RESUMO
The aim of the present study was to evaluate the role of AGT and REN gene polymorphisms as susceptibility markers for coronary artery disease (CAD) and/or restenosis after coronary stent placement in a group of Mexican patients. Five polymorphisms of the AGT (rs699, rs4762, rs5051, rs5049, rs5046) and two of the REN (rs5707, rs5705) genes were analyzed by 5' exonuclease TaqMan genotyping assays in 240 patients with CAD who underwent coronary artery stenting (76 with restenosis and 164 without restenosis). A group of 610 individuals without clinical and familial antecedents of cardiovascular diseases were included as controls. The results showed that the distribution of AGT and REN polymorphisms were similar in patients with and without restenosis. However, when the whole group of patients (with and without restenosis) was compared to healthy controls, under co-dominant, dominant, heterozygous and additive models, the REN A4280C (rs5705) polymorphism was associated with increased risk of CAD (OR=1.76, PCo-dom=0.006, OR=1.81, PDom=0.001, OR=1.75, PHet=0.003 and OR=1.59, PAdd=0.003, respectively). All models were adjusted for age, gender, diabetes, dyslipidemia, hypertension and smoking habit. The TC haplotype of the REN gene was associated with increased risk of CAD (OR=1.53, P=0.014). The data suggest that the REN C4280A (rs5705) polymorphism plays an important role in the risk of developing CAD with the highest risk for C allele, but do not support its role as a risk factor for developing restenosis after coronary stenting.
Assuntos
Doença da Artéria Coronariana/genética , Polimorfismo de Nucleotídeo Único , Renina/genética , Idoso , Alelos , Angiotensinogênio/genética , Angiotensinogênio/metabolismo , Estudos de Casos e Controles , Biologia Computacional , Reestenose Coronária/genética , Feminino , Frequência do Gene , Marcadores Genéticos , Predisposição Genética para Doença , Técnicas de Genotipagem , Haplótipos , Heterozigoto , Humanos , Desequilíbrio de Ligação , Modelos Logísticos , Masculino , México , Pessoa de Meia-Idade , Renina/metabolismo , Fatores de Risco , StentsRESUMO
The aim of the present study was to establish the role of IL-6 and TGF-ß1 gene polymorphisms in the risk of developing in-stent restenosis. Two IL-6 [rs1800796 (-572 G>C), rs2069827 (-1426 T>G)] and two TGF-ß1 [rs1800469 (-509 T>C), rs1800470 (T29C)] gene polymorphisms were analyzed by 5' exonuclease TaqMan genotyping assays in a group of 244 patients, who underwent coronary artery stenting. Basal and procedure coronary angiography were analyzed, looking for angiographic predictors of restenosis and follow-up angiography was performed to screen for binary restenosis. Under the dominant and additive models adjusted for hypertension, stable angina, stent used, and diameter of stent, the TGF-ß1 T29C (rs1800470) polymorphism was significantly associated with an increase risk of restenosis when compared to patients without restenosis (OR=2.06, 95% CI: 1.03-4.11, P(Dom)=0.034 and OR=1.64, 95% CI: 1.09-2.45, PAdd=0.016). TGF-ß1 polymorphisms were in linkage disequilibrium and one haplotype (TT) was significantly increased in patients with restenosis when compared to patients without restenosis (OR=2.03, P=0.041). In summary, our results suggest that the TGF-ß1 T29C gene polymorphism could be involved in the risk of developing restenosis after coronary stent placement.
Assuntos
Biomarcadores/metabolismo , Doença da Artéria Coronariana/cirurgia , Reestenose Coronária/genética , Interleucina-6/genética , Polimorfismo Genético/genética , Complicações Pós-Operatórias , Stents , Fator de Crescimento Transformador beta1/genética , Idoso , Angiografia Coronária , Reestenose Coronária/metabolismo , Reestenose Coronária/patologia , Feminino , Seguimentos , Predisposição Genética para Doença , Genótipo , Humanos , Masculino , México , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , PrognósticoRESUMO
The aim of the present study was to establish the role of HIF1A gene polymorphisms in the risk of developing premature coronary artery disease (CAD) in a well-characterized clinical cohort. Three polymorphisms in HIF1A (rs11549465, rs11549467, rs2057482) gene were genotyped in 949 patients with premature CAD, and 676 healthy controls (with negative calcium score by computed tomography). Under a dominant model adjusted for age, visceral to subcutaneous adipose tissue (VAT/SAT) ratio, hypertension, type 2 diabetes mellitus (T2DM), HDL-C levels, hypercholesterolemia and hypertriglyceridemia, the rs2057482 T allele was associated with decreased risk of premature CAD when compared to healthy controls (OR = 0.616, P(dom) = 0.020). The effect of the studied polymorphisms on various metabolic parameters and cardiovascular risk factors was explored. In this analysis, the rs2057482 T allele was associated with decreased risk of obesity, central obesity, hypertension, hypercholesterolemia, hypertriglyceridemia and increased risk of T2DM. Under a dominant model adjusted by age, the HIF1A rs2057482 T polymorphism was associated with high VAT/SAT ratio (P = 0.009) and HDL-C levels (P = 0.04) in healthy controls. The results suggest that HIF1A rs2057482 polymorphism is involved in the risk of developing CAD and is associated with some metabolic parameters and cardiovascular risk factors.
