Genotype frequencies for polymorphisms related to chemotherapy-induced nausea and vomiting in a Japanese population.

BACKGROUND: Genotype frequencies for chemotherapy-induced nausea and vomiting (CINV)-related polymorphisms have not yet been reported for Japanese subjects. METHODS: We analyzed 10 genotype frequencies for following polymorphisms associated with the development of CINV: serotonin 5-HT3 receptors (HTR3); neurokinin-1 receptors (Tachykinin-1 receptors, TACR1); dopamine D2 receptors (DRD2); and catechol-O-methyltransferase (COMT). RESULTS: All polymorphisms were successfully genotyped in 200 Japanese subjects and were in Hardy-Weinberg equilibrium. Almost all genotype frequencies were similar to those in the HapMap database or in the previous reports, while frequencies for the Y192H polymorphism in TACR1 were different in Japanese subjects from those in a previous report. CONCLUSIONS: The present study revealed genotype frequencies for polymorphisms, which were related to the appearance of CINV in Japanese subjects. Individual therapy based on genotype variations for each race is needed to allow cancer patients to undergo chemotherapy more safely and to understand etiology of CINV.

Polymorphisms of Nrf2, an antioxidative gene, are associated with blood pressure in Japanese.

Nuclear factor-erythroid 2 (NF-E2)-related factor 2 (Nrf2) is a transcription factor that regulates the expression of antioxidant genes by activating Nrf2-antioxidant response element (ARE) pathway. This study aimed to investigate association of Nrf2 gene single nucleotide polymorphisms (SNPs), rs35652124 (A --> G) and rs6721961 (C --> A), with various laboratory data in 464 health evaluation examinees. The genotyping of these SNPs was performed using polymerase chain reaction with confronting two-pair primers (PCR-CTPP) assay. The genotype frequencies of rs35652124 SNP were 21.1% for AA, 44.0% for AG, and 34.9% for GG. The frequency of A allele was 0.431. In male subjects, cholinesterase was significantly high, and HDL cholesterol was significantly low in (AG+GG) carriers. In female subjects, diastolic blood pressure (BP) was significantly low in (AG+GG) carriers. The genotype frequencies of rs6721961 SNP were 55.2% for CC, 34.7% for CA, and 10.1% for AA. The frequency of A allele was 0.275. In male subjects, systolic BP, diastolic BP and cholinesterase were significantly low, and iron was significantly high in (CA+AA) carriers. In female subjects, cholinesterase was significantly high in (CA+AA) carriers, and diastolic BP was significantly high in AA carriers. In conclusion, Nrf2 polymorphisms are associated with BP in Japanese.

Polymorphism of Nrf2, an antioxidative gene, is associated with blood pressure and cardiovascular mortality in hemodialysis patients.

OBJECTIVE: Nrf2 is a transcription factor that regulates the expression of antioxidant genes. This study aimed to investigate the association of Nrf2 gene single nucleotide polymorphisms (SNPs), rs35652124 (-653A/G) and rs6721961 (-617C/A), with laboratory data and mortality in hemodialysis (HD) patients. METHODS: Blood samples were obtained from 216 HD patients (119 males and 97 females; 60 diabetics and 156 non-diabetics) with mean age of 60.3±13.3 (SD) years, and mean HD duration of 9.10±8.28 years. Genotyping was performed using polymerase chain reaction with confronting two-pair primers (PCR-CTPP) assay. RESULTS: As for rs35652124, diastolic blood pressure (BP) was significantly high in total AA carriers. ß2-microglobulin was significantly low in male AA carriers. Systolic BP, diastolic BP and albumin were significantly high in female AA carriers. As for 6721961, systolic BP and diastolic BP were significantly high in female AA carriers. Cox proportional hazard analysis adjusted for age, HD duration, diabetes and Kt/V demonstrated that rs35652124 AA carriers showed higher cardiovascular mortality than (GG+GA) carriers. CONCLUSION: Nrf2 SNPs were associated with BP in Japanese HD patients. More notably, rs35652124 was associated with cardiovascular mortality in these patients.

SIRTUIN 1 gene polymorphisms are associated with cholesterol metabolism and coronary artery calcification in Japanese hemodialysis patients.

OBJECTIVES: Sirtuin 1 (SIRT1), a longevity gene, protects cells against oxidative and genotoxic stress. This study aimed to investigate the association of SIRT 1 gene single-nucleotide polymorphisms, namely, rs7895833, rs7069102, and rs2273773 with lipid profiles and coronary artery calcification score in 219 Japanese hemodialysis (HD) patients. METHODS: Genotyping of these polymorphisms was performed using polymerase chain reaction with confronting two-pair primers assay. RESULTS: The A allele frequency of rs7895833 and G allele frequency of rs7069102 were significantly lower in HD patients (0.228 and 0.131, respectively) than those in 803 control subjects (general population) (0.289 and 0.181, respectively) (P = .010 and P = .012, respectively). However, the allele frequency of rs2273773 was not significantly different from that in the control subjects. Multivariate analysis adjusted for age and duration on HD demonstrated that the serum levels of total and low-density lipoprotein cholesterol were significantly high in G allele carriers of rs7069102 compared with CC genotype in male HD patients. Coronary artery calcification score was significantly high in C allele carriers of rs2273773 in all and male HD patients. CONCLUSIONS: SIRT 1 polymorphisms, rs7069102 and rs2273773, are associated with abnormal cholesterol metabolism and coronary artery calcification, respectively, in Japanese HD patients, especially in males.

