Obesity is associated with the Arg389Gly ADRB1 but not with the Trp64Arg ADRB3 polymorphism in children from San Luis Potosí and León,México
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摘要
This research was designed to analyze the possible associations of Arg389 Gly ADRB1 and Trp64 Arg ADRB3polymorphisms in children with obesity.A cross-sectional study included 1,046 school-age Mexican participants(6-12 years old) from the cities of San Luis Potosi and Leon.Children were classified as non-obese or obese according to their body mass index(BMI) percentile;obese children had a BMI≥95th percentile for sex and age.Biochemical data were collected.Polymorphisms were detected using TaqMan qPCR assay.A logistic regression analysis was used to calculate the risk of obesity based on genotypes.Differences were found between groups where obese children had a significant increase in systolic and diastolic blood pressure,fasting plasma glucose,insulin,HOMAIR,LDL-cholesterol,triglycerides,and lower HDL-cholesterol compared with the normal weight group(P < 0.05).The distribution of allele frequency in the population was Arg = 87.4 and Gly = 12.6(Hardy Weinberg equilibrium x~2= 3.16,P = 0.07);Trp = 81.5 and Arg= 18.5(Hardy Weinberg equilibrium x~2 = 2.2,P = 0.14) for ADRB1 and ADRB3,respectively.Even though no different frequencies of Arg389 Gly polymoiphism between groups were found(P = 0.08),children carriers of one Gly389,ADRB1 allele had a risk for obesity of OR = 1.40(95%CI,1.03-1.90,P =0.03) after adjustment for age and gender.No other association was found for Trp64 Arg ADRB3 polymorphism.Only the Arg389 Gly ADRB1 polymorphism was associated with risk for obesity in Mexican children.
This research was designed to analyze the possible associations of Arg389 Gly ADRB1 and Trp64 Arg ADRB3polymorphisms in children with obesity.A cross-sectional study included 1,046 school-age Mexican participants(6-12 years old) from the cities of San Luis Potosi and Leon.Children were classified as non-obese or obese according to their body mass index(BMI) percentile;obese children had a BMI≥95th percentile for sex and age.Biochemical data were collected.Polymorphisms were detected using TaqMan qPCR assay.A logistic regression analysis was used to calculate the risk of obesity based on genotypes.Differences were found between groups where obese children had a significant increase in systolic and diastolic blood pressure,fasting plasma glucose,insulin,HOMAIR,LDL-cholesterol,triglycerides,and lower HDL-cholesterol compared with the normal weight group(P < 0.05).The distribution of allele frequency in the population was Arg = 87.4 and Gly = 12.6(Hardy Weinberg equilibrium x~2= 3.16,P = 0.07);Trp = 81.5 and Arg= 18.5(Hardy Weinberg equilibrium x~2 = 2.2,P = 0.14) for ADRB1 and ADRB3,respectively.Even though no different frequencies of Arg389 Gly polymoiphism between groups were found(P = 0.08),children carriers of one Gly389,ADRB1 allele had a risk for obesity of OR = 1.40(95%CI,1.03-1.90,P =0.03) after adjustment for age and gender.No other association was found for Trp64 Arg ADRB3 polymorphism.Only the Arg389 Gly ADRB1 polymorphism was associated with risk for obesity in Mexican children.
This research was designed to analyze the possible associations of Arg389 Gly ADRB1 and Trp64 Arg ADRB3polymorphisms in children with obesity.A cross-sectional study included 1,046 school-age Mexican participants(6-12 years old) from the cities of San Luis Potosi and Leon.Children were classified as non-obese or obese according to their body mass index(BMI) percentile;obese children had a BMI≥95th percentile for sex and age.Biochemical data were collected.Polymorphisms were detected using TaqMan qPCR assay.A logistic regression analysis was used to calculate the risk of obesity based on genotypes.Differences were found between groups where obese children had a significant increase in systolic and diastolic blood pressure,fasting plasma glucose,insulin,HOMAIR,LDL-cholesterol,triglycerides,and lower HDL-cholesterol compared with the normal weight group(P < 0.05).The distribution of allele frequency in the population was Arg = 87.4 and Gly = 12.6(Hardy Weinberg equilibrium x~2= 3.16,P = 0.07);Trp = 81.5 and Arg= 18.5(Hardy Weinberg equilibrium x~2 = 2.2,P = 0.14) for ADRB1 and ADRB3,respectively.Even though no different frequencies of Arg389 Gly polymoiphism between groups were found(P = 0.08),children carriers of one Gly389,ADRB1 allele had a risk for obesity of OR = 1.40(95%CI,1.03-1.90,P =0.03) after adjustment for age and gender.No other association was found for Trp64 Arg ADRB3 polymorphism.Only the Arg389 Gly ADRB1 polymorphism was associated with risk for obesity in Mexican children.