Assuntos
Doença da Artéria Coronariana/genética , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Polimorfismo de Nucleotídeo Único , Adulto , Alelos , Estudos de Casos e Controles , HDL-Colesterol/sangue , LDL-Colesterol/sangue , Estudos de Coortes , Feminino , Frequência do Gene , Predisposição Genética para Doença , Haplótipos , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Gordura Intra-Abdominal/metabolismo , Modelos Logísticos , Masculino , México , Pessoa de Meia-Idade , Fatores de Risco , Gordura Subcutânea Abdominal/metabolismoRESUMO
The aim of the present study was to establish the role of ACE gene polymorphisms in the risk of developing in-stent restenosis and/or coronary artery disease (CAD). Eight ACE gene polymorphisms were genotyped by 5' exonuclease TaqMan genotyping assays in 236 patients with CAD who underwent coronary artery stenting. Basal and procedure coronary angiographies were analyzed searching for angiographic predictors of restenosis and follow-up angiography was analyzed looking for binary restenosis. A group of 455 individuals without clinical and familial antecedents of cardiovascular diseases were included as controls. Haplotypes were constructed after linkage disequilibrium analysis. Distribution of ACE polymorphisms was similar in patients with and without restenosis. Similar results were observed when the analysis was made comparing the whole group of patients (with and without restenosis) and healthy controls. Six out of eight polymorphisms were in high linkage disequilibrium and were included in five haplotypes (AAAGCA, GGGATG, GAGATG, AGAGCA and AAGACA). The distribution of these haplotypes was similar in patients with and without restenosis. However, CAD patients showed an increased frequency of the AAAGCA haplotype (OR=1.31, 95% CI: 1.04-1.66, P=0.018) and decreased frequencies of GAGATG (OR=0.47, 95% CI: 0.25-0.88, P=0.011) and AGAGCA (OR=0.15, 95% CI: 0.02-0.65, P=0.002) haplotypes when compared to healthy controls. Haplotypes of the ACE gene could be a genetic factor related to coronary artery disease in the Mexican individuals, but do not support its role as a risk factor for developing restenosis after coronary stenting.
Assuntos
Doença da Artéria Coronariana/genética , Reestenose Coronária/genética , Haplótipos , Peptidil Dipeptidase A/genética , Idoso , Reestenose Coronária/etiologia , Feminino , Seguimentos , Frequência do Gene , Predisposição Genética para Doença , Humanos , Desequilíbrio de Ligação , Masculino , México , Pessoa de Meia-Idade , Polimorfismo Genético , Polimorfismo de Nucleotídeo Único , StentsRESUMO
Interleukin 15 (IL-15) is a Th1-related cytokine that triggers inflammatory cell recruitment with implications for pathogenesis in ulcerative colitis. The IL-15 gene is located within a 35 kb region of the q28-31 locus of chromosome 4. In the present work, the role of IL-15 gene polymorphisms as susceptibility markers for UC was evaluated. Seven polymorphisms of IL-15 (rs3806798, rs10833, rs4956403, rs2254514, rs2857261, rs10519613, and rs1057972) were genotyped by 5' exonuclease TaqMan genotyping assays in a group of 199 Mexican patients with UC and 698 Mexican Mestizo healthy unrelated individuals. UC patients and healthy controls showed similar distribution of the rs3806798, rs10833, rs4956403, rs2857261, rs10519613, and rs1057972 polymorphisms. The rs2254514 polymorphism was significantly associated with decreased risk of UC as compared to controls under both dominant and additive models (OR 0.62, Pdom = 0.014 and OR 0.65, Padd = 0.02). The rs2254514 CC genotype was associated with young age at diagnosis <40 years (P = 0.03; OR 3.67). Five polymorphisms (rs1051613, rs2254514, rs2857261, rs1057972, and rs10833) were in strong linkage disequilibrium and were included in six haplotypes: H1 (ACAAC), H2 (CCGTC), H3 (CTAAT), H4 (CCAAT), H5 (CTAAC), and H6 (CCAAC). UC patients showed an increased frequency of the H6 haplotype (P = 0.005; OR 3.2) and a decreased frequency of the H5 haplotype (P = 0.031; OR 0.40). These results suggest that the IL-15 rs2254514 polymorphism might have an important role in the development of UC in the Mexican population. We were able to distinguish one risk and one protective uncommon haplotype for the development of UC.
