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4. Linkage disequilibrium analyses of natriuretic peptide precursor B locus reveal risk haplotype conferring high plasma BNP levels

Author

Takeishi, Yasuchika, Toriyama, Sayumi, Takabatake, Noriaki, Shibata, Yoko, Konta, Tsuneo, Emi, Mitsuru, Kato, Takeo, Kawata, Sumio, and Kubota, Isao

Subjects
Japan, Humans, Natriuretic Peptide, Brain, SNP, Middle Aged, Male, NPPB, Polymorphism, Single Nucleotide, Female, Linkage Disequilibrium, 493.23, Analysis of Variance, Aged, Asian Continental Ancestry Group, cardiovascular diseases, Haplotypes, human activities, Gene Frequency, hormones, hormone substitutes, and hormone antagonists, Risk Factors, BNP, Genotype
Abstract

Background: Brain natriuretic peptide (BNP) has been widely used for the diagnosis and prognostic evaluation of chronic heart failure (CHF). In the present study, we performed association study of single nucleotide polymorphisms (SNPs) surrounding the natriuretic peptide precursor B (NPPB) gene with plasma BNP levels in 2970 adult Japanese. Methods and Results: Association analysis between SNPs of the NPPB gene and plasma BNP revealed significant associations of the 8 SNPs surrounding the entire NPPB gene with plasma BNP levels. For instance, as to SNP rs198389 (T-381C), plasma BNP levels among the three genotypic categories, i.e., 2189 homozygous T-allele carriers (BNP 26.4 + 0.6 pg/ml), 697 heterozygous carriers (35.0 + 1.1 pg/ml) and 52 homozygous C-allele carriers (46.0 + 4.1 pg/ml) indicated a co-dominant effect of the minor C-allele on elevating plasma BNP levels (P < 0.0001). Linkage disequilibrium (LD) analysis among the 8 SNPs revealed that the region consisted of two, 5’ major and 3’ minor, LD blocks. Haplotype-based association analysis demonstrated that plasma BNP levels were associated closely with the haplotypes-1 and -2 of the major LD block. Conclusion: These results suggest that genetic variation at the primary locus NPPB gene, represented by definition of risk haplotypes, may be an important determinant of plasma BNP levels.

Published
2007

5. The novel and independent association between single-point SNP of NPHP4 gene and renal function in non-diabetic Japanese population: the Takahata study

Author

Konta, Tsuneo, primary, Takasaki, Satoshi, additional, Ichikawa, Kazunobu, additional, Emi, Mitsuru, additional, Toriyama, Sayumi, additional, Satoh, Hitoshi, additional, Ikeda, Ami, additional, Suzuki, Kazuko, additional, Mashima, Yusuke, additional, Shibata, Yoko, additional, Watanabe, Tetsu, additional, Kato, Takeo, additional, Kawata, Sumio, additional, and Kubota, Isao, additional

Published
2010
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6. Association of the Common Fat Mass and Obesity Associated (FTO) Gene Polymorphism with Obesity in a Japanese Population

Author

KARASAWA, Shigeru, primary, DAIMON, Makoto, additional, SASAKI, Satoshi, additional, TORIYAMA, Sayumi, additional, OIZUMI, Toshihide, additional, SUSA, Shinji, additional, KAMEDA, Wataru, additional, WADA, Kiriko, additional, MURAMATSU, Masaaki, additional, FUKAO, Akira, additional, KUBOTA, Isao, additional, KAWATA, Sumio, additional, KAYAMA, Takamasa, additional, and KATO, Takeo, additional

Published
2010
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7. Association of the Ser326Cys polymorphism in the OGG1 gene with type 2 DM

Author

Daimon, Makoto, primary, Oizumi, Toshihide, additional, Toriyama, Sayumi, additional, Karasawa, Shigeru, additional, Jimbu, Yumi, additional, Wada, Kiriko, additional, Kameda, Wataru, additional, Susa, Shinji, additional, Muramatsu, Masaaki, additional, Kubota, Isao, additional, Kawata, Sumio, additional, and Kato, Takeo, additional

