The mechanisms that regulate disease progression during hepatitis C virus(HCV)infection and the response to treatment are not clearly identified.Numerous studies have demonstrated that a strong host immune response ag...The mechanisms that regulate disease progression during hepatitis C virus(HCV)infection and the response to treatment are not clearly identified.Numerous studies have demonstrated that a strong host immune response against HCV favors HCV clearance.In addition,genetic factors and metabolic machinery,particularly cholesterol modulation,are involved in HCV infection.It is likely that the interplay between all of these factors contributes to the outcome of HCV infection.In recent years,the world has experienced its largest epidemic of obesity.Mexico and the United States are the leading sufferers from this epidemic at the global level.Obesity is associated with the development ofnumerous pathologies including hypercholesterolemia which is one of the eight most important risk factors for mortality in Mexico.This may be related to the course of HCV infection in this population.Here,we focus on the urgent need to study the progression of HCV infection in relation to ethnic characteristics.Discoveries are discussed that hold promise in identifying immune,metabolic and genetic factors that,in conjunction,could be therapeutic targets or predictors of the progression of HCV infection.展开更多
BACKGROUND Cholesterol is related to improvements in the rate of sustained virological response and a robust immune response against the hepatitis C virus(HCV).APOE gene polymorphisms regulate cholesterol levels modif...BACKGROUND Cholesterol is related to improvements in the rate of sustained virological response and a robust immune response against the hepatitis C virus(HCV).APOE gene polymorphisms regulate cholesterol levels modifying the course of the HCV infection.The relationship between cholesterol,APOE alleles,and the outcome of HCV infection has not been evaluated in the admixed population of Mexico.AIM To investigate the role of APOE-ε2,-ε3,and-ε4 alleles and the metabolic profile in the outcome of HCV infection.METHODS A total of 299 treatment-na?ve HCV patients were included in this retrospective study.Patients were stratified in chronic hepatitis C(CHC)(n=206)and spontaneous clearance(SC)(n=93).A clinical record was registered.Biochemical tests were assessed by dry chemistry assay.APOE genotypes were determined using a Real-Time polymerase chain reaction assay.RESULTS Total cholesterol,low-density lipoprotein cholesterol(LDL-c),triglycerides,and hypercholesterolemia were higher in SC than CHC patients as well as the frequency of the APOEε4 allele(12.4%vs 7.3%).SC patients were overweight(54.8%).Theε4 allele was associated with SC(OR=0.55,95%CI:0.31-0.98,P=0.042)and mild fibrosis(F1-F2)in CHC patients(OR 0.091,95%CI 0.01-0.75,P=0.020).LDL-c≥101.5 mg/dL(OR=0.20,95%CI:0.10-0.41,P<0.001)and BMI≥26.6 kg/m2(OR=0.37,95%CI:0.18-0.76,P<0.001)were associated with SC status;while ALT≥50.5 IU/L was negatively associated(OR=5.67,95%CI:2.69-11.97,P<0.001).CONCLUSION In SC patients,the APOEε4 allele and LDL-c conferred a protective effect in the course of the HCV infection in the context of excess body weight.展开更多
AIM To analyze the association of the CD36 polymorphism(rs1761667) with dietary intake and liver fibrosis(LF) in chronic hepatitis C(CHC) patients. METHODS In this study, 73 patients with CHC were recruited. The CD36 ...AIM To analyze the association of the CD36 polymorphism(rs1761667) with dietary intake and liver fibrosis(LF) in chronic hepatitis C(CHC) patients. METHODS In this study, 73 patients with CHC were recruited. The CD36 genotype(G > A) was determined by a TaqM an real-time PCR system. Dietary assessment was carried out using a three-day food record to register the daily intake of macronutrients. Serum lipids and liver enzymes were measured by a dry chemistry assay. LF evaluated by transient elastography(Fibroscan~)and APRI score was classified as mild LF(F1-F2) and advanced LF(F3-F4).RESULTS Overall, the CD36 genotypic frequencies were AA(30.1%), AG(54.8%), and GG(15.1%), whereas the allelic A and G frequencies were 57.5% and 42.5%, respectively. CHC patients who were carriers of the CD36 