A 192Arg variant of the human paraoxonase (HUMPONA) gene polymorphism is associated with an increased risk for coronary artery disease in the Japanese

Takeru Zama; Mitsuru Murata; Yumiko Matsubara; Koichi Kawano; Nobuo Aoki; Hideaki Yoshino; Gentaro Watanabe; Kyozo Ishikawa; Yasuo Ikeda

doi:10.1161/01.ATV.17.12.3565

A ¹⁹²Arg variant of the human paraoxonase (HUMPONA) gene polymorphism is associated with an increased risk for coronary artery disease in the Japanese

Takeru Zama, Mitsuru Murata, Yumiko Matsubara, Koichi Kawano, Nobuo Aoki, Hideaki Yoshino, Gentaro Watanabe, Kyozo Ishikawa, Yasuo Ikeda

Department of Laboratory Medicine

Research output: Contribution to journal › Article › peer-review

151 Citations (Scopus)

Abstract

Recent reports have suggested that polymorphisms in the human paraoxonase (HUMPONA) gene may be a genetic risk factor for coronary artery disease (CAD) in white populations. However, this association has nor yet been confirmed in other ethnic populations. We studied 75 Japanese patients with CAD, whose coronary lesions were confirmed by angiography, and 115 Japanese control subjects with no history of CAD and a normal resting electrocardiogram. The assays for genotyping the two polymorphisms in the HUMPONA gene (¹⁹²Arg/Gln and ⁵⁵Leu/Met) were based on changes in restriction enzyme digestion patterns. For codon 192, the frequencies of the Arg-coding allele (B allele) in both patients and control subjects were much higher than those from published results of whites (.26 to 131), and the difference between patients (.74) and control subjects (.59) was statistically significant (P=.002). The patient group had a higher proportion of Arg/Arg (B/B) homozygotes (52.0% vs 32.2%, P=.006). For codon 55, the frequencies of the Leu-coding allele in control subjects and pat ants were much higher (.91 and .93, respectively) than those published results for whites, but there was no difference between Japanese control subjects and Japanese patients. When subjects with the ⁵⁵Leu/Leu genotype only were analyzed, ¹⁹²Arg/Arg homozygotes were still significantly more frequent in the patients than in the control subjects (55.4% vs 37.2%, P=.024), and the frequency of the ¹⁹²Arg allele was also higher in patients than control subjects (P=.013). Logistic regress on analysis including conventional coronary risk factors revealed that ¹⁹²Arg is an independent risk factor for CAD. Thus, in the Japanese, the association of CAD with the ¹⁹²Arg variant of HUMPONA (B-type enzyme) is similar to that reported for whites, although the allele frequencies for ¹⁹²Arg and ⁵⁵Leu are much higher in the former than the latter population.

Original language	English
Pages (from-to)	3565-3569
Number of pages	5
Journal	Arteriosclerosis, Thrombosis, and Vascular Biology
Volume	17
Issue number	12
DOIs	https://doi.org/10.1161/01.ATV.17.12.3565
Publication status	Published - 1997

Keywords

Angiography
Coronary artery disease
Genetics
Paraoxonase
Risk factors

ASJC Scopus subject areas

Cardiology and Cardiovascular Medicine

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This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1161/01.ATV.17.12.3565

Cite this

Zama, T., Murata, M., Matsubara, Y., Kawano, K., Aoki, N., Yoshino, H., Watanabe, G., Ishikawa, K., & Ikeda, Y. (1997). A ¹⁹²Arg variant of the human paraoxonase (HUMPONA) gene polymorphism is associated with an increased risk for coronary artery disease in the Japanese. Arteriosclerosis, Thrombosis, and Vascular Biology, 17(12), 3565-3569. https://doi.org/10.1161/01.ATV.17.12.3565

A ¹⁹²Arg variant of the human paraoxonase (HUMPONA) gene polymorphism is associated with an increased risk for coronary artery disease in the Japanese. / Zama, Takeru; Murata, Mitsuru; Matsubara, Yumiko et al.

In: Arteriosclerosis, Thrombosis, and Vascular Biology, Vol. 17, No. 12, 1997, p. 3565-3569.

Research output: Contribution to journal › Article › peer-review

Zama, T, Murata, M, Matsubara, Y, Kawano, K, Aoki, N, Yoshino, H, Watanabe, G, Ishikawa, K & Ikeda, Y 1997, 'A ¹⁹²Arg variant of the human paraoxonase (HUMPONA) gene polymorphism is associated with an increased risk for coronary artery disease in the Japanese', Arteriosclerosis, Thrombosis, and Vascular Biology, vol. 17, no. 12, pp. 3565-3569. https://doi.org/10.1161/01.ATV.17.12.3565

