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

*この研究の対応する著者

研究成果: Article査読

11 被引用数 (Scopus)

抄録

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.

本文言語English
ページ(範囲)797-804
ページ数8
ジャーナルEndocrine Journal
62
9
DOI
出版ステータスPublished - 2015 9 30
外部発表はい

ASJC Scopus subject areas

  • 内分泌学、糖尿病および代謝内科学
  • 内分泌学

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