RESUMEN
Apolipoprotein E (APOE) is recognized for its importance in lipoprotein metabolism and cardiovascular disease. We evaluated the association between APOE rs4420638 genotypes and circulating lipid concentrations along with the risk of coronary heart disease (CHD). We conducted a case-control study involving 1508 individuals to investigate the contribution of rs4420638 to the risk of CHD in Han Chinese. In addition, we performed a meta-analysis to evaluate the association between rs4420638 and CHD in Europeans and Asians. The results show that rs4420638 is significantly correlated with increased CHD risk in male Han Chinese [P = 0.040, odds ratio (OR) = 1.34, 95% confidential interval (95%CI) = 1.01-1.78] and is likely to increase the risk of CHD under the dominant model in males (P = 0.036, OR = 1.38, 95%CI = 1.02-1.88). A further subgroup analysis by rs4420638 genotype found a significant association of rs4420638 AA with high-density lipoprotein cholesterol (HDL-C) (P = 0.012) and APOA-I levels (P = 0.0001) in males. The meta-analysis suggests that rs4420638 significantly increases the risk of CHD (OR = 1.18, 95%CI = 1.14-1.22, P < 0.0001, fixed-effect method). Our case-control study shows that rs4420638 genotype AA has a significant association with the concentrations of circulating HDL-C and APOA-I in CHD in Han Chinese males. The meta-analysis suggests that rs4420638 is associated with CHD risk in Europeans and Asians.
Asunto(s)
Apolipoproteína A-I/sangre , Apolipoproteínas E/genética , HDL-Colesterol/sangre , Enfermedad de la Arteria Coronaria/sangre , Enfermedad de la Arteria Coronaria/genética , Polimorfismo Genético/genética , Anciano , Estudios de Casos y Controles , Humanos , Masculino , Persona de Mediana EdadRESUMEN
Coronary heart disease (CHD) has become a leading cause of human deaths worldwide. Recent studied showed that polymorphisms of the matrix metalloproteinase (MMP) genes played important roles in extracellular matrix remodeling and contribute to the pathogenesis of vascular diseases. Here, we investigated whether these MMP gene polymorphisms were associated with CHD in Han Chinese. Our case-control study was involved with 1509 unrelated individuals, including 777 CHD cases and 732 controls. We selected a total of five polymorphisms whose genotypes were determined using Sequenom iPLEX technology. Our results showed there were no significant associations between the five MMP gene polymorphisms and CHD risk at either genotype or allele levels (P > 0.05). Further subgroup analyses by sex were also unable to reveal any significant association (P > 0.05). In conclusion, no significant associations were found between the five MMP gene polymorphisms and the risk of CHD in Han Chinese.
Asunto(s)
Enfermedad de la Arteria Coronaria/enzimología , Enfermedad de la Arteria Coronaria/genética , Metaloproteinasas de la Matriz/genética , Polimorfismo de Nucleótido Simple/genética , Pueblo Asiatico/genética , Estudios de Casos y Controles , Predisposición Genética a la Enfermedad/genética , Genotipo , Humanos , Metaloproteinasa 1 de la Matriz/genética , Metaloproteinasa 12 de la Matriz/genética , Metaloproteinasa 13 de la Matriz/genética , Metaloproteinasa 2 de la Matriz/genética , Metaloproteinasa 9 de la Matriz/genéticaRESUMEN
APC is a tumor suppressor gene that is involved in the processes of cell migration and adhesion, transcriptional activation, and apoptosis. The goal of this study was to evaluate the contribution of the APC rs383830 polymorphism to coronary heart disease (CHD) in Han Chinese. A total of 783 patients with CHD and 737 controls were tested in the current association study. Although our study did not identify an association between the APC rs383830 polymorphism and CHD, a breakdown analysis by gender indicated there was a significant contribution of the rs383830 T allele to the risk of CHD in males (P = 0.046, odds ratio = 1.267, 95% confidence interval = 1.004-1.598). In conclusion, our study suggested a male-specific association of the APC rs383830 polymorphism with CHD.