Assuntos
Colite Ulcerativa/genética , Predisposição Genética para Doença , Interleucina-15/genética , Polimorfismo de Nucleotídeo Único , Adulto , Idoso , Alelos , Estudos de Casos e Controles , Colite Ulcerativa/diagnóstico , Colite Ulcerativa/tratamento farmacológico , Feminino , Frequência do Gene , Estudos de Associação Genética , Haplótipos , Humanos , Desequilíbrio de Ligação , Masculino , México , Pessoa de Meia-Idade , Razão de Chances , Risco , Adulto JovemRESUMO
Inflammation plays an essential role in the development and progression of atherosclerotic lesions, and plaque disruption. The TGF-ß1 plays an important role in the anti-inflammatory process. The aim of the present study was to evaluate the role of TGF-ß1 gene polymorphisms as susceptibility markers for acute coronary syndrome (ACS). Two polymorphisms (TGF-ß -509T>C and TGF-ß T29C) of the TGF-ß gene were analyzed by 5' exonuclease TaqMan genotyping assays in a group of 426 patients with coronary acute syndrome and 551 healthy unrelated controls. A significant difference was observed in the distribution of TGF-ß T29C polymorphism between ACS patients and healthy controls (P<10(-3)). According to the co-dominant model, individuals with the TGF-ß 29 TT genotype have a 2.5-fold increased risk of developing ACS (P<10(-3)). Multiple logistic analysis showed that the largest risk factor for developing ACS was given by smoking habit, diabetes, hypertension, dyslipidemia, and the TGF-ß1 29 TT genotype. The analysis of linkage disequilibrium showed one haplotype (TT) with increased frequency and one haplotype (CC) with decreased frequency in ACS patients when compared to healthy controls. The results suggest that TGF-ß1 T29C gene polymorphism could be involved in the risk of developing ACS in Mexican individuals.
Assuntos
Síndrome Coronariana Aguda/genética , Predisposição Genética para Doença , Polimorfismo Genético , Fator de Crescimento Transformador beta1/genética , Idoso , Alelos , Estudos de Casos e Controles , Feminino , Humanos , Masculino , México , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase Via Transcriptase ReversaRESUMO
BACKGROUND: A consistent line of investigation suggests that autonomic nervous system dysfunction may explain the multi-system features of fibromyalgia (FM); and that FM is a sympathetically maintained neuropathic pain syndrome. Dorsal root ganglia (DRG) are key sympathetic-nociceptive short-circuit sites. Sodium channels located in DRG (particularly Nav1.7) act as molecular gatekeepers for pain detection. Nav1.7 is encoded in gene SCN9A of chromosome 2q24.3 and is predominantly expressed in the DRG pain-sensing neurons and sympathetic ganglia neurons. Several SCN9A sodium channelopathies have been recognized as the cause of rare painful dysautonomic syndromes such as paroxysmal extreme pain disorder and primary erythromelalgia. The aim of this study was to search for an association between fibromyalgia and several SCN9A sodium channels gene polymorphisms. METHODS: We studied 73 Mexican women suffering from FM and 48 age-matched women who considered themselves healthy. All participants filled out the Fibromyalgia Impact Questionnaire (FIQ). Genomic DNA from whole blood containing EDTA was extracted by standard techniques. The following SCN9A single-nucleotide polymorphisms (SNP) were determined by 5' exonuclease TaqMan assays: rs4371369; rs4387806; rs4453709; rs4597545; rs6746030; rs6754031; rs7607967; rs12620053; rs12994338; and rs13017637. RESULTS: The frequency of the rs6754031 polymorphism was significantly different in both groups (P = 0.036) mostly due to an absence of the GG genotype in controls. Interestingly; patients with this rs6754031 GG genotype had higher FIQ scores (median = 80; percentile 25/75 = 69/88) than patients with the GT genotype (median = 63; percentile 25/75 = 58/73; P = 0.002) and the TT genotype (median = 71; percentile 25/75 = 64/77; P = 0.001). CONCLUSION: In this ethnic group; a disabling form of FM is associated to a particular SCN9A sodium channel gene variant. These preliminary results raise the possibility that some patients with severe FM may have a dorsal root ganglia sodium channelopathy.