引文
[1]Ogden CL,Carroll MD,Curtin LR,et al.Prevalence of high body mass index in US children and adolescents,2007-2008[J].JAMA,2010,303(3):242-249.
[2]Franks PW,Hanson RL,Knowler WC,et al.Childhood obesity,other cardiovascular risk factors,and premature death[J].N Engl J Med,2010,362(6):485-493.
[3]Gutierrez JP,Rivera-Dommarco J,Shamah-Levy T,et al.Nutrition:Encuesta Nacional de Salud y Nutrition 2012.Resultados Nacionales[J].Cuernavaca,Mexico:Institute Nacional de Salud Publico(MX),2012,129-66.
[4]Pena Reyes ME,Cardenas Barahona EE,Lamadrid PS,et al.Growth status of indigenous school children 6-14 years in the Tarahumara Sierra,Northern Mexico,in 1990 and 2007[J].Ann Hum Biol,2009,36(6):756-769.
[5]Hossain P,Kawar B,El Nahas M.Obesity and diabetes in the developing world—a growing challenge[J].N Engl J Med,2007,356(3):213-215.
[6]Dulloo AG,Seydoux J,Jacquet J.Adaptive thermogenesis and uncoupling proteins:a reappraisal of their roles in fat metabolism and energy balance[J].Physiol Behav,2004,83(4):587-602.
[7]Lima JJ,Feng H,Duckworth L,et al.Association analyses of adrenergic receptor polymorphisms with obesity and metabolic alterations[J].Metabolism,2007,56(6):757-765.
[8]Chou YC,Tsai CN,Lee YS,et al.Association of adrenergic receptor gene polymorphisms with adolescent obesity in Taiwan[J].Pediatr Int,2012,54(1):111-116.
[9]Park HS,Kim Y,Lee C.Single nucleotide variants in the beta2-adrenergic and beta3-adrenergic receptor genes explained18.3%of adolescent obesity variation[J].J Hum Genet,2005,50(7):365-369.
[10]Dionne IJ,Garant MJ,Nolan AA,et al.Association between obesity and a polymorphism in the beta(1)-adrenoceptor gene(Gly389Arg ADRB1)in Caucasian women[J].Int J Obes Relat Metab Disord,2002,26(5):633-639.
[11]Mottagui-Tabar S,Hoffstedt J,Brookes AJ,et al.Association of ADRB1 and UCP3 gene polymorphisms with insulin sensitivity but not obesity[J].Horm Res,2008,69(1):31-36.
[12]Peng Y,Xue H,Luo L,et al.Polymorphisms of the betaladrenergic receptor gene are associated with essential hypertension in Chinese[J].Clin Chem Lab Med,2009,47(10):1227-1231.
[13]Song YL,Wu XZ,Guo G,et al.[389A/G polymorphism of the human beta l-adrenergic receptor in patients with acute myocardial infarction][J].Zhonghua Yi Xue Yi Chuan Xue Za Zhi,2007,24(4):422-424.
[14]Fragoso JM,Rodriguez-Perez JM,Perez-Vielma N,et al.Betal adrenergic receptor polymorphisms Arg389Gly and Ser49Gly in the Amerindian and Mestizo populations of Mexico[J].Hum Biol,2005,77(4):515-520.