Asunto(s)
Proteína de la Poliposis Adenomatosa del Colon/genética , Alelos , Enfermedad Coronaria/genética , Predisposición Genética a la Enfermedad , Polimorfismo de Nucleótido Simple , Anciano , Pueblo Asiatico , Estudios de Casos y Controles , Enfermedad Coronaria/etnología , Enfermedad Coronaria/patología , Femenino , Expresión Génica , Frecuencia de los Genes , Estudio de Asociación del Genoma Completo , Humanos , Masculino , Persona de Mediana Edad , Oportunidad Relativa , Factores de Riesgo , Factores SexualesRESUMEN
PPARD encodes peroxisome proliferator-activated re-ceptor delta, which has been shown to play an important role in control-ling lipid metabolism and atherosclerosis. In this case-control study, we explored the relationship between PPARD rs2016520 polymorphism and coronary heart disease (CHD) in a Han Chinese population. A to-tal of 657 CHD cases and 640 controls were included in the associa-tion study. rs2016520 polymorphism genotyping was performed using the melting temperature-shift polymerase chain reaction method. The PPARD rs2016520-G allele reduced CHD risk by 17.9% (χ(2) = 5.061, P = 0.025, OR = 0.821, 95%CI = 0.692-0.975). Furthermore, a signifi-cant difference in CHD risk was observed for the PPARD rs2016520 polymorphism in the dominant model (AG + GG vs AA: χ(2) = 4.751, degrees of freedom (df) = 1, P = 0.029, OR = 0.784, 95%CI = 0.631- 0.976). Analysis by age suggested that the G-allele decreased CHD risk by 14.8% in ages greater than 65 years (χ(2) = 4.446, P = 0.035, OR = 0.852, 95%CI = 0.684-1.060). In contrast, meta-analysis of PPARD rs2016520 among 3732 cases and 5042 controls revealed no associa-tion between PPARD rs2016520 and CHD (P = 0.19). We found that the PPARD rs2016520-GG genotype decreased CHD risk in a Han Chinese population. Moreover, we found an association between serum high-density lipoprotein cholesterol level and PPARD rs2016520 in senior individuals aged ≥ 65 years. The meta-analysis revealed no association between PPARD rs2016520 and CHD, suggesting ethnic differences in the association between the PPARD locus and CHD.
Asunto(s)
Enfermedad de la Arteria Coronaria/genética , Estudios de Asociación Genética , Predisposición Genética a la Enfermedad , PPAR delta/genética , Anciano , Anciano de 80 o más Años , Pueblo Asiatico/genética , Enfermedad de la Arteria Coronaria/patología , Femenino , Genotipo , Humanos , Metabolismo de los Lípidos/genética , Masculino , Polimorfismo de Nucleótido Simple/genéticaRESUMEN
Recently, the nested genes G72 and G30 on chromosome 13q32-q33 have been implicated in the etiology of schizophrenia. We genotyped six single-nucleotide polymorphisms (SNPs: rs3916965, rs3916967, rs2391191, rs778294, rs779293 and rs3918342), which span approximately 82.5 kb in the region encompassing the G72/G30 genes in 1176 Han Chinese subjects (588 cases and 588 controls) and 365 Scottish subjects (183 cases and 182 controls). Significant association between an allele of marker rs778293 and schizophrenia was found in our Chinese samples (P = 0.0013), and was replicated in the Scottish samples (P = 0.022). LD analysis revealed that four SNPs between rs3916965 and rs778294 were in LD, called block I, and the two distal SNPs (rs778293 and rs3918342) constituted a block II in both the Chinese and Scottish samples. We selected one SNP from each block (rs778294 from block I and rs778293 from block II), and then analyzed the haplotypes. A significant difference was observed for the common haplotype GC in the Chinese sample (P = 0.0145), and was replicated in the Scottish sample (P = 0.003). On meta-analysis, we separately analyzed the studies in Asian and European populations because of significant heterogeneity in the homogeneity test. We found a statistically significant association between rs778293 and schizophrenia in Asian populations, but no difference was found between cases and controls in the European populations. Overall, our data give further support to the existing evidence that G72/G30 genes are involved in conferring susceptibility to schizophrenia.