Assuntos
Fibromialgia/genética , Gânglios Espinais/patologia , Polimorfismo Genético/genética , Índice de Gravidade de Doença , Canais de Sódio/genética , Adulto , Estudos de Casos e Controles , Feminino , Fibromialgia/epidemiologia , Fibromialgia/etnologia , Predisposição Genética para Doença/etnologia , Predisposição Genética para Doença/genética , Genótipo , Humanos , México/epidemiologia , Pessoa de Meia-Idade , Canal de Sódio Disparado por Voltagem NAV1.7 , Nociceptores/patologiaRESUMO
Inflammation plays an important role in the pathogenesis of atherosclerosis and acute coronary syndromes (ACS). Interleukin-10 (IL-10) is a potent anti-inflammatory cytokine that mediates the inflammatory process. The objective of the present study was to evaluate the role of IL-10 gene polymorphisms as susceptibility markers for ACS in Mexican patients. IL-10 promoter polymorphisms (positions -1082, -819, and -592) were analyzed by 5' exonuclease TaqMan genotyping assays in 389 ACS patients and 302 healthy controls. ACS patients showed increased frequencies of IL-10-592 C allele and CC genotype when compared to healthy controls (pC=0.0006, OR=1.48 and pC=0.022, OR=1.56, respectively), whereas the frequencies of the A allele and AA genotype were decreased in patients (pC=0.0006, OR=0.68 and pC=0.006, OR=0.57, respectively). When the distribution of IL-10-592 genotypes was analyzed separately in women and men (patients and healthy controls), a different distribution of alleles and genotypes was observed only in the group of men. In this case, increased frequency of C allele (pC=0.004, OR=1.46) and decreased frequencies of A allele (pC=0.004, OR=0.68) and AA genotype (pC=0.023, OR=0.56) were observed in the group of patients when compared to healthy controls. Multiple logistic analyses by gender showed that male individuals with IL-10-592CC+AC genotypes had 3.54-fold increased risk of developing ACS than individuals with AA genotype (p<0.001). The analysis of linkage disequilibrium showed one (ACC) increased haplotype in patients as compared to healthy controls. The results suggest that IL-10 gene polymorphisms could be involved in the risk of developing ACS in the Mexican population.
Assuntos
Síndrome Coronariana Aguda/genética , Alelos , Predisposição Genética para Doença , Haplótipos/genética , Interleucina-10/genética , Polimorfismo de Nucleotídeo Único/genética , Idoso , Estudos de Casos e Controles , Feminino , Frequência do Gene/genética , Humanos , Masculino , México , Pessoa de Meia-Idade , Fatores de RiscoRESUMO
Takayasu's arteritis (TA) and tuberculosis (TB) have been associated with major histocompatibility complex genes, especially HLA-B alleles. However, different HLA-B alleles have been detected in these diseases. The aim of the study was to compare the distribution of the residues 63 and 67 on the HLA-B molecule in patients with TA and TB in order to establish a genetic relationship between these two diseases. HLA-B sequences obtained in 30 patients with TB were compared to those previously reported in TA and healthy controls. 8 out of 30 TB patients studied (26.6%) presented at least one allele with glutamic acid at position 63 and serine at position 67. This was observed in 73% of the TA patients (p = 0.0005). Ten TB (10/30 = 33.3%) and two TA patients (2/26 = 7.7%) did not show similarity at the mentioned positions (p = 0.019). This preliminary study suggests a difference in the distribution of the residues 63 and 67 of the HLA-B alleles in patients with TA and TB.
Assuntos
Aminoácidos/genética , Antígenos HLA-B/genética , Arterite de Takayasu/genética , Tuberculose/genética , HumanosRESUMO
A possible relationship between Takayasu arteritis (TA) and Tuberculosis (Tb) has been suggested. Both diseases present similar chronic inflammatory lesions and occasionally granulomas on the arterial walls. The genetic relationship between these two diseases has not been explored before, however, both diseases have been associated with human leukocyte antigen (HLA) alleles. Therefore, the aim of the present study was to analyze the distribution of HLA-B alleles in TA (n = 40) and Tb (n = 34) patients and healthy controls (72 exposed and 99 nonexposed). HLA-B alleles were determined by reverse dot blot. The statistical methods used included the Chi(2), and odds ratio (OR) with 95% confidence intervals. In spite of the loose clinical relationship between TA and Tb, we did not detected any genetic relationship between them when the HLA-B alleles were analyzed in these groups of patients. On the contrary, we detected distinct specific HLA-B alleles for each disease. TA was characterized by HLA-B39, -B44, and -B52, pulmonary Tb by HL-B35 and extrapulmonary Tb by HLA-B39 and -B40. This preliminary study suggests a difference in the distribution of HLA-B alleles in patients with TA and Tb.