AA genotype had a higher intake of calories attributable to total fat and saturated fatty acids than those with the non-AA genotypes. Additionally, aspartate aminotransferase(AST) serum values were higher in AA genotype carriers compared to non-AA carriers(91.7 IU/L vs 69.8 IU/L, P = 0.02). Moreover, the AA genotype was associated with an increase of 30.23 IU/L of AST(β = 30.23, 95%CI: 9.0-51.46, P = 0.006). Likewise, the AA genotype was associated with advanced LF compared to the AG(OR = 3.60, 95%CI: 1.16-11.15, P = 0.02) or AG + GG genotypes(OR = 3.52, 95%CI: 1.18-10.45, P = 0.02).CONCLUSION This study suggests that the CD36(rs1761667) AA genotype is associated with higher fat intake and more instances of advanced LF in CHC patients.展开更多
BACKGROUND Dyslipidemias are metabolic abnormalities associated with chronic diseases caused by genetic and environmental factors.The Mexican population displays regional differences according to ethnicity with an imp...BACKGROUND Dyslipidemias are metabolic abnormalities associated with chronic diseases caused by genetic and environmental factors.The Mexican population displays regional differences according to ethnicity with an impact on the type of dyslipidemia.AIM To define the main dyslipidemias,the frequency of lipid-related risk alleles,and their association with hyperlipidemic states among different ethnic groups in West Mexico.METHODS In a retrospective study,1324 adults were selected to compare dyslipidemias and lipid-related gene polymorphisms.Demographic,clinical,and laboratory data were collected.A subgroup of 196 normal weight subjects without impaired glucose was selected for the association analyses.Genotyping was determined by allelic discrimination assay.RESULTS Hypercholesterolemia was the most prevalent dyslipidemia(42.3%).The frequency of the risk alleles associated with hypoalphalipoproteinemia(ABCA1)and hypercholesterolemia(APOE,LDLR)was higher in the Native Americans(P=0.047).In contrast,the Mestizos with European ancestry showed a higher frequency of the risk alleles for hypertriglyceridemia(APOE2,MTTP)(P=0.045).In normal weight Mestizo subjects,the APOB TT and LDLR GG genotypes were associated risk factors for hypercholesterolemia(OR=5.33,95%CI:1.537-18.502,P=0.008 and OR=3.90,95%CI:1.042-14.583,P=0.043,respectively),and displayed an increase in low-density lipoprotein cholesterol levels(APOB:β=40.39,95%CI:14.415-66.366,P=0.004;LDLR:β=20.77,95%CI:5.763-35.784,P=0.007).CONCLUSION Gene polymorphisms and dyslipidemias showed a differential distribution.Regional primary health care strategies are required to mitigate their prevalence considering the genetic and environmental features which could have important implications for personalized medicine within the new era of precision medicine.展开更多
基金Supported by The National Council of Science and Technol-ogy(CONACYT-FONDO SECTORIAL,Mexico),Grant No.Salud-2010-1-139085 to Roman SCONACYT-CIENCIA BA-SICA,Mexico,Grant No.127229,COECYTJAL-UDG,Mexico,Grants No.S-2010-1-849,CONACYT-INFR,Mexico and Grant No.188240 to Fierro NA
文摘The mechanisms that regulate disease progression during hepatitis C virus(HCV)infection and the response to treatment are not clearly identified.Numerous studies have demonstrated that a strong host immune response against HCV favors HCV clearance.In addition,genetic factors and metabolic machinery,particularly cholesterol modulation,are involved in HCV infection.It is likely that the interplay between all of these factors contributes to the outcome of HCV infection.In recent years,the world has experienced its largest epidemic of obesity.Mexico and the United States are the leading sufferers from this epidemic at the global level.Obesity is associated with the development ofnumerous pathologies including hypercholesterolemia which is one of the eight most important risk factors for mortality in Mexico.This may be related to the course of HCV infection in this population.Here,we focus on the urgent need to study the progression of HCV infection in relation to ethnic characteristics.Discoveries are discussed that hold promise in identifying immune,metabolic and genetic factors that,in conjunction,could be therapeutic targets or predictors of the progression of HCV infection.
