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Hirosaki, Japan

Oguri M.,Red Cross | Kato K.,Gifu Prefectural Tajimi Hospital | Yokoi K.,Gifu Prefectural Tajimi Hospital | Yoshida T.,Inabe General Hospital | And 7 more authors.
American Journal of Hypertension | Year: 2010

Background Hypertension is a major risk factor for cardiovascular disease. Although genetic studies have suggested that several genetic variants increase the risk for hypertension, the genes that underlie genetic susceptibility to this condition remain to be identified definitively. The purpose of the present study was to identify genetic variants that confer susceptibility to hypertension in Japanese individuals. Methods A total of 5,734 Japanese individuals from two independent populations were examined: Subject panel A comprised 2,066 hypertensive individuals and 824 controls; and subject panel B comprised 834 hypertensive individuals and 2,010 controls. The 150 polymorphisms examined in the present study were selected by genome-wide association studies of myocardial infarction and ischemic stroke with the use of the GeneChip Human Mapping 500K Array Set (Affymetrix). Results The χ2-test revealed that 10 polymorphisms were significantly (P <0.05) related to the prevalence of hypertension in subject panel A. To validate the relations, these polymorphisms were examined in subject panel B. The A→G polymorphism (rs645106) of SDK1 and the C→G polymorphism (rs12078839) of RABGAP1L were significantly associated with hypertension in subject panel B. Multivariable logistic regression analysis with djustment for covariates, as well as a stepwise forward selection procedure revealed that the A→G polymorphism of SDK1 was significantly associated with hypertension in both subject panels A and B, with the G allele protecting against this condition. Conclusions SDK1 may be a susceptibility gene for hypertension in Japanese individuals, although the functional relevance of the identified polymorphism was not determined. © 2010 American Journal of Hypertension, Ltd. Source


Yoshida T.,Inabe General Hospital | Kato K.,Gifu Prefectural Tajimi Hospital | Yokoi K.,Gifu Prefectural Tajimi Hospital | Oguri M.,Red Cross | And 7 more authors.
Experimental and Therapeutic Medicine | Year: 2010

Hypertension and diabetes mellitus are important risk factors for chronic kidney disease (CKD). The purpose of the present study was to identify genetic variants that confer susceptibility to CKD in individuals with or without hypertension or diabetes mellitus, thereby contributing to the personalized prevention of CKD in such individuals separately. The study population comprised 5835 unrelated Japanese individuals, including 1763 subjects with CKD and 4072 controls. The 150 polymorphisms were selected by genome-wide association studies of ischemic stroke and myocardial infarction with the use of the Gene chip human mapping 500K array Set (affymetrix). The genotypes for these polymorphisms were determined by a method that combines polymerase chain reaction and sequence-specific oligo nucleotide probes with suspension array technology. the χ2 test, multivariable logistic regression analysis with adjustment for covariates, as well as a stepwise forward selection procedure revealed that two different polymorphisms were significantly (P<0.005) associated with the prevalence of CKD in individuals with or without hypertension or diabetes mellitus: the a→G (lys625arg) polymorphism of CDH4 (rs6142884) in individuals without diabetes mellitus, and the c→t polymorphism of PTPRN2 (rs1638021) in individuals with hypertension and diabetes mellitus. No polymorphism. Source


Yoshida T.,Inabe General Hospital | Kato K.,Gifu Prefectural Tajimi Hospital | Yokoi K.,Gifu Prefectural Tajimi Hospital | Oguri M.,Red Cross | And 7 more authors.
International Journal of Molecular Medicine | Year: 2010

Dyslipidemia is an important risk factor for myocardial infarction (MI). We previously showed that gene polymorphisms associated with MI differed among individuals with different lipid profiles. We further examined whether genetic variants that confer susceptibility to MI might differ among individuals with low or high serum concentrations of triglycerides, high density lipoprotein (HDL)-cholesterol, or low density lipoprotein (LDL)-cholesterol. The study population comprised 5270 Japanese individuals, including 1188 subjects with MI and 4082 controls. The 150 polymorphisms examined in the present study were selected by genome-wide association studies of MI and ischemic stroke with the use of the Affymetrix GeneChip Human Mapping 500K Array Set. The initial Chi-square test revealed that the A→G polymorphism (rs12632110) of SEMA3F was significantly (false discovery rate <0.05) associated with MI among individuals with high serum HDL-cholesterol or among those with low serum LDL-cholesterol. Subsequent multivariable logistic regression analysis with adjustment for covariates revealed that rs12632110 was significantly (P<0.01) associated with MI in individuals with high serum HDL-cholesterol or with low serum LDL-cholesterol. The genetic variants that confer susceptibility to MI differ among individuals with different lipid profiles, and the genetic component for the development of MI is more apparent in individuals at low-risk (high HDL- and low LDL-cholesterol levels) compared to those at high-risk. Stratification of subjects according to lipid profiles may thus be important for personalized prevention of MI based on genetic information. Source