Assuntos
Frequência do Gene , Antígenos HLA-B/genética , Arterite de Takayasu/genética , Tuberculose/genética , Adolescente , Adulto , Criança , Feminino , Homozigoto , Humanos , Masculino , México , Pessoa de Meia-Idade , Análise Multivariada , Razão de Chances , Tuberculose Pulmonar/genéticaRESUMO
The secretory phospholipase A2 II A (sPLA2-IIA) encoded by PLA2G2A gene hydrolyzes phospholipids liberating free fatty acids (FFAs) and lysophospholipids. If lipolysis exceeds lipogenesis, the free fatty acids undergo a continuous release into circulation. A sustained excessive increase in this release contributes to metabolic disease. The aim of the present study was to evaluate the role of PLA2G2A gene polymorphisms as susceptibility markers for metabolic syndrome (MetS) and type 2 diabetes mellitus (T2DM) in Mexican population. Three PLA2G2A gene polymorphisms (rs876018, rs3753827 and rs11573156) were genotyped by 5' exonuclease TaqMan assays in a group of 338 patients with T2DM, 460 individuals with MetS and 366 healthy controls. Under codominant 1(codom1), dominant (dom) and additive (add) models adjusted by age, gender, body mass index (BMI), smoking habit, and hypertension, the rs876018T allele was associated with increased risk of MetS [Odds Ratio (OR)=1.66, Pcodom1=0.005; OR=1.67, Pdom=0.003; OR=1.49, Padd=0.005] as compared to controls. On the other hand, under several models adjusted by the same variables, the rs3753827A (OR=1.52, Pcodom1=0.039 and OR=1.49, Pdom=0.039) and rs11573156C alleles (OR=6.46, Pcodom1=0.013; OR=6.70, Pcodom2=0.009; OR=6.65, Pdom=0.009) were associated with increased risk of T2DM when compared with controls. In addition, the rs876018T allele was associated with hypercholesterolemia (Pdom=0.017, Padd=0.009) and risk of subclinical atherosclerosis (SA) (Pdom=0.041) in MetS when compared with controls. Also, this allele was associated with SA in T2DM patients (Pdom=0.007). The TAG haplotype was significantly associated with increased risk of MetS (OR=1.54, P=0.006). Results suggest that PLA2G2A polymorphisms are involved in the risk of developing MetS and T2D and are associated with SA in this group of patients.
Assuntos
Aterosclerose/genética , Diabetes Mellitus Tipo 2/genética , Fosfolipases A2 do Grupo II/genética , Hipercolesterolemia/genética , Síndrome Metabólica/genética , Frequência do Gene , Estudos de Associação Genética , Predisposição Genética para Doença , Genótipo , Humanos , Desequilíbrio de Ligação , Lipogênese , Lipólise , México , Polimorfismo de Nucleotídeo ÚnicoRESUMO
AIM: The effect of interleukin 33 (IL-33) in the inflammatory process generates significant interest in the potential significance of IL-33 as a biomarker for coronary artery disease (CAD). Here, our objective was to analyze whether IL-33 gene polymorphisms are associated with premature CAD in a case-control association study. METHODS: Four IL-33 polymorphisms (rs7848215, rs16924144, rs16924159 and rs7044343) were genotyped by 5' exonuclease TaqMan assays in 1095 patients with premature CAD and 1118 controls. RESULTS: The rs7044343 T allele was significantly associated with a diminished risk of premature CAD (OR = 0.81, 95% CI: 0.69-0.97, Pdom = 0.020; OR = 0.85, 95% CI: 0.75-0.96, Padd = 0.019) and central obesity (OR = 0.74, 95% CI: 0.58-0.93, Pdom = 0.0007), respectively. When patients were divided into groups with and without type 2 diabetes mellitus (T2DM), the rs7044343 T allele was associated with a reduced risk of premature CAD in patients without (OR = 0.85, 95% CI: 0.73-0.99, Padd = 0.038) and with T2DM (OR = 0.61, 95% CI: 0.38-0.97, Pdom = 0.039; OR = 0.69, 95% CI: 0.49-0.97, Padd = 0.035). In order to establish the functional effect of the rs7044343 polymorphism, the production of IL-33 was determined in monocytes of selected individuals. Monocytes from individuals with rs7044343 CC genotype produced higher levels of IL-33 than monocytes from individuals with other genotypes. CONCLUSION: The results suggest that the IL-33 rs7044343 T allele could be a susceptibility marker for premature CAD and central obesity. The rs7044343 polymorphism could be involved in regulating the production of IL-33.
Assuntos
Doença da Artéria Coronariana/genética , Predisposição Genética para Doença , Interleucina-33/genética , Obesidade Abdominal/genética , Polimorfismo de Nucleotídeo Único , Adulto , Alelos , Estudos de Casos e Controles , Feminino , Marcadores Genéticos/genética , Humanos , Inflamação , Masculino , Pessoa de Meia-Idade , Monócitos/metabolismo , Polimorfismo Genético , Risco , Tomografia Computadorizada por Raios XRESUMO
Ulcerative colitis (UC) is a chronic condition of unknown etiology and a polygenic disease. The interleukin 27 (IL-27) have been implicated in the pathogenesis of several autoimmune diseases including inflammatory bowel disease. Several polymorphisms of IL-27 have been associated with several types of cancer and immune disorders. The aim of the present study was to evaluate the association between IL-27 gene polymorphisms and the development of UC. Four polymorphisms of IL-27p28 gene (rs181206, rs26528, rs17855750, and rs40837) and three of the Epstein-Barr virus-induced gene 3 (EBI3) (rs428253, rs4740, and rs4905) were genotyped by 5' exonuclease TaqMan genotyping assays on an ABI Prism 7900HT Fast Real-Time PCR System in 375 Mexican patients with UC and 1599 Mexican Mestizo healthy unrelated individuals. IL-27 levels were determined in 458 healthy controls. Under recessive model adjusted by age and gender, the IL-27p28 rs17855750 polymorphism was associated with decreased risk of developing UC (OR=0.27, 95% CI: 0.06-1.13, P=0.031). On the other hand, under recessive models adjusted by age and gender, the EBI3 rs428253 (OR=0.54, 95% CI: 0.29-0.99, P=0.035), rs4740 (OR=0.60, 95% CI: 0.36-1.01, P=0.046) and rs4905 (OR=0.59, 95% CI: 0.35-1.01, P=0.043) were associated with decreased risk of developing UC. Similar levels of IL-27 were observed among the genotypes of the studied polymorphisms. IL-27 polymorphisms might play a protective role for the development of UC in the Mexican population.