[15]Li S,Chen W,Srinivasan SR,et al.Influence of lipoprotein lipase gene Ser447Stop and beta1-adrenergic receptor gene Arg389Gly polymorphisms and their interaction on obesity from childhood to adulthood:the Bogalusa Heart Study[J].IntJ Obes(Lond),2006,30(8):1183-1188.
[16]Gjesing AP,Andersen G,Albrechtsen A,et al.Studies of associations between the Arg389Gly polymorphism of the beta 1-adrenergic receptor gene(ADRB1)and hypertension and obesity in 7677 Danish white subjects[J].Diabet Med,2007,24(4):392-397.
[17]Silver K,Mitchell BD,Walston J,et al.TRP64ARG beta 3-adrenergic receptor and obesity in Mexican Americans[J].Hum Genet,1997,101(3):306-311.
[18]de Luis DA,Aller R,Izaola O,et al.Relation of Trp64Arg polymorphism of beta 3-adrenergic receptor gene to adipocytokines and fat distribution in obese patients[J].Ann Nutr Metab,2008,52(4):267-271.
[19]Widen E,Lehto M,Kanninen T,et al.Association of a polymorphism in the beta 3-adrenergic-receptor gene with features of the insulin resistance syndrome in Finns[J].N Engl J Med,1995,333(6):348-351.
[20]Oeveren van-Dybicz AM,Vonkeman HE,Bon MA,et al.Beta3-adrenergic receptor gene polymorphism and type 2 diabetes in a Caucasian population[J].Diabetes Obes Metab,2001,3(1):47-51.
[21]Oizumi T,Daimon M,Saitoh T,et al.,and the Funagata Diabetes Study.Genotype Arg/Arg,but not Trp/Arg,of the Trp64Arg polymorphism of the beta(3)-adrenergic receptor is associated with type 2 diabetes and obesity in a large Japanese sample[J].Diabetes Care,2001,24(9):1579-1583.
[22]Tamaki S,Nakamura Y,Tabara Y,et al.Relationship between metabolic syndrome and Trp64arg polymorphism of the betaadrenergic receptor gene in a general sample:the Shigaraki study[J].Hypertens Res,2006,29(11):891-896.
[23]Ogden CL,Kuczmarski RJ,Flegal KM,et al.Centers for Disease Control and Prevention 2000 growth charts for the United States:improvements to the 1977 National Center for Health Statistics version[J].Pediatrics,2002,109(1):45-60.
[24]Matthews DR,Hosker JP.Rudenski As,et al.Homoeostasis model assessment:insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man[J].Diabetologia,1985,28:412-419.
[25]Rodriguez-Moran M,Guerrero-Romero F,Aradillas-Garcia C,et al.Obesity and family history of diabetes as risk factors of impaired fasting glucose:implications for the early detection of prediabetes[J].Pediatr Diabetes,2010,11(5):331-336.
[26]Tafel J,Branscheid I,Skwarna B,et al.Variants in the human beta 1-,beta 2-,and beta 3-adrenergic receptor genes are not associated with morbid obesity in children and adolescents[J].Diabetes Obes Metab,2004,6(6):452-455.
[27]Xie HG,Dishy V,Sofowora G,et al.Arg389Gly beta 1-adrenoceptor polymorphism varies in frequency among different ethnic groups but does not alter response in vivo[J].Pharmacogenetics,2001,11(3):191-197.
[28]Rasmussen M,Belza A,Almdal T,et al.Change in betaladrenergic receptor protein concentration in adipose tissue correlates with diet-induced weight loss[J].Clin Sci(Lond),2005,108(4):323-329.
[29]Mason DA,Moore JD,Green SA,et al.A gain-of-function polymorphism in a G-protein coupling domain of the human beta 1-adrenergic receptor[J].J Biol Chem,1999,274(18):12670-12674.
[30]Zawodniak-Sza apska M,Stawerska R,Brzezianska E,et al.Association of Trp64Arg polymorphism of beta3-adrenergic receptor with insulin resistance in Polish children with obesity[J].J Pediatr Endocrinol Metab,2008,21(2):147-154.
[31]Kurokawa N,Nakai K,Kameo S,et al.Relationship between the beta3-adrenoceptor gene variant and body fat in Japanese children[J].Tohoku J Exp Med,2003,201(4):271-276.