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title = "A 192Arg variant of the human paraoxonase (HUMPONA) gene polymorphism is associated with an increased risk for coronary artery disease in the Japanese",

abstract = "Recent reports have suggested that polymorphisms in the human paraoxonase (HUMPONA) gene may be a genetic risk factor for coronary artery disease (CAD) in white populations. However, this association has nor yet been confirmed in other ethnic populations. We studied 75 Japanese patients with CAD, whose coronary lesions were confirmed by angiography, and 115 Japanese control subjects with no history of CAD and a normal resting electrocardiogram. The assays for genotyping the two polymorphisms in the HUMPONA gene (192Arg/Gln and 55Leu/Met) were based on changes in restriction enzyme digestion patterns. For codon 192, the frequencies of the Arg-coding allele (B allele) in both patients and control subjects were much higher than those from published results of whites (.26 to 131), and the difference between patients (.74) and control subjects (.59) was statistically significant (P=.002). The patient group had a higher proportion of Arg/Arg (B/B) homozygotes (52.0% vs 32.2%, P=.006). For codon 55, the frequencies of the Leu-coding allele in control subjects and pat ants were much higher (.91 and .93, respectively) than those published results for whites, but there was no difference between Japanese control subjects and Japanese patients. When subjects with the 55Leu/Leu genotype only were analyzed, 192Arg/Arg homozygotes were still significantly more frequent in the patients than in the control subjects (55.4% vs 37.2%, P=.024), and the frequency of the 192Arg allele was also higher in patients than control subjects (P=.013). Logistic regress on analysis including conventional coronary risk factors revealed that 192Arg is an independent risk factor for CAD. Thus, in the Japanese, the association of CAD with the 192Arg variant of HUMPONA (B-type enzyme) is similar to that reported for whites, although the allele frequencies for 192Arg and 55Leu are much higher in the former than the latter population.",

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T1 - A 192Arg variant of the human paraoxonase (HUMPONA) gene polymorphism is associated with an increased risk for coronary artery disease in the Japanese

AU - Zama, Takeru

AU - Murata, Mitsuru

AU - Matsubara, Yumiko

AU - Kawano, Koichi

AU - Aoki, Nobuo

AU - Yoshino, Hideaki

AU - Watanabe, Gentaro

AU - Ishikawa, Kyozo

AU - Ikeda, Yasuo

PY - 1997

Y1 - 1997

N2 - Recent reports have suggested that polymorphisms in the human paraoxonase (HUMPONA) gene may be a genetic risk factor for coronary artery disease (CAD) in white populations. However, this association has nor yet been confirmed in other ethnic populations. We studied 75 Japanese patients with CAD, whose coronary lesions were confirmed by angiography, and 115 Japanese control subjects with no history of CAD and a normal resting electrocardiogram. The assays for genotyping the two polymorphisms in the HUMPONA gene (192Arg/Gln and 55Leu/Met) were based on changes in restriction enzyme digestion patterns. For codon 192, the frequencies of the Arg-coding allele (B allele) in both patients and control subjects were much higher than those from published results of whites (.26 to 131), and the difference between patients (.74) and control subjects (.59) was statistically significant (P=.002). The patient group had a higher proportion of Arg/Arg (B/B) homozygotes (52.0% vs 32.2%, P=.006). For codon 55, the frequencies of the Leu-coding allele in control subjects and pat ants were much higher (.91 and .93, respectively) than those published results for whites, but there was no difference between Japanese control subjects and Japanese patients. When subjects with the 55Leu/Leu genotype only were analyzed, 192Arg/Arg homozygotes were still significantly more frequent in the patients than in the control subjects (55.4% vs 37.2%, P=.024), and the frequency of the 192Arg allele was also higher in patients than control subjects (P=.013). Logistic regress on analysis including conventional coronary risk factors revealed that 192Arg is an independent risk factor for CAD. Thus, in the Japanese, the association of CAD with the 192Arg variant of HUMPONA (B-type enzyme) is similar to that reported for whites, although the allele frequencies for 192Arg and 55Leu are much higher in the former than the latter population.

AB - Recent reports have suggested that polymorphisms in the human paraoxonase (HUMPONA) gene may be a genetic risk factor for coronary artery disease (CAD) in white populations. However, this association has nor yet been confirmed in other ethnic populations. We studied 75 Japanese patients with CAD, whose coronary lesions were confirmed by angiography, and 115 Japanese control subjects with no history of CAD and a normal resting electrocardiogram. The assays for genotyping the two polymorphisms in the HUMPONA gene (192Arg/Gln and 55Leu/Met) were based on changes in restriction enzyme digestion patterns. For codon 192, the frequencies of the Arg-coding allele (B allele) in both patients and control subjects were much higher than those from published results of whites (.26 to 131), and the difference between patients (.74) and control subjects (.59) was statistically significant (P=.002). The patient group had a higher proportion of Arg/Arg (B/B) homozygotes (52.0% vs 32.2%, P=.006). For codon 55, the frequencies of the Leu-coding allele in control subjects and pat ants were much higher (.91 and .93, respectively) than those published results for whites, but there was no difference between Japanese control subjects and Japanese patients. When subjects with the 55Leu/Leu genotype only were analyzed, 192Arg/Arg homozygotes were still significantly more frequent in the patients than in the control subjects (55.4% vs 37.2%, P=.024), and the frequency of the 192Arg allele was also higher in patients than control subjects (P=.013). Logistic regress on analysis including conventional coronary risk factors revealed that 192Arg is an independent risk factor for CAD. Thus, in the Japanese, the association of CAD with the 192Arg variant of HUMPONA (B-type enzyme) is similar to that reported for whites, although the allele frequencies for 192Arg and 55Leu are much higher in the former than the latter population.

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KW - Genetics

KW - Paraoxonase

KW - Risk factors

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