Assuntos
Colite Ulcerativa/genética , Interleucina-27/genética , Interleucinas/genética , Antígenos de Histocompatibilidade Menor/genética , Adulto , Feminino , Frequência do Gene , Predisposição Genética para Doença , Genótipo , Humanos , Masculino , México , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Risco , Adulto JovemRESUMO
The CC chemokine monocyte chemoattractant protein (MCP)-1/CCL2 is involved in the formation, progression, and destabilization of atheromatous plaques and plays an essential role in postinfarction remodeling. The aim of the present study was to evaluate the role of MCP-1 gene polymorphisms as susceptibility markers for premature coronary artery disease (CAD) and cardiovascular risk factors in the Mexican population. Four MCP-1 gene polymorphisms (rs1024611, rs2857654, rs3760396, and rs1024610) were genotyped by 5' exonuclease TaqMan assays in a group of 1072 patients with premature CAD, and 1082 healthy unrelated controls (with negative calcium score by computed tomography) seeking for associations with premature CAD and other metabolic and cardiovascular risk factors using logistic regression analyses. MCP-1 polymorphism frequencies were similar in premature CAD patients and healthy controls. When the analysis included only those premature CAD patients without type 2 diabetes mellitus (T2DM), the rs1024610 polymorphism was associated with increased risk of developing premature CAD under dominant and additive models adjusted by age and gender (OR=1.33, Pdom=0.040 and OR=1.34, Padd=0.027). The effect of the MCP-1 polymorphisms on various metabolic cardiovascular risk factors and metabolic parameters was explored separately in controls, and premature CAD. In this analysis adjusted by age and gender, the rs3760396 CC genotype was associated with low levels of gamma-glutamyl transpeptidase (P=0.002), whereas, the rs1024610 TT genotype was associated with decreased risk of T2DM (P=0.035) in premature CAD patients. One haplotype (CATG) was associated with increased risk of developing premature CAD (OR=1.44, P=0.0019). In summary, in our study, the rs1024610 polymorphism was associated with increased risk of developing premature CAD only in those patients without T2DM. The four MCP-1 polymorphisms were in high linkage disequilibrium and one haplotype was significantly associated with risk of developing premature CAD.
Assuntos
Quimiocina CCL2/genética , Doença da Artéria Coronariana/epidemiologia , Doença da Artéria Coronariana/genética , Estudos de Associação Genética , Predisposição Genética para Doença , Polimorfismo de Nucleotídeo Único , Alelos , Biomarcadores , Estudos de Casos e Controles , Comorbidade , Doença da Artéria Coronariana/diagnóstico , Feminino , Frequência do Gene , Genótipo , Haplótipos , Humanos , Masculino , México/epidemiologia , Pessoa de Meia-Idade , Razão de Chances , Risco , Tomografia Computadorizada por Raios XRESUMO
Silent myocardial ischemia (SMI) is a multifactorial and polygenic disorder that results from an excessive inflammatory response. Considering the prominent role of IL-1ß, IL-1F10 and IL-1RN as regulators of the inflammatory process and vascular physiology, the aim of the present study was to analyze whether IL-1ß, IL-1F10 and IL-1RN single nucleotide polymorphisms (SNPs) are associated with SMI. One polymorphism was associated with risk of SMI. Under co-dominant, recessive and additive models, the IL-1ß-511 T>C polymorphism was associated with increased risk of SMI when compared to healthy controls (OR=4.68, 95%CI=2.21-9.92, pCCo-dom=0.0048; OR=3.97, 95%CI=1.97-7.99, pCRec=0.0024; OR=2.02, 95%CI=1.41-2.90, pCAdd=0.0024, respectively). All models were adjusted for gender, age and smoking. Linkage disequilibrium analysis showed four haplotypes (CTCC, CCTC, CCCT and CTCC) with increased frequency in SMI patients when compared to healthy controls (OR=2.53, 95%CI=1.47-4.36, pC=0.0009, OR=2.34, 95%CI=1.15-4.74, pC=0.02, OR=2.44, 95%CI=1.14-5.18, pC=0.02, OR=5.11, 95%CI=1.37-19.05, pC=0.01, respectively). In summary, our data suggest that the IL-1ß-511 T>C polymorphism plays an important role in the development of SMI in diabetic patients. In addition, in our study was possible to distinguish one protective and four risk haplotypes for development of SMI.
