title: Variation in genes that regulate blood pressure are associated with glomerular filtration rate in Chinese.
abstract: Chronic kidney disease (CKD) can be a consequence of diabetes, hypertension, immunologic disorders, and other exposures, as well as genetic factors that are still largely unknown. Glomerular filtration rate (GFR), which is widely used to measure kidney function, has a heritability ranging from 25% to 75%, but only 1.5% of this heritability is explained by genetic loci that have been identified to date. In this study we tested for associations between GFR and 234 SNPs in 26 genes from pathways of blood pressure regulation in 3,025 rural Chinese participants of the "Genetic Epidemiology Network of Salt Sensitivity" (GenSalt) study. We estimated GFR (eGFR) using baseline serum creatinine measurements obtained prior to dietary intervention. We identified significant associations between eGFR and 12 SNPs in 6 genes (ACE, ADD1, AGT, GRK4, HSD11B1, and SCNN1G). The cumulative effect of the protective alleles was an increase in mean eGFR of 4 mL/min per 1.73 m2, while the cumulative effect of the risk alleles was a decrease in mean eGFR of 3 mL/min per 1.73 m2. In addition, we identified a significant interaction between SNPs in CYP11B1 and ADRB2. We have identified common variants in genes from pathways that regulate blood pressure and influence kidney function as measured by eGFR, providing new insights into the genetic determinants of kidney function. Complex genetic effects on kidney function likely involve interactions among genes as we observed for CYP11B1 and ADRB2.
authors.affiliation: Human Genetics Center, School of Public Health, University of Texas Health Science Center at Houston, Houston, Texas, United States of America.
authors.forename: May E
authors.initials: ME
authors.lastname: Montasser
authors.affiliation: Human Genetics Center, School of Public Health, University of Texas Health Science Center at Houston, Houston, Texas, United States of America.
authors.forename: Lawrence C
authors.initials: LC
authors.lastname: Shimmin
authors.affiliation: Cardiovascular Institute and Fu Wai Hospital, Chinese Academy of Medical Sciences, Beijing, China.
authors.forename: Dongfeng
authors.initials: D
authors.lastname: Gu
authors.affiliation: Tulane University School of Medicine, New Orleans, Louisiana, United States of America.
authors.forename: Jing
authors.initials: J
authors.lastname: Chen
authors.affiliation: Washington University in School of Medicine, St. Louis, Missouri, United States of America.
authors.forename: Charles
authors.initials: C
authors.lastname: Gu
authors.affiliation: Tulane University School of Public Health and Tropical Medicine, New Orleans, Louisiana, United States of America.
authors.forename: Tanika N
authors.initials: TN
authors.lastname: Kelly
authors.affiliation: National Heart, Lung and Blood Institute, National Institute of Health, Bethesda, Maryland, United States of America.
authors.forename: Cashell E
authors.initials: CE
authors.lastname: Jaquish
authors.affiliation: Washington University in School of Medicine, St. Louis, Missouri, United States of America.
authors.forename: Treva K
authors.initials: TK
authors.lastname: Rice
authors.affiliation: Washington University in School of Medicine, St. Louis, Missouri, United States of America.
authors.forename: Dabeeru C
authors.initials: DC
authors.lastname: Rao
authors.affiliation: Cardiovascular Institute and Fu Wai Hospital, Chinese Academy of Medical Sciences, Beijing, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Cao
authors.affiliation: Cardiovascular Institute and Fu Wai Hospital, Chinese Academy of Medical Sciences, Beijing, China.
authors.forename: Jichun
authors.initials: J
authors.lastname: Chen
authors.affiliation: National Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Beijing, China.
authors.lastname: De-PeLiu
authors.affiliation: Tulane University School of Public Health and Tropical Medicine, New Orleans, Louisiana, United States of America.
authors.forename: Paul K
authors.initials: PK
authors.lastname: Whelton
authors.affiliation: Tulane University School of Medicine, New Orleans, Louisiana, United States of America.
authors.forename: Lotuce Lee
authors.initials: LL
authors.lastname: Hamm
authors.affiliation: Tulane University School of Public Health and Tropical Medicine, New Orleans, Louisiana, United States of America.
authors.forename: Jiang
authors.initials: J
authors.lastname: He
authors.affiliation: Human Genetics Center, School of Public Health, University of Texas Health Science Center at Houston, Houston, Texas, United States of America.
authors.forename: James E
authors.initials: JE
authors.lastname: Hixson
mesh_terms: D000293:Adolescent; D000328:Adult; D044466:Asian People / Q000235:genetics; D001794:Blood Pressure / Q000235:genetics*; D005796:Genes; D005919:Glomerular Filtration Rate / Q000235:genetics*; D006801:Humans; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D018343:Receptors, Adrenergic, beta-2 / Q000235:genetics; D013252:Steroid 11-beta-Hydroxylase / Q000235:genetics
chemical_list: C553443:ADRB2 protein, human; D018343:Receptors, Adrenergic, beta-2; D013252:Steroid 11-beta-Hydroxylase