RESUMO
INTRODUCTION: Thrombospondin 1 and 2 are multidomain calcium-binding extracellular glycoproteins and they play a role in platelet aggregation, inflammatory response and assembly of connective tissue extracellular matrix. The association of thrombospondins (TSP) in the pathogenesis of coronary artery disease (CAD) and myocardial infarction (MI) is well established. The association of the TSP-1 (Asn700Ser, 2210A â G, rs2228262) and TSP-2 un-translated region (UTR) (3949T â G, rs8089) gene variations among South Indian CAD and MI patients has been examined in the present study. MATERIALS AND METHODS: We analyzed the thrombospondin polymorphisms in unrelated CAD patients (n = 511) and a subgroup with an event of MI (n = 173) compared with controls (n = 522). The polymorphisms were assessed using polymerase chain reaction, restriction fragment length analysis and the circulating TSP concentration were measured using enzyme linked immune-sorbent assay. RESULTS: The prevalence of TSP-1 and TSP-2 alleles did not show any significant difference statistically, when compared controls against CAD/MI patients. The rare GG genotype of the N700S polymorphism was not observed among the studied population. Further, multiple regression analysis revealed that there was no significant risk for CAD (OR = 1.68; 95% CI 0.927 - 3.055; p = 0.087) or MI (OR = 1.84; 95% CI 0.846 - 4.007; p = 0.124) for the GA genotype. The GA genotype showed no impact on clinical characteristics of the CAD patients and their circulating TSP-1 levels. A similar non-association was observed for the TSP-2 in 3949T â G polymorphism (GG genotype) for CAD (OR = 0.64; 95% CI 0.278 - 1.455; p = 0.636) and MI (OR = 0.53; 95% CI 0.166 - 1.675; p = 0.278). CONCLUSIONS: Our data suggests that the presence of thrombospondin-1 (rs2228262) and thrombospondin-2 (rs8089) variants need not be considered a risk for coronary artery disease or myocardial infarction among South Indians.
Assuntos
Doença da Artéria Coronariana/etnologia , Doença da Artéria Coronariana/genética , Infarto do Miocárdio/etnologia , Infarto do Miocárdio/genética , Polimorfismo de Nucleotídeo Único , Trombospondina 1/genética , Trombospondinas/genética , Estudos de Casos e Controles , Distribuição de Qui-Quadrado , Doença da Artéria Coronariana/sangue , Ensaio de Imunoadsorção Enzimática , Feminino , Frequência do Gene , Estudos de Associação Genética , Predisposição Genética para Doença , Humanos , Índia/epidemiologia , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/sangue , Razão de Chances , Fenótipo , Reação em Cadeia da Polimerase , Medição de Risco , Fatores de Risco , Trombospondina 1/sangue , Trombospondinas/sangueRESUMO
BACKGROUND: An adverse pattern of blood lipids and atherosclerosis begin in childhood. Unfortunately, data for children and adolescents, particularly those in the Indian population, are scarce. The present study aims to evaluate the levels of serum E-selectin in Indian children and adolescents and its correlation with anthropometric and biochemical parameters. METHODS: The study groups included 338 school children and adolescents. There were 96 obese children, 97 overweight children and 42 children with congenital heart disease who were compared with 103 normal controls, aged 10-17 years. Serum E-selectin and serum leptin were analyzed with enzyme-linked immunosorbent assay kits. Lipid profile and fasting glucose were analyzed using an autoanalyzer. RESULTS: Serum E-selectin levels were significantly increased in obese (65.3 ± 8.39 ng/mL) and overweight (56.01 ± 6.96 ng/mL) subjects (P < 0.001). However, these levels were lower in children with congenital heart disease (40.99 ± 6.54 ng/mL) than in controls (43.79 ± 6.71 ng/mL). CONCLUSION: Serum E-selectin levels showed good positive association with body mass index, waist-to-hip ratio, systolic and diastolic blood pressure, leptin, total cholesterol, triglycerides and low-density lipoprotein cholesterol and showed negative correlation with fasting glucose and no significant association with high-density lipoprotein cholesterol. These findings indicate that higher E-selectin levels can induce endothelial activation and play an essential role in the earliest stage of the atherosclerotic process in obese and overweight children. Regular camps at schools to counsel the identified overweight and obese children and to encourage physical exercise would help to reduce the risk of these children being prone to major cardiovascular anomalies in adulthood.