[32]Kurokawa N,Nakai K,Kameo S,et al.Association of BMI with the beta3-adrenergic receptor gene polymorphism in Japanese:meta-analysis[J].Obes Res,2001,9(12):741-745.
[33]Yamakita M,Ando D,Tang S,et al.The Trp64Arg polymorphism of the beta3-adrenergic receptor gene is associated with weight changes in obese Japanese men:a 4-year follow-up study[J].J Physiol Anthropol,2010,29(4):133-139.
[34]Zhu LY,Hu LY,Li XL,et al.Relationship between Trp64Arg mutation in theβ3-adrenergic receptor gene and metabolic syndrome:a seven-year follow-up study[J].Chin Med J(Engl),2010,123(17):2375-2378.
[35]Kasznicki J,Blasiak J,Majsterek I,et al.The Trp64Arg beta3-adrenergic receptor amino-acid variant is not associated with overweight and type 2 diabetes mellitus in Polish population[J].Exp Clin Endocrinol Diabetes,2005,113(10):593-597.
[36]Biery AJ,Ebbesson SO,Shuldiner AR,et al.The beta--adrenergic receptor TRP64ARG polymorphism and obesity in Alaskan Eskimos[J].Int J Obes Relat Metab Disord,1997,21(12):1176-1179.
[37]Lowe WL Jr,Rotimi CN,Luke A,et al.The beta 3-adrenergic receptor gene and obesity in a population sample of African Americans[J].Int J Obes Relat Metab Disord,2001,25(1):54-60.
[38]Kurokawa N,Young EH,Oka Y,et al.The ADRB3 Trp64Arg variant and BMI:a meta-analysis of 44 833 individuals[J].Int J Obes(Land),2008,32(8):1240-1249.
[39]Martinez-Fierro ML,Beuten J,Leach RJ,et al.Ancestry informative markers and admixture proportions in northeastern Mexico[J].J Hum Genet,2009,54(9):504-509.
[40]Kumar S,Mishra A,Srivastava A,et al.Significant role of ADRB3 rs4994 towards the development of coronary artery disease[J].Coron Artery Dis,2014,25(1):29-34.
[41]Anthony EG,Richard E,Lipkowitz MS,et al.Association of the ADRB2(rs2053044)polymorphism and angiotensinconverting enzyme-inhibitor blood pressure response in the African American Study of Kidney Disease and Hypertension[J].Pharmacogenet Genomics,2015,25(9):444-449.
[2]Franks PW,Hanson RL,Knowler WC,et al.Childhood obesity,other cardiovascular risk factors,and premature death[J].N Engl J Med,2010,362(6):485-493.
[3]Gutierrez JP,Rivera-Dommarco J,Shamah-Levy T,et al.Nutrition:Encuesta Nacional de Salud y Nutrition 2012.Resultados Nacionales[J].Cuernavaca,Mexico:Institute Nacional de Salud Publico(MX),2012,129-66.
[4]Pena Reyes ME,Cardenas Barahona EE,Lamadrid PS,et al.Growth status of indigenous school children 6-14 years in the Tarahumara Sierra,Northern Mexico,in 1990 and 2007[J].Ann Hum Biol,2009,36(6):756-769.
[5]Hossain P,Kawar B,El Nahas M.Obesity and diabetes in the developing world—a growing challenge[J].N Engl J Med,2007,356(3):213-215.
[6]Dulloo AG,Seydoux J,Jacquet J.Adaptive thermogenesis and uncoupling proteins:a reappraisal of their roles in fat metabolism and energy balance[J].Physiol Behav,2004,83(4):587-602.
[7]Lima JJ,Feng H,Duckworth L,et al.Association analyses of adrenergic receptor polymorphisms with obesity and metabolic alterations[J].Metabolism,2007,56(6):757-765.
[8]Chou YC,Tsai CN,Lee YS,et al.Association of adrenergic receptor gene polymorphisms with adolescent obesity in Taiwan[J].Pediatr Int,2012,54(1):111-116.