基金Supported by Programa para el Desarrollo Profesional Docente(PRODEP)to Gonzalez-Aldaco K,No.UDG-PTC-1422Consejo Nacional de Ciencia y Tecnología(CONACYT)to Panduro A,No.2017-01-5254
文摘BACKGROUND Cholesterol is related to improvements in the rate of sustained virological response and a robust immune response against the hepatitis C virus(HCV).APOE gene polymorphisms regulate cholesterol levels modifying the course of the HCV infection.The relationship between cholesterol,APOE alleles,and the outcome of HCV infection has not been evaluated in the admixed population of Mexico.AIM To investigate the role of APOE-ε2,-ε3,and-ε4 alleles and the metabolic profile in the outcome of HCV infection.METHODS A total of 299 treatment-na?ve HCV patients were included in this retrospective study.Patients were stratified in chronic hepatitis C(CHC)(n=206)and spontaneous clearance(SC)(n=93).A clinical record was registered.Biochemical tests were assessed by dry chemistry assay.APOE genotypes were determined using a Real-Time polymerase chain reaction assay.RESULTS Total cholesterol,low-density lipoprotein cholesterol(LDL-c),triglycerides,and hypercholesterolemia were higher in SC than CHC patients as well as the frequency of the APOEε4 allele(12.4%vs 7.3%).SC patients were overweight(54.8%).Theε4 allele was associated with SC(OR=0.55,95%CI:0.31-0.98,P=0.042)and mild fibrosis(F1-F2)in CHC patients(OR 0.091,95%CI 0.01-0.75,P=0.020).LDL-c≥101.5 mg/dL(OR=0.20,95%CI:0.10-0.41,P<0.001)and BMI≥26.6 kg/m2(OR=0.37,95%CI:0.18-0.76,P<0.001)were associated with SC status;while ALT≥50.5 IU/L was negatively associated(OR=5.67,95%CI:2.69-11.97,P<0.001).CONCLUSION In SC patients,the APOEε4 allele and LDL-c conferred a protective effect in the course of the HCV infection in the context of excess body weight.
基金Supported by Promep-University of Guadalajara to Arturo Panduro,No.UDG-CA-478
文摘AIM To analyze the association of the CD36 polymorphism(rs1761667) with dietary intake and liver fibrosis(LF) in chronic hepatitis C(CHC) patients. METHODS In this study, 73 patients with CHC were recruited. The CD36 genotype(G > A) was determined by a TaqM an real-time PCR system. Dietary assessment was carried out using a three-day food record to register the daily intake of macronutrients. Serum lipids and liver enzymes were measured by a dry chemistry assay. LF evaluated by transient elastography(Fibroscan~)and APRI score was classified as mild LF(F1-F2) and advanced LF(F3-F4).RESULTS Overall, the CD36 genotypic frequencies were AA(30.1%), AG(54.8%), and GG(15.1%), whereas the allelic A and G frequencies were 57.5% and 42.5%, respectively. CHC patients who were carriers of the CD36 AA genotype had a higher intake of calories attributable to total fat and saturated fatty acids than those with the non-AA genotypes. Additionally, aspartate aminotransferase(AST) serum values were higher in AA genotype carriers compared to non-AA carriers(91.7 IU/L vs 69.8 IU/L, P = 0.02). Moreover, the AA genotype was associated with an increase of 30.23 IU/L of AST(β = 30.23, 95%CI: 9.0-51.46, P = 0.006). Likewise, the AA genotype was associated with advanced LF compared to the AG(OR = 3.60, 95%CI: 1.16-11.15, P = 0.02) or AG + GG genotypes(OR = 3.52, 95%CI: 1.18-10.45, P = 0.02).CONCLUSION This study suggests that the CD36(rs1761667) AA genotype is associated with higher fat intake and more instances of advanced LF in CHC patients.
文摘BACKGROUND Dyslipidemias are metabolic abnormalities associated with chronic diseases caused by genetic and environmental factors.The Mexican population displays regional differences according to ethnicity with an impact on the type of dyslipidemia.AIM To define the main dyslipidemias,the frequency of lipid-related risk alleles,and their association with hyperlipidemic states among different ethnic groups in West Mexico.METHODS In a retrospective study,1324 adults were selected to compare dyslipidemias and lipid-related gene polymorphisms.Demographic,clinical,and laboratory data were collected.A subgroup of 196 normal weight subjects without impaired glucose was selected for the association analyses.Genotyping was determined by allelic discrimination assay.RESULTS Hypercholesterolemia was the most prevalent dyslipidemia(42.3%).The frequency of the risk alleles associated with hypoalphalipoproteinemia(ABCA1)and hypercholesterolemia(APOE,LDLR)was higher in the Native Americans(P=0.047).In contrast,the Mestizos with European ancestry showed a higher frequency of the risk alleles for hypertriglyceridemia(APOE2,MTTP)(P=0.045).In normal weight Mestizo subjects,the APOB TT and LDLR GG genotypes were associated risk factors for hypercholesterolemia(OR=5.33,95%CI:1.537-18.502,P=0.008 and OR=3.90,95%CI:1.042-14.583,P=0.043,respectively),and displayed an increase in low-density lipoprotein cholesterol levels(APOB:β=40.39,95%CI:14.415-66.366,P=0.004;LDLR:β=20.77,95%CI:5.763-35.784,P=0.007).CONCLUSION Gene polymorphisms and dyslipidemias showed a differential distribution.Regional primary health care strategies are required to mitigate their prevalence considering the genetic and environmental features which could have important implications for personalized medicine within the new era of precision medicine.