RESUMEN
Rheumatic heart disease (RHD) is one of the most severe consequences of rheumatic fever. It has been suggested that angiotensin I-converting enzyme (ACE) may be involved in the increased valvular fibrosis and calcification in the pathogenesis of RHD. We conducted a case-control study to look for association of ACE I/D polymorphism with RHD in Indian population. The study incorporated 300 patients (170 males and 130 females) with RHD, and 200 controls (118 males and 82 females). We also subgrouped RHD patients into mitral valve lesion (MVL) and combined valve lesion (CVL). ACE I/D polymorphism was identified using polymerase chain reaction method. We also performed a meta-analysis of three published studies and the present study (636 RHD cases and 533 controls) to evaluate the association between the ACE I/D polymorphisms and RHD risk. A significant difference in ACE ID and DD genotypes distribution between RHD cases (OR = 1.62, 95% CI = 1.11-2.36 and OR = 2.08, 95% CI = 1.02-4.15, respectively) and corresponding controls was observed. On comparing the ACE genotypes of MVL and CVL subgroups with controls, ID and DD genotypes were also significantly associated with CVL (FDR Pcorr = 0.009, OR = 2.19 and FDR Pcorr = 0.014, OR = 3.29, respectively). Meta-analysis also suggested association of the ACE D allele (FDR Pcorr = 0.036, OR-1.22, 95% CI 1.02-1.45) with RHD. In conclusion, ACE ID and DD genotypes are associated with an increased risk of RHD, particularly CVL. This suggests that the ACE I/D gene polymorphism may play an important role in the pathogenesis of RHD.
Asunto(s)
Predisposición Genética a la Enfermedad , Mutación INDEL/genética , Peptidil-Dipeptidasa A/genética , Polimorfismo Genético , Cardiopatía Reumática/enzimología , Cardiopatía Reumática/genética , Adolescente , Adulto , Distribución por Edad , Estudios de Casos y Controles , Niño , Femenino , Frecuencia de los Genes , Enfermedades de las Válvulas Cardíacas/enzimología , Enfermedades de las Válvulas Cardíacas/genética , Humanos , India , Masculino , Persona de Mediana Edad , Adulto JovenRESUMEN
Dose requirements for oral anticoagulants in thromboembolic events are influenced by polymorphisms in VKORC1 and CYP2C9 genes. The Indian population comprises multiple ethnic groups but no data is available on allele frequencies of these genes for North Indians. The present study aimed at establishing the allele and genotype frequencies of VKORC1 -1639 G>A, CYP2C9*2 and CYP2C9*3 alleles in the North Indian population. One hundred and two healthy subjects from the Northern Indian region were genotyped for VKORC1 -1639 G>A, CYP2C9*2 and CYP2C9*3 by polymerase chain reaction and restriction fragment length polymorphism. Allele frequencies were compared with that of the HapMap populations. The allele frequencies for VKORC1 -1639 A, CYP2C9*2 and CYP2C9*3 were found to be 14.22%, 4.90% and 3.92% respectively. This report also describes the inter-ethnic differences in the Northern Indian frequencies of VKORC1 -1639 G>A, CYP2C9*2 and CYP2C9*3 alleles with that of other populations and HapMap project data. VKORC1 -1639 G>A allele is present at moderately high frequency in the Northern Indian population. The frequencies of CYP2C9*2 and CYP2C9*3 alleles are also found to be different from other populations.