[9]Park HS,Kim Y,Lee C.Single nucleotide variants in the beta2-adrenergic and beta3-adrenergic receptor genes explained18.3%of adolescent obesity variation[J].J Hum Genet,2005,50(7):365-369.
[10]Dionne IJ,Garant MJ,Nolan AA,et al.Association between obesity and a polymorphism in the beta(1)-adrenoceptor gene(Gly389Arg ADRB1)in Caucasian women[J].Int J Obes Relat Metab Disord,2002,26(5):633-639.
[11]Mottagui-Tabar S,Hoffstedt J,Brookes AJ,et al.Association of ADRB1 and UCP3 gene polymorphisms with insulin sensitivity but not obesity[J].Horm Res,2008,69(1):31-36.
[12]Peng Y,Xue H,Luo L,et al.Polymorphisms of the betaladrenergic receptor gene are associated with essential hypertension in Chinese[J].Clin Chem Lab Med,2009,47(10):1227-1231.
[13]Song YL,Wu XZ,Guo G,et al.[389A/G polymorphism of the human beta l-adrenergic receptor in patients with acute myocardial infarction][J].Zhonghua Yi Xue Yi Chuan Xue Za Zhi,2007,24(4):422-424.
[14]Fragoso JM,Rodriguez-Perez JM,Perez-Vielma N,et al.Betal adrenergic receptor polymorphisms Arg389Gly and Ser49Gly in the Amerindian and Mestizo populations of Mexico[J].Hum Biol,2005,77(4):515-520.
[15]Li S,Chen W,Srinivasan SR,et al.Influence of lipoprotein lipase gene Ser447Stop and beta1-adrenergic receptor gene Arg389Gly polymorphisms and their interaction on obesity from childhood to adulthood:the Bogalusa Heart Study[J].IntJ Obes(Lond),2006,30(8):1183-1188.
[16]Gjesing AP,Andersen G,Albrechtsen A,et al.Studies of associations between the Arg389Gly polymorphism of the beta 1-adrenergic receptor gene(ADRB1)and hypertension and obesity in 7677 Danish white subjects[J].Diabet Med,2007,24(4):392-397.
[17]Silver K,Mitchell BD,Walston J,et al.TRP64ARG beta 3-adrenergic receptor and obesity in Mexican Americans[J].Hum Genet,1997,101(3):306-311.
[18]de Luis DA,Aller R,Izaola O,et al.Relation of Trp64Arg polymorphism of beta 3-adrenergic receptor gene to adipocytokines and fat distribution in obese patients[J].Ann Nutr Metab,2008,52(4):267-271.
[19]Widen E,Lehto M,Kanninen T,et al.Association of a polymorphism in the beta 3-adrenergic-receptor gene with features of the insulin resistance syndrome in Finns[J].N Engl J Med,1995,333(6):348-351.
[20]Oeveren van-Dybicz AM,Vonkeman HE,Bon MA,et al.Beta3-adrenergic receptor gene polymorphism and type 2 diabetes in a Caucasian population[J].Diabetes Obes Metab,2001,3(1):47-51.
[21]Oizumi T,Daimon M,Saitoh T,et al.,and the Funagata Diabetes Study.Genotype Arg/Arg,but not Trp/Arg,of the Trp64Arg polymorphism of the beta(3)-adrenergic receptor is associated with type 2 diabetes and obesity in a large Japanese sample[J].Diabetes Care,2001,24(9):1579-1583.
[22]Tamaki S,Nakamura Y,Tabara Y,et al.Relationship between metabolic syndrome and Trp64arg polymorphism of the betaadrenergic receptor gene in a general sample:the Shigaraki study[J].Hypertens Res,2006,29(11):891-896.
[23]Ogden CL,Kuczmarski RJ,Flegal KM,et al.Centers for Disease Control and Prevention 2000 growth charts for the United States:improvements to the 1977 National Center for Health Statistics version[J].Pediatrics,2002,109(1):45-60.
[24]Matthews DR,Hosker JP.Rudenski As,et al.Homoeostasis model assessment:insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man[J].Diabetologia,1985,28:412-419.
