title: A common genetic variant of the chromogranin A-derived peptide catestatin is associated with atherogenesis and hypertension in a Japanese population.
abstract: Chromogranin A (CHGA) is a major protein in the secretory granules of chromaffin cells. CHGA also gives rise to cardiovascular/metabolism regulatory peptides, such as catestatin (CST) and pancreastatin (PST). While CST is a potent inhibitor of catecholamine secretion, PST is a potent physiological inhibitor of glucose-induced insulin secretion. Recently, several SNPs were identified in the CST and PST domains of CHGA locus in different populations. Among the discovered SNPs, CST variant allele Ser-364 was associated with blood pressure alteration and PST variant allele Ser-297 was associated with significantly higher plasma glucose level. In this study, we examined whether these CST and PST variant alleles exist and influence cardiovascular and metabolic phenotypes in Japanese population. Our study comprised of 343 Japanese subjects aged 45-85 years (143 men and 200 women, mean age 66 ± 8 years). We determined the genotypes of CST and PST by PCR-direct sequencing method and carried out genotype-phenotype association analysis. In 343 participants, the minor allele frequency of CST variant Ser-364 was 6.10%. On the other hand, we did not detect the PST variant Ser-297 in this entire study population. The presence of Ser-364 allele was associated with increased in baPWV (an index of systemic arterial stiffness) that suggests an initiation and/or progression atherogenesis and hypertension. The Ser-364 allele was also associated with elevated systolic blood pressure and pulse pressure, consistent with increased baPWV. In conclusion, the CST Ser-364 allele may increase the risk for cardiovascular diseases in Japanese population.
authors.affiliation: Division of Sports Medicine, Faculty of Health and Sport Sciences, University of Tsukuba, Tsukuba 305-8574, Japan.
authors.forename: Youngju
authors.initials: Y
authors.lastname: Choi
authors.forename: Masahiro
authors.initials: M
authors.lastname: Miura
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Nakata
authors.forename: Takehito
authors.initials: T
authors.lastname: Sugasawa
authors.forename: Sumiko
authors.initials: S
authors.lastname: Nissato
authors.forename: Takeshi
authors.initials: T
authors.lastname: Otsuki
authors.forename: Jun
authors.initials: J
authors.lastname: Sugawara
authors.forename: Motoyuki
authors.initials: M
authors.lastname: Iemitsu
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Kawakami
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Shimano
authors.forename: Yoshimi
authors.initials: Y
authors.lastname: Iijima
authors.forename: Kiyoji
authors.initials: K
authors.lastname: Tanaka
authors.forename: Shinya
authors.initials: S
authors.lastname: Kuno
authors.forename: Prasanna K R
authors.initials: PK
authors.lastname: Allu
authors.forename: Nitish R
authors.initials: NR
authors.lastname: Mahapatra
authors.forename: Seiji
authors.initials: S
authors.lastname: Maeda
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Takekoshi
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D050197:Atherosclerosis / Q000235:genetics*; D001794:Blood Pressure / Q000235:genetics*; D053379:Chromogranin A / Q000235:genetics*; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D006973:Hypertension / Q000235:genetics*; D007564:Japan; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide
chemical_list: D053379:Chromogranin A; D010446:Peptide Fragments; C109084:chromogranin A (344-364)