriction fragment length polymorphism analysis (RFLP).
Results: T869C TT genotype was found significantly more frequently in RHD (total population) (OR: 3.27; [95% CI: 1.13-9.46]; P = 0.02), in children (OR: 6.0; [95% CI: 1.74-20.65]; P = 0.002) and in patients with combined valvular disease (CVD) (OR: 4.06; [95% CI: 1.32-12.48]; P = 0.01) compared to control subjects. 869T allele frequency was significantly higher in adults (OR: 1.89; [95% CI: 1.07-3.33]; P = 0.02), children (OR: 2.32; [95% CI: 1.16-4.66]; P = 0.0 1) and the total population (OR: 2.02; [95% CI: 1.21-3.39]; P = 0.006). C-509T genotypes distributions were not different between RHD patients and control subjects. However, -509T allele seems to confer susceptibility to RHD (OR: 1.78; [95% CI: 1.02-3.11]; P = 0.04). Both adults and children showed no significant difference in the genotypes distribution and allelic frequencies of TGF-beta1 C-509T polymorphism. In addition, genotype distribution and allelic frequencies of C-509T or T869C did not have any relation with the severity of the valvular affection.
Conclusion: TGF-beta1 T869C TT genotype, 869T allele and 509T allele are possible risk factor for RHD in Egypt. Future studies on larger populations are warranted.