Asunto(s)
Proteínas Portadoras/genética , Cromosomas Humanos Par 13/genética , Predisposición Genética a la Enfermedad , Proteínas/genética , Esquizofrenia/etnología , Esquizofrenia/genética , Adulto , Pueblo Asiatico/genética , Estudios de Casos y Controles , China , Femenino , Frecuencia de los Genes , Haplotipos/genética , Humanos , Péptidos y Proteínas de Señalización Intracelular , Desequilibrio de Ligamiento , Masculino , Linaje , Polimorfismo de Nucleótido Simple/genética , ARN Mensajero , Valores de Referencia , Escocia , Población Blanca/genéticaRESUMEN
BACKGROUND: Iodine deficiency is the commonest cause of preventable mental retardation (MR) worldwide. However, in iodine-deficient areas not everyone is affected and familial aggregation is common. This suggests that genetic factors may also contribute. Thyroid hormone (TH) plays an important role in fetal and early postnatal brain development. The pro-hormone T4 (3,3',5,5'-triiodothyronine) is converted in the brain to its active form, T3, or its inactive metabolite, reverse T3, mainly by the action of deiodinase type 2 (DIO2). METHODS: To investigate the potential genetic contribution of the DIO2 gene, we performed a case-control association study using three common SNPs in the gene (rs225014, rs225012, and rs225010) that were in strong linkage disequilibrium with each other. RESULTS: Single marker analysis showed a positive association of MR with rs225012 and rs225010. Particularly with rs255012 [corrected], CC [corrected] genotype frequency was significantly higher in MR cases than in controls (chi squared [corrected] = 9.18, p = 0.00246). When we compared the distributions of common haplotypes, we also found significant differences between mental retardation and controls in the haplotype combination of rs225012 and rs225010 (chi2 = 15.04, df 2, global p = 0.000549). This association remained significant after Bonferroni correction (p = 0.0016470). CONCLUSION: We conclude that allelic variation in the DIO2 gene may affect the amount of T3 available and in an iodine-deficient environment may partly determine overall risk of MR.
Asunto(s)
Discapacidad Intelectual/genética , Yoduro Peroxidasa/genética , Yodo/deficiencia , Adolescente , Niño , Preescolar , China/epidemiología , Femenino , Marcadores Genéticos/genética , Haplotipos/genética , Humanos , Discapacidad Intelectual/enzimología , Yodo/metabolismo , Desequilibrio de Ligamiento/genética , Masculino , Polimorfismo de Nucleótido Simple/genética , Triyodotironina/metabolismo , Yodotironina Deyodinasa Tipo IIRESUMEN
BACKGROUND: The gene for insulin-degrading enzyme (IDE) represents a strong positional and biologic candidate for late-onset Alzheimer disease (LOAD) susceptibility. IDE is located on chromosome 10q23.3 close to a region of linkage for LOAD. In addition, many studies have identified a possible role of IDE in the degradation of amyloid beta-protein and the intracellular amyloid precursor protein (APP) domain released by gamma-secretase processing. OBJECTIVE: To examine the association of IDE with AD in the Han Chinese. METHODS: Four IDE polymorphisms (three in 5'-untranslated region and one in intron 21) were analyzed, using a population of 210 patients with LOAD and 200 control subjects well matched for age, sex, and ethnic background. RESULTS: Among the four polymorphisms studied, only the C allele of single-nucleotide polymorphism (SNP) IDE2 showed association with AD (p = 0.005). Stratification of the data by APOE epsilon4 status indicated that the association between IDE2 and AD was confined to APOE epsilon4 carriers only. No association was found between all variants studied and AD within APOE epsilon4-negative subjects. The global haplotype frequencies showed significant differences between AD patients and control subjects. Furthermore, overrepresentation of GCTG haplotype in the AD group was found. It may be a risk haplotype for AD. CONCLUSIONS: These results suggest a possible synergic interaction between IDE and APOE epsilon4 in the risk to develop late-onset sporadic AD. IDE might modify the effect of the APOE epsilon4 risk factor in the Han Chinese population.