Assuntos
Selectina E/sangue , Cardiopatias/sangue , Cardiopatias/congênito , Sobrepeso/sangue , Adolescente , Aterosclerose/sangue , Biomarcadores/sangue , Glicemia/análise , Pressão Sanguínea , Índice de Massa Corporal , Criança , Colesterol/sangue , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Índia , Leptina/sangue , Masculino , Obesidade/sangue , Triglicerídeos/sangueRESUMO
The chromosomal region 9p21 has been reported to be associated with myocardial infarction, coronary artery disease (CAD), diabetes, and many other related multifactorial diseases in humans. Although the genome-wide association studies have identified a limited number of single-nucleotide polymorphisms (SNPs) at 9p21 for CAD risk, the role of flanking SNPs has not been studied so far. Therefore, in the present work, we studied the role of flanking SNPs with respect to that of the previously identified SNPs rs10757278 and rs2383207 at 9p21 among the Indian subjects found to have CAD (n = 414) along with age- and sex-matched control subjects (n = 408). Our study replicated the association of genome-wide association studies that had identified SNPs rs2383207 (p = 4.7 × 10(-5)) and rs10757278 (p = 5.5 × 10(-5)) among Indians with CAD. Further, we evaluated nine additional SNPs, of which two SNPs flanking rs2383207 (rs1537375 [p = 2.4 × 10(-5)] and rs1537374 [p = 5.6 × 10(-5)]) were also strongly associated with CAD. The haplotypes constructed using four risk SNPs revealed that the haplotypes with combinations of rs10757278 showed CAD risks, whereas the minor alleles of rs2383207, rs1537375, and rs1537374 in combinations reduce the CAD risks substantially. Our study demonstrates that the variation in the chromosomal region 9p21 is involved in modifying progression toward CAD among Indians and the risk may be variable, contributed by the SNPs that are flanking previously identified SNPs.
Assuntos
Cromossomos Humanos Par 9/genética , Doença da Artéria Coronariana/genética , Predisposição Genética para Doença/genética , Haplótipos/genética , População Branca/genética , Feminino , Frequência do Gene , Loci Gênicos/genética , Humanos , Índia/etnologia , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único/genéticaRESUMO
BACKGROUND AND AIMS: Peroxisome proliferator activated receptor-gamma (PPARgamma) and lipoprotein lipase (LPL) genes are important in pathways of triglyceride metabolism, insulin resistance and adipogenesis. We hypothesized that polymorphisms of PPARgamma Pro12Ala, LPL HindIII and LPL Ser447X influence severity of coronary artery disease (CAD) in an Indian population. METHODS: PPARgamma Pro12Ala, LPL HindIII and LPL Ser447X polymorphisms were genotyped in 414 patients with CAD and matched with 424 controls. The study subjects were inducted after standard diagnostic procedures and analyzed statistically for the association of polymorphisms with clinical characteristics. RESULTS: We found that PPARgamma alleles were not associated with CAD among Indians although proline carriers had significantly higher levels of HDL-cholesterol (p = 0.03) among CAD patients. The LPL HindIII also had no significant correlations for CAD or for any clinical characteristics. The Ser447X polymorphism (p = 0.015) influenced lower triglyceride levels among CAD patients with significant associations (OR = 0.66, 95% CI 0.483-0.915, p = 0.012). This protective effect of the 447X allele was more pronounced among the CAD patients without the risk factor of diabetes (OR = 0.60, 95% CI 0.403-0.907, p = 0.014) along with less progression of a severe atherosclerotic disease. CONCLUSIONS: PPARgamma and LPL have intractable roles in pathways that lead to CAD, but their gene polymorphisms associate differently. Our results imply a significant correlation of Ser447X polymorphism and its protective effect on Indians against severity of CAD modified by the risk of diabetes, than LPL HindIII and PPARgamma Pro12Ala.
Assuntos
Doença da Artéria Coronariana/genética , Lipase Lipoproteica/genética , PPAR gama/genética , Sequência de Bases , Estudos de Casos e Controles , Primers do DNA , Feminino , Humanos , Índia , Masculino , Pessoa de Meia-IdadeRESUMO
Apolipoprotein C3 and apolipoprotien A5 are proteins coded from the APOA1/C3/A4/A5 gene cluster. Sst I polymorphism on apolipoprotein C3 and -1131C polymorphism of apolipoprotien A5 are key variants involved in triglyceride metabolism and cause a significant cardio-metabolic risk. Here, we have evaluated these two variants for their roles in coronary artery disease in patients of the Indian population. The apolipoprotein gene cluster variants were analysed in 416 angiographically determined coronary artery disease patients and matched 416 controls using polymerase chain reaction-restriction fragment length polymorphism. The characteristics of the study subjects were analyzed statistically for their association with the polymorphisms. The alleles were combined as haplotypes and their combined risks were evaluated. The minor allele genotypes of both apolipoprotein C3 (S2) and apolipoprotien A5 (C) had a significant risk for coronary artery disease. The S2 allele genotyped patients had a significantly increased triglyceride level (P < 0.001) and increased triglycerides were observed among both patient and control CC genotype carriers. We identified the haplotype S2/C with a significant increased risk (P < 0.001) to coronary artery disease with increased levels of circulating triglycerides compared to other haplotypes in patients. We conclude that the variants on apolipoprotein C3 and apolipoprotien A5 modulate serum triglyceride levels and increase the risk of coronary artery disease.