title: Endothelin Type A Receptor Genotype is a Determinant of Quantitative Traits of Metabolic Syndrome in Asian Hypertensive Families: A SAPPHIRe Study.
abstract: Co-heritability of hypertension and insulin resistance (IR) within families not only implies genetic susceptibility may be responsible for these complex traits but also suggests a rational that biological candidate genes for hypertension may serve as markers for features of the metabolic syndrome (MetS). Thus we determined whether the T323C polymorphism (rs5333) of endothelin type A (ETA) receptor, a predominant receptor evoking potent vasoconstrictive action of endothelin-1, contributes to susceptibility to IR-associated hypertension in 1694 subjects of Chinese and Japanese origins. Blood pressures (BPs) and biochemistries were measured. Fasting insulin level, insulin-resistance homeostasis model assessment (HOMAIR) score, and area under curve of insulin concentration (AUCINS) were selected for assessing insulin sensitivity. Genotypes were obtained by methods of polymerase chain reaction-restriction fragment length polymorphism. Foremost findings were that minor allele frequency of the T323C polymorphism was noticeable lower in our overall Asian subjects compared to multi-national population reported in gene database; moreover both the genotypic and allelic frequencies of the polymorphism were significantly different between the two ethnic groups we studied. The genotype distributions at TT/TC/CC were 65, 31, 4% in Chinese and 51, 41, 8% in Japanese, respectively (p < 0.0001). Additionally, carriers of the C homozygote revealed characteristics of IR, namely significantly higher levels of fasting insulin, HOMAIR score, and AUCINS at 29.3, 35.3, and 39.3%, respectively, when compared to their counterparts with TT/TC genotypes in Chinese. Meanwhile, the CC genotype was associated with a higher level of high density lipoprotein cholesterol in Japanese. No association of the polymorphism with BP was observed. This study demonstrated for the first time that T323C polymorphism of ETA receptor gene was associated with an adverse insulin response in Chinese and a favorite atherogenic index in Japanese.
authors.affiliation: Department of Medical Research and Education, Taipei Veterans General Hospital , Taipei , Taiwan ; School of Medicine, National Yang-Ming University , Taipei , Taiwan ; Faculty of Medicine, National Yang-Ming University , Taipei , Taiwan ; Institute of Physiology, National Yang-Ming University , Taipei , Taiwan ; Institute of Clinical Medicine, National Yang-Ming University , Taipei , Taiwan.
authors.forename: Low-Tone
authors.initials: LT
authors.lastname: Ho
authors.affiliation: Department of Medical Research and Education, Taipei Veterans General Hospital , Taipei , Taiwan.
authors.forename: Yung-Pei
authors.initials: YP
authors.lastname: Hsu
authors.affiliation: Division of Biostatistics and Bioinformatics, National Health Research Institutes , Taipei , Taiwan.
authors.forename: Chin-Fu
authors.initials: CF
authors.lastname: Hsiao
authors.affiliation: Cardiovascular Center, Taichung Veterans General Hospital , Taichung , Taiwan.
authors.forename: Chih-Tai
authors.initials: CT
authors.lastname: Ting
authors.affiliation: Division of Endocrinology and Metabolism, Tri-Service General Hospital , Taipei , Taiwan.
authors.forename: Kuang-Chung
authors.initials: KC
authors.lastname: Shih
authors.affiliation: Department of Internal Medicine, National Taiwan University Hospital , Taipei , Taiwan ; Graduate Institute of Clinical Medicine, National Taiwan University , Taipei , Taiwan.
authors.forename: Lee-Ming
authors.initials: LM
authors.lastname: Chuang
authors.affiliation: Kuakini Medical Center , Honolulu , Hawaii.
authors.forename: Kamal
authors.initials: K
authors.lastname: Masaki
authors.affiliation: Department of Public Health Sciences and Epidemiology, John A. Burns School of Medicine, University of Hawaii and Pacific Health Research Institute , Honolulu , Hawaii.
authors.forename: John
authors.initials: J
authors.lastname: Grove
authors.affiliation: Division of Cardiovascular Medicine, Falk Cardiovascular Research Center, Stanford University , Stanford, CA , USA.
authors.forename: Thomas
authors.initials: T
authors.lastname: Quertermous
authors.affiliation: Department of Medical Research and Education, Taipei Veterans General Hospital , Taipei , Taiwan ; Institute of Physiology, National Yang-Ming University , Taipei , Taiwan ; Institute of Clinical Medicine, National Yang-Ming University , Taipei , Taiwan.
authors.forename: Chi-Chung
authors.initials: CC
authors.lastname: Juan
authors.affiliation: Department of Medical Research and Education, Taipei Veterans General Hospital , Taipei , Taiwan ; Faculty of Medicine, National Yang-Ming University , Taipei , Taiwan.
authors.forename: Ming-Wei
authors.initials: MW
authors.lastname: Lin
authors.affiliation: Information Service Center, Taipei Veterans General Hospital , Taipei , Taiwan.
authors.forename: Shu-Chiung
authors.initials: SC
authors.lastname: Chiang
authors.affiliation: Medical Genetics Institute, Cedars-Sinai Medical Center, University of California at Los Angeles , Los Angeles, CA , USA.
authors.forename: Yii-Der I
authors.initials: YD
authors.lastname: Chen
keywords: ETA receptor; T323C polymorphism; hypertension; metabolic syndrome