Assuntos
Diabetes Mellitus/fisiopatologia , Predisposição Genética para Doença/genética , Interleucina-1beta/genética , Isquemia Miocárdica/genética , Polimorfismo de Nucleotídeo Único , Idoso , Feminino , Frequência do Gene , Genótipo , Haplótipos , Humanos , Desequilíbrio de Ligação , Masculino , Pessoa de Meia-Idade , Isquemia Miocárdica/fisiopatologia , Fatores de RiscoRESUMO
AIM: The role of interleukin 17A (IL-17A) in the inflammatory process has caused interest in the potential significance of IL-17A as a biomarker for coronary artery disease (CAD). The aim of the present study was to evaluate the role of IL-17A gene polymorphisms as susceptibility markers for CAD in the Mexican population. METHODS: Four IL-17A gene polymorphisms (rs8193036, rs3819024, rs2275913 and rs8193037) were genotyped by 5' exonuclease TaqMan assays in a group of 900 patients with premature CAD and 667 healthy controls (with negative calcium score by computed tomography), seeking associations with CAD and other metabolic and cardiovascular risk factors using logistic regression analyses. RESULTS: No single IL-17A polymorphism was associated with premature CAD, however two haplotypes (CAGG and TAGA) were significantly associated with increased risk of premature CAD (OR = 1.35, 95% CI: 1.00-1.84, P = 0.018 and OR = 2.09, 95% CI: 1.16-3.76, P = 0.003, respectively). Moreover, rs3819024 was associated with increased levels of visceral abdominal fat (P = 0.002) and rs8193036 was significantly associated with risk of central obesity (P = 0.020), hypertriglyceridemia (P = 0.027), and metabolic syndrome (P = 0.027) in the premature CAD group, under dominant models adjusted by age, gender, BMI, smoking history, alcohol consumption, and treatment. CONCLUSION: The results suggest that IL-17A haplotypes are involved in the risk of developing premature CAD and some IL-17A polymorphisms are associated with cardiovascular risk factors in Mexican individuals with premature CAD.
Assuntos
Doença da Artéria Coronariana/genética , Haplótipos , Interleucina-17/genética , Idade de Início , Doença da Artéria Coronariana/epidemiologia , Feminino , Humanos , Masculino , México , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo ÚnicoRESUMO
BACKGROUND: Rheumatic heart disease (RHD) is an autoimmune sequel of group A streptococcal infection that has been associated with the presence of some major histocompatibility complex (MHC) genes. Thus, the aim of the present study was to investigate the role of class II alleles in the genetic susceptibility to RHD in Mexican patients and establish the relationship of these alleles with the pattern of valve damage. METHODS: HLA-DR, -DQA1 and -DQB1 allele frequencies were determined by PCR-SSO reverse dot blot and PCR-SSP in 98 Mexican Mestizo patients with RHD and 99 healthy controls. Patients were divided into mitral valve damage (n=46), multivalvular lesion (n=49) and aortic damage (n=3). RESULTS: RHD patients presented an HLA-DR16 increased frequency (pC=0.009, OR=3.9) and a decreased HLA-DR11 frequency (pC=0.018) when compared to healthy controls. HLA-DR16 subtyping showed that DRB1*1602 was the DR16 allele increased in patients (pC=0.007, OR=5.3). Haplotype analysis showed increased frequency of DR16-DQA1*0501-DQB1*0301 in RHD patients when compared to healthy controls (pC=0.011). HLA-DR16 frequency remained significantly increased on patients with multivalvular lesion (pC=0.004, OR=4.8). CONCLUSIONS: Our data suggest an important participation of Amerindian autochthonous HLA-DR16 (DRB1*1602) allele and DR16-DQA1*0501-DQB1*0301 haplotype as markers for RHD genetic susceptibility in the Mexican Mestizo population. HLA-DR16 allele could also play an important role in determining the pattern of valve damage on these patients.