[25]Rodriguez-Moran M,Guerrero-Romero F,Aradillas-Garcia C,et al.Obesity and family history of diabetes as risk factors of impaired fasting glucose:implications for the early detection of prediabetes[J].Pediatr Diabetes,2010,11(5):331-336.
[26]Tafel J,Branscheid I,Skwarna B,et al.Variants in the human beta 1-,beta 2-,and beta 3-adrenergic receptor genes are not associated with morbid obesity in children and adolescents[J].Diabetes Obes Metab,2004,6(6):452-455.
[27]Xie HG,Dishy V,Sofowora G,et al.Arg389Gly beta 1-adrenoceptor polymorphism varies in frequency among different ethnic groups but does not alter response in vivo[J].Pharmacogenetics,2001,11(3):191-197.
[28]Rasmussen M,Belza A,Almdal T,et al.Change in betaladrenergic receptor protein concentration in adipose tissue correlates with diet-induced weight loss[J].Clin Sci(Lond),2005,108(4):323-329.
[29]Mason DA,Moore JD,Green SA,et al.A gain-of-function polymorphism in a G-protein coupling domain of the human beta 1-adrenergic receptor[J].J Biol Chem,1999,274(18):12670-12674.
[30]Zawodniak-Sza apska M,Stawerska R,Brzezianska E,et al.Association of Trp64Arg polymorphism of beta3-adrenergic receptor with insulin resistance in Polish children with obesity[J].J Pediatr Endocrinol Metab,2008,21(2):147-154.
[31]Kurokawa N,Nakai K,Kameo S,et al.Relationship between the beta3-adrenoceptor gene variant and body fat in Japanese children[J].Tohoku J Exp Med,2003,201(4):271-276.
[32]Kurokawa N,Nakai K,Kameo S,et al.Association of BMI with the beta3-adrenergic receptor gene polymorphism in Japanese:meta-analysis[J].Obes Res,2001,9(12):741-745.
[33]Yamakita M,Ando D,Tang S,et al.The Trp64Arg polymorphism of the beta3-adrenergic receptor gene is associated with weight changes in obese Japanese men:a 4-year follow-up study[J].J Physiol Anthropol,2010,29(4):133-139.
[34]Zhu LY,Hu LY,Li XL,et al.Relationship between Trp64Arg mutation in theβ3-adrenergic receptor gene and metabolic syndrome:a seven-year follow-up study[J].Chin Med J(Engl),2010,123(17):2375-2378.
[35]Kasznicki J,Blasiak J,Majsterek I,et al.The Trp64Arg beta3-adrenergic receptor amino-acid variant is not associated with overweight and type 2 diabetes mellitus in Polish population[J].Exp Clin Endocrinol Diabetes,2005,113(10):593-597.
[36]Biery AJ,Ebbesson SO,Shuldiner AR,et al.The beta--adrenergic receptor TRP64ARG polymorphism and obesity in Alaskan Eskimos[J].Int J Obes Relat Metab Disord,1997,21(12):1176-1179.
[37]Lowe WL Jr,Rotimi CN,Luke A,et al.The beta 3-adrenergic receptor gene and obesity in a population sample of African Americans[J].Int J Obes Relat Metab Disord,2001,25(1):54-60.
[38]Kurokawa N,Young EH,Oka Y,et al.The ADRB3 Trp64Arg variant and BMI:a meta-analysis of 44 833 individuals[J].Int J Obes(Land),2008,32(8):1240-1249.
[39]Martinez-Fierro ML,Beuten J,Leach RJ,et al.Ancestry informative markers and admixture proportions in northeastern Mexico[J].J Hum Genet,2009,54(9):504-509.
[40]Kumar S,Mishra A,Srivastava A,et al.Significant role of ADRB3 rs4994 towards the development of coronary artery disease[J].Coron Artery Dis,2014,25(1):29-34.
[41]Anthony EG,Richard E,Lipkowitz MS,et al.Association of the ADRB2(rs2053044)polymorphism and angiotensinconverting enzyme-inhibitor blood pressure response in the African American Study of Kidney Disease and Hypertension[J].Pharmacogenet Genomics,2015,25(9):444-449.