Published
2009
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10. Salt consumption-dependent association of the GNB3 gene polymorphism with type 2 DM

Author

Daimon, Makoto, primary, Sato, Hidenori, additional, Sasaki, Satoshi, additional, Toriyama, Sayumi, additional, Emi, Mitsuru, additional, Muramatsu, Masaaki, additional, Hunt, Steven C., additional, Hopkins, Paul N., additional, Karasawa, Shigeru, additional, Wada, Kiriko, additional, Jimbu, Yumi, additional, Kameda, Wataru, additional, Susa, Shinji, additional, Oizumi, Toshihide, additional, Fukao, Akira, additional, Kubota, Isao, additional, Kawata, Sumio, additional, and Kato, Takeo, additional

Published
2008
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11. Association of the PIK3C2G gene polymorphisms with type 2 DM in a Japanese population

Author

Daimon, Makoto, primary, Sato, Hidenori, additional, Oizumi, Toshihide, additional, Toriyama, Sayumi, additional, Saito, Takafumi, additional, Karasawa, Shigeru, additional, Jimbu, Yumi, additional, Wada, Kiriko, additional, Kameda, Wataru, additional, Susa, Shinji, additional, Yamaguchi, Hiroshi, additional, Emi, Mitsuru, additional, Muramatsu, Masaaki, additional, Kubota, Isao, additional, Kawata, Sumio, additional, and Kato, Takeo, additional

Published
2008
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12. Association of an intronic haplotype of the LIPC gene with hyperalphalipoproteinemia in two independent populations

Author

Iijima, Hiroshi, primary, Emi, Mitsuru, additional, Wada, Manabu, additional, Daimon, Makoto, additional, Toriyama, Sayumi, additional, Koyano, Satoru, additional, Sato, Hidenori, additional, Hopkins, Paul N., additional, Hunt, Steven C., additional, Kubota, Isao, additional, Kawata, Sumio, additional, and Kato, Takeo, additional

Published
2007
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13. Cytoplasmic destruction of p53 by the endoplasmic reticulum-resident ubiquitin ligase ‘Synoviolin’

Author

Yamasaki, Satoshi, primary, Yagishita, Naoko, additional, Sasaki, Takeshi, additional, Nakazawa, Minako, additional, Kato, Yukihiro, additional, Yamadera, Tadayuki, additional, Bae, Eunkyung, additional, Toriyama, Sayumi, additional, Ikeda, Rie, additional, Zhang, Lei, additional, Fujitani, Kazuko, additional, Yoo, Eunkyung, additional, Tsuchimochi, Kaneyuki, additional, Ohta, Tomohiko, additional, Araya, Natsumi, additional, Fujita, Hidetoshi, additional, Aratani, Satoko, additional, Eguchi, Katsumi, additional, Komiya, Setsuro, additional, Maruyama, Ikuro, additional, Higashi, Nobuyo, additional, Sato, Mitsuru, additional, Senoo, Haruki, additional, Ochi, Takahiro, additional, Yokoyama, Shigeyuki, additional, Amano, Tetsuya, additional, Kim, Jaeseob, additional, Gay, Steffen, additional, Fukamizu, Akiyoshi, additional, Nishioka, Kusuki, additional, Tanaka, Keiji, additional, and Nakajima, Toshihiro, additional

Published
2006
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14. A nonfunctioning single nucleotide polymorphism in olfactory receptor gene family is associated with the forced expiratory volume in the first second/the forced vital capacity values of pulmonary function test in a Japanese population

Author

Takabatake, Noriaki, Toriyama, Sayumi, Takeishi, Yasuchika, Shibata, Yoko, Konta, Tsuneo, Inoue, Sumito, Abe, Shuichi, Igarashi, Akira, Tokairin, Yoshikane, Ishii, Miho, Koyano, Satoru, Emi, Mitsuru, Kato, Takeo, Kawata, Sumio, and Kubota, Isao