Assuntos
Genes MHC da Classe II , Predisposição Genética para Doença , Indígenas Norte-Americanos/genética , Cardiopatia Reumática/genética , População Branca/genética , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Feminino , Frequência do Gene , Haplótipos , Humanos , Masculino , México , Pessoa de Meia-IdadeRESUMO
Coronary artery disease (CAD) is a multifactorial and polygenic disorder that results from an excessive inflammatory response. We analyzed whether interleukin-24 (IL-24) gene polymorphisms are associated with premature CAD in a case-control association study. Four polymorphisms (rs1150253, rs1150256, rs1150258, and rs3762344) of the IL-24 gene were analyzed by 5' exonuclease TaqMan genotyping assays in a group of 952 patients with premature CAD, 284 individuals with subclinical atherosclerosis (SA), and 912 controls. The studied polymorphisms were not associated with the risk of premature CAD or SA (P>0.05). Under dominant models adjusted for age, sex, body mass index, and medication, the polymorphisms were associated with cardiometabolic parameters and cardiovascular risk factors. Three polymorphisms (rs1150253, rs1150256, and rs3762344) were associated with hypertension and increased levels of systolic blood pressure in controls. In SA, 2 polymorphisms (rs1150256 and rs3762344) were associated with type 2 diabetes mellitus, gamma-glutamyl transpeptidase (GGT), and alkaline phosphatase, whereas rs1150253 was associated with GGT and type 2 diabetes mellitus and rs1150258 with GGT and alkaline phosphatase. In premature CAD, the 4 polymorphisms were associated with total cholesterol >200 mg/dL, low-density lipoprotein cholesterol (LDL-C), and GGT, whereas rs1150256 was associated also with ApoA. On the other hand, rs1150258 was associated with ApoA, LDL-C >100 mg/dL, and apoB/apoA ratio, and rs3762344 with ApoA, apoB/apoA ratio, LDL-C >100 mg/dL, and total cholesterol. On the basis of single-nucleotide polymorphism functional prediction software, rs1150253 and rs1150258 polymorphisms seem to be functional. The 4 studied polymorphisms were in linkage disequilibrium and had a similar haplotype distribution in patients and controls. Our study demonstrates the association of IL-24 polymorphisms with metabolic and cardiovascular risk factors in individuals with premature CAD, SA, and controls.
Assuntos
Aterosclerose/genética , Doença da Artéria Coronariana/genética , Interleucinas/genética , Estudos de Casos e Controles , Diabetes Mellitus Tipo 2/genética , Feminino , Predisposição Genética para Doença , Genótipo , Haplótipos , Humanos , Desequilíbrio de Ligação , Masculino , México , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Risco , Fatores de RiscoRESUMO
Coronary artery disease (CAD) is a multifactorial disorder that results from an excessive inflammatory response. Secretory phospholipase A2-V (sPLA2-V) encoded by PLA2G5 gene promotes diverse proinflammatory processes. The aim of the present study was to analyze if PLA2G5 gene polymorphisms are associated with premature CAD. Three PLA2G5 polymorphisms (rs11573187, rs2148911, and rs11573191) were analyzed in 707 patients with premature CAD and 749 healthy controls. Haplotypes were constructed after linkage disequilibrium analysis. Under dominant, recessive, and additive models, the rs11573191 polymorphism was associated with increased risk of premature CAD (OR = 1.51, P(dom) = 3.5 × 10(-3); OR = 2.95, P(rec) = 0.023; OR = 1.51, P(add) = 1.2 × 10(-3)). According to the informatics software, this polymorphism had a functional effect modifying the affinity of the sequence by the MZF1 transcription factor. PLA2G5 polymorphisms were in linkage disequilibrium and the CGA haplotype was associated with increased risk of premature CAD (OR = 1.49, P = 0.0023) and with hypertension in these patients (OR = 1.75, P = 0.0072). Our results demonstrate the association of the PLA2G5 rs11573191 polymorphism with premature CAD. In our study, it was possible to distinguish one haplotype associated with increased risk of premature CAD and hypertension.
Assuntos
Doença da Artéria Coronariana/genética , Estudos de Associação Genética , Fosfolipases A2 do Grupo V/genética , Hipertensão/genética , Adulto , Doença da Artéria Coronariana/patologia , Feminino , Frequência do Gene , Predisposição Genética para Doença , Haplótipos , Humanos , Hipertensão/patologia , Masculino , México , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo ÚnicoRESUMO
Interleukin (IL)-20 belongs to the IL-10 family and is a potent immunomodulatory cytokine with implications for pathogenesis in the inflammatory bowel disease (IBD). The interleukin 20 gene is located within a 200kb region of q31-32 locus of chromosome 1. No previous studies have reported this novel association between ulcerative colitis (UC) and IL-20 polymorphisms. In the present work, we evaluated the role of IL-20 gene polymorphisms as susceptibility markers for UC. Three polymorphisms of IL-20 gene (rs2981573, rs2232360, rs1518108) were genotyped by 5' exonuclease TaqMan genotyping assays on an ABI Prism 7900 HT Fast Real-Time PCR system in a group of 198 Mexican Mestizo patients with UC and 698 ethnically matched healthy unrelated individuals with no family history of UC. We found significant decreased frequencies of two IL-20 genotypes: GG (rs2981573) [10.6% vs. 17.6%, p=0.017, OR=0.55, 95% CI: 0.33-0.93] and GG (rs2232360) [10.6% vs. 17.6%, p=0.017, OR=0.55, 95% CI: 0.33-0.93] in UC patients as compared to healthy controls. No significant differences of gene frequencies were found between UC patients and healthy controls in the rs1518108 polymorphism. In the subgroup analysis, no differences were found between the IL-20 genotypes and the clinical characteristics of UC. The results suggest that the GG genotypes of the IL-20 polymorphisms (rs2981573 and rs2232360) might have an important role in the development of UC in the Mexican population.