A common genetic variant of the chromogranin A-derived peptide catestatin is associated with atherogenesis and hypertension in a Japanese population

Youngju Choi; Masahiro Miura; Yoshio Nakata; Takehito Sugasawa; Sumiko Nissato; Takeshi Otsuki; Jun Sugawara; Motoyuki Iemitsu; Yasushi Kawakami; Hitoshi Shimano; Yoshimi Iijima; Kiyoji Tanaka; Shinya Kuno; Prasanna K. R. Allu; Nitish R. Mahapatra; Seiji Maeda; Kazuhiro Takekoshi

doi:10.1507/endocrj.EJ14-0471

ORIGINALS

A common genetic variant of the chromogranin A-derived peptide catestatin is associated with atherogenesis and hypertension in a Japanese population

Youngju Choi, Masahiro Miura, Yoshio Nakata, Takehito Sugasawa, Sumiko Nissato, Takeshi Otsuki, Jun Sugawara, Motoyuki Iemitsu, Yasushi Kawakami, Hitoshi Shimano, Yoshimi Iijima, Kiyoji Tanaka, Shinya Kuno, Prasanna K. R. Allu, Nitish R. Mahapatra, Seiji Maeda, Kazuhiro Takekoshi

Author information

Youngju Choi
Division of Sports Medicine, Faculty of Health and Sport Sciences, University of Tsukuba, Tsukuba 305-8574, Japan
Masahiro Miura
Department of Laboratory Medicine, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba 305-8575, Japan
Yoshio Nakata
Faculty of Medicine, Division of Sports Medicine, University of Tsukuba, Tsukuba 305-8575, Japan
Takehito Sugasawa
Division of Sports Medicine, Faculty of Health and Sport Sciences, University of Tsukuba, Tsukuba 305-8574, Japan
Sumiko Nissato
Department of Laboratory Medicine, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba 305-8575, Japan
Takeshi Otsuki
Faculty of Sport and Health Sciences, Ryutsu Keizai University, Ryugasaki 301-8555, Japan
Jun Sugawara
Human Technology Research Institute, National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba 305-8566, Japan
Motoyuki Iemitsu
Faculty of Sport and Health Science, Ritsumeikan University, Kusatsu 525-8577, Japan
Yasushi Kawakami
Department of Laboratory Medicine, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba 305-8575, Japan
Hitoshi Shimano
Department of Endocrinology and Metabolism, University of Tsukuba, Tsukuba 305-8575, Japan
Yoshimi Iijima
Department of Medical Genetics, Faculty of Medicine, University of Tsukuba, Tsukuba 305-8575, Japan
Kiyoji Tanaka
Division of Sports Medicine, Faculty of Health and Sport Sciences, University of Tsukuba, Tsukuba 305-8574, Japan
Shinya Kuno
Division of Sports Medicine, Faculty of Health and Sport Sciences, University of Tsukuba, Tsukuba 305-8574, Japan
Prasanna K. R. Allu
Department of Biotechnology, Indian Institute of Technology Madras, Chennai-600036, India
Nitish R. Mahapatra
Department of Biotechnology, Indian Institute of Technology Madras, Chennai-600036, India
Seiji Maeda
Division of Sports Medicine, Faculty of Health and Sport Sciences, University of Tsukuba, Tsukuba 305-8574, Japan
Kazuhiro Takekoshi
Faculty of Medicine, Division of Sports Medicine, University of Tsukuba, Tsukuba 305-8575, Japan

Keywords: Catestatin, Pancreastatin, Arterial stiffness, Blood pressure, Japanese

JOURNAL FREE ACCESS

2015 Volume 62 Issue 9 Pages 797-804

DOI https://doi.org/10.1507/endocrj.EJ14-0471

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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.

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