Fujimaki T.,Gifu Prefectural Tajimi Hospital | Kato K.,Gifu Prefectural Tajimi Hospital | Yokoi K.,Gifu Prefectural Tajimi Hospital | Oguri M.,Red Cross | And 9 more authors.
Atherosclerosis | Year: 2010

Objective: The purpose of the present study was to identify genetic variants that confer susceptibility to myocardial infarction (MI) in Japanese individuals. Methods: The study population comprised 5014 Japanese individuals, including 1444 subjects with MI and 3570 controls. The 150 polymorphisms examined in the present study were selected by a genome-wide association study for ischemic stroke with the use of the GeneChip Human Mapping 500K Array Set (Affymetrix), and were determined by a method that combines the polymerase chain reaction and sequence-specific oligonucleotide probes with suspension array technology. Results: An initial screen by the chi-square test revealed that the A→G polymorphism of SEMA3F (rs12632110), the C→T polymorphism of CLEC16A (rs9925481), the A→G polymorphism of LAMA3 (rs12373237), and the C→G polymorphism of PCSK2 (rs6080699) were significantly (false discovery rate for allele frequencies of <0.05) associated with MI. Subsequent multivariable logistic regression analysis with adjustment for covariates and a stepwise forward selection procedure revealed that the A→G polymorphism of SEMA3F (dominant model; P= 0.0014; odds ratio, 0.76), the C→T polymorphism of CLEC16A (dominant model; P= 0.0009; odds ratio, 0.75), the A→G polymorphism of LAMA3 (recessive model; P= 0.0099; odds ratio, 0.80), and the C→G polymorphism of PCSK2 (recessive model; P= 0.0155; odds ratio, 1.19) were significantly (P<. 0.05) associated with the prevalence of MI. Conclusion: Determination of these genotypes may prove informative for assessment of the genetic risk for MI in Japanese individuals. © 2009 Elsevier Ireland Ltd. Source


Fujimaki T.,Gifu Prefectural Tajimi Hospital | Kato K.,Gifu Prefectural Tajimi Hospital | Yokoi K.,Gifu Prefectural Tajimi Hospital | Yoshida T.,Inabe General Hospital | And 8 more authors.
International Journal of Molecular Medicine | Year: 2010

Although chronic kidney disease (CKD) is recognized as an important risk factor for myocardial infarction (MI), genetic factors underlying predisposition to MI in individuals with or without CKD remain largely unknown. The aim of the present study was to identify genetic variants that confer susceptibility to MI in individuals with or without CKD in order to allow prediction of genetic risk for such individuals separately. The study population comprised a total of 4344 individuals, including 1247 individuals with CKD (506 subjects with MI and 741 controls) and 3097 individuals without CKD (833 subjects with MI and 2264 controls). The 150 polymorphisms examined in this study were selected by genome-wide association studies of ischemic stroke and MI with the use of the GeneChip Human Mapping 500K Array Set (Affymetrix) and determined by a method that combines the polymerase chain reaction and sequencespecific oligonucleotide probes with suspension array technology. In individuals with CKD, no polymorphism was significantly related to MI. In individuals without CKD, an initial screen by the Chi-square test revealed that the C→T polymorphism of CLEC16A (rs9925481) and the A→G polymorphism of LAMA3 (rs12373237) were significantly (false discovery rate for allele frequencies of <0.05) associated with MI. Subsequent multivariable logistic regression analysis with adjustment for covariates revealed that the C→T polymorphism of CLEC16A (dominant model; P=0.0003; odds ratio, 0.66) and the A→G polymorphism of LAMA3 (recessive model; P=0.0087; odds ratio, 0.75) were significantly (P<0.05) associated with MI. A stepwise forward selection procedure also revealed that these polymorphisms were significant and independent determinants of MI. CLEC16A and LAMA3 may be susceptibility loci for MI in Japanese individuals without CKD. Determination of genotypes for CLEC16A and LAMA3 may prove informative for assessment of the genetic risk for MI in such individuals. Source

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