Subjects
*NUCLEOTIDES, *GENES, *CARDIOPULMONARY system, *PULMONARY function tests
Abstract

Abstract: The forced expiratory volume in the first second (FEV1.0)/the forced vital capacity (FVC) is an important index of a single forced expiration. Ectopic expression of the human olfactory receptor (OR) gene family in the lungs has suggested its potential involvement of respiratory physiology. We hypothesized that the individual variability of FEV1.0/FVC value may be attributed to the genetic variance of the OR gene family caused by the nonfunctioning SNPs (nSNPs). We conducted quantitative trait locus (QTL) analyses of population having the 7 OR gene nSNPs and FEV1.0/FVC values by ANOVA, in 2970 samples in the Yamagata Takahata cohort. We found significant association of one nSNP [rs10838851, OR, family 4, subfamily X, member 1 (OR4X1) gene, Tyr273Ter∗] with FEV1.0/FVC (%) (P =0.008). The FEV1.0/FVC value (%) of population having OR4X1 gene nSNP Ter∗/Ter∗, Ter∗/Tyr, and Tyr/Tyr were 78.9±0.2, 78.2±0.2, and 77.7±0.4, respectively. Haplotype-based analysis of the OR4X1 gene with FEV1.0/FVC values demonstrated that two exclusive haplotypes [Hap-1/Hap-2 (frequency 0.669/0.330): SNP1 (rs7106648)T/A-SNP2 (rs871249)G/A-SNP3 (rs713325)G/A-SNP4 (rs10838851)A (Ter∗)/T (Tyr)-SNP5 (rs4752923)G/A-SNP6 (rs960640)G/A] were significantly associated with FEV1.0/FVC values (global P =0.005). These results suggest that OR4X1 may be one of the genes that contribute to the individual variability of FEV1.0/FVC value in pulmonary function test. [Copyright &y& Elsevier]

Published
2007
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15. Cytoplasmic destruction of p53 by the endoplasmic reticulum-resident ubiquitin ligase ‘Synoviolin’.

Author

Yamasaki, Satoshi, Yagishita, Naoko, Sasak, Takeshi, Nakazawa, Minako, Kato, Yukihiro, Yamadera, Tadayuki, Eunkyung Bae, Toriyama, Sayumi, Ikeda, Rie, Lei Zhang, Fujitani, Kazuko, Yoo, Eunkyung, Tsuchimochi, Kaneyuki, Ohta, Tomohiko, Araya, Natsumi, Fujita, Hidetoshi, Aratani, Satoko, Eguchi, Katsumi, Komiya, Setsuro, and Maruyama, Ikuro

Subjects
UBIQUITIN, LIGASES, ENDOPLASMIC reticulum, EMBRYOLOGY, JOINT diseases, P53 protein, CELL cycle, MAMMALS
Abstract

Synoviolin, also called HRD1, is an E3 ubiquitin ligase and is implicated in endoplasmic reticulum -associated degradation. In mammals, Synoviolin plays crucial roles in various physiological and pathological processes, including embryogenesis and the pathogenesis of arthropathy. However, little is known about the molecular mechanisms of Synoviolin in these actions. To clarify these issues, we analyzed the profile of protein expression in synoviolin-null cells. Here, we report that Synoviolin targets tumor suppressor gene p53 for ubiquitination. Synoviolin sequestrated and metabolized p53 in the cytoplasm and negatively regulated its cellular level and biological functions, including transcription, cell cycle regulation and apoptosis. Furthermore, these p53 regulatory functions of Synoviolin were irrelevant to other E3 ubiquitin ligases for p53, such as MDM2, Pirh2 and Cop1, which form autoregulatory feedback loops. Our results provide novel insights into p53 signaling mediated by Synoviolin. [ABSTRACT FROM AUTHOR]

Published
2007
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