Coronary artery calcification score is associated with mortality in Japanese hemodialysis patients.

OBJECTIVE: Coronary artery calcification has been associated with higher mortality in coronary artery disease and chronic kidney disease. This study aimed to correlate coronary artery calcification score (CACS) with all-cause and cardiovascular mortalities in hemodialysis (HD) patients. DESIGN, SETTING, SUBJECTS: A survival analysis was conducted in 200 HD patients. CACS was assessed by multidetector-row computed tomography and stratified as tertiles: group 1 (0∼105 U), group 2 (110∼1067 U), and group 3 (1094∼15481 U). The duration of follow-up was 7 years and 4 months. Kaplan-Meier method and Cox proportional hazard analysis adjusted for age and HD duration were performed to examine the impact of CACS on survival. MAIN OUTCOME MEASURE: All-cause and cardiovascular mortalities were measured. RESULTS: The cumulative all-cause and cardiovascular mortalities of group 1 were significantly lower than those of groups 2 and 3 (all-cause mortality: 7.6% vs. 43.3% and 52.2%, respectively, cardiovascular mortality: 3.0% vs. 22.4% and 26.9%, respectively). Cox proportional hazard analysis adjusted for age and HD duration revealed that all-cause and cardiovascular mortalities of group 1 were significantly lower than those of groups 2 and 3. CONCLUSION: CACS is helpful to predict prognosis of HD patients independently of age and HD duration.

Sirtuin 1 gene polymorphisms are associated with body fat and blood pressure in Japanese.

Sirtuin 1 (SIRT1) is a longevity gene that protects cells against oxidative and genotoxic stress. This study aimed to investigate the associations of SIRT1 gene single nucleotide polymorphisms (SNPs), rs7895833, rs7069102, and rs2273773, with various laboratory data in 1279 Japanese health checkup examinees. The genotyping was performed using a polymerase chain reaction (PCR) with confronting 2-pair primers (CTPP) assay. Concerning rs7895833 (A allele frequency: 0.290), body fat ratio and body mass index were high in the AA carriers of male subjects, and diastolic blood pressure was high in the AA carriers of female subjects. Concerning rs7069102 (G allele frequency: 0.181), body fat ratio and systolic blood pressure were high in the GG carriers of male subjects. Concerning rs2273773 (C allele frequency: 0.323), fasting glucose and body fat ratio were high in the TT carriers of male subjects, and systolic and diastolic blood pressures were high in the CC carriers of male subjects. Thus, the A allele of rs7895833, G allele of rs7069102, and T allele of rs2273773 carried a high risk for obesity in men. Furthermore, the A allele of rs7895833 in women, and the G allele of rs7069102 and C allele of rs2273773 in men, carried a high risk for hypertension. The T allele of rs2273773 in men carried a high risk for hyperglycemia. In conclusion, these SIRT1 gene polymorphisms are associated with high body fat and blood pressure in Japanese, especially in men. The allele frequencies of rs7895833 and rs7069102, which are different from Caucasians, might explain why Japanese show less marked obesity compared with Caucasians.

KLOTHO gene polymorphisms G-395A and C1818T are associated with low-density lipoprotein cholesterol and uric acid in Japanese hemodialysis patients.

BACKGROUND/AIMS: This study aimed to investigate the association of the KLOTHO gene single nucleotide polymorphisms (SNPs), G-395A and C1818T, with various laboratory data in 219 Japanese hemodialysis (HD) patients. METHODS: The genotyping of G-395A in the promoter region and C1818T in exon 4 was performed using polymerase chain reaction with confronting two-pair primers (PCR-CTPP) assay. RESULTS: In HD patients, the allele frequencies of G-395A were 0.847 for the G allele and 0.153 for the A allele and those of the C1818T were 0.829 for the C allele and 0.171 for the T allele. There were no significant differences in allele frequencies of G-395A and those of the C1818T between HD patients and healthy subjects. Multivariate analysis adjusted for age and duration on HD demonstrated that uric acid was significantly high in A allele carriers of G-395A compared with GG genotype in all and female patients. Low-density lipoprotein cholesterol was significantly low in T allele carriers of C1818T compared with CC genotype in all and male patients. CONCLUSION: KLOTHO gene SNPs G-395A and C1818T are associated with low-density lipoprotein cholesterol and uric acid in HD patients.

KLOTHO gene polymorphisms G-395A and C1818T are associated with lipid and glucose metabolism, bone mineral density and systolic blood pressure in Japanese healthy subjects.

BACKGROUND: We investigated the association of KLOTHO gene single nucleotide polymorphisms (SNPs) with various laboratory data in 476 Japanese healthy subjects. METHODS: The genotyping of G-395A in the promoter region and C1818T in exon 4 was performed using PCR with confronting 2-pair primers assay. RESULTS: Multivariate analysis adjusted for age demonstrated that in men, body-fat ratio was high, and HDL cholesterol level was low in A allele carriers of G-395A compared with GG. In women, glucose was high in A allele carriers of G-395A compared with GG, and also in T allele carriers of C1818T compared with CC. When divided into 2 groups according to age, in men <60 y, body mass index, body-fat ratio and waist circumference were high in A carriers of G-395A compared with GG. In women <60 y, bone mineral density was high in A allele carriers of G-395A compared with GG, and systolic blood pressure and glucose were high in T carriers of C1818T compared with CC. CONCLUSIONS: KLOTHO gene SNPs G-395A and C1818T are associated with lipid metabolism in men, and glucose metabolism, bone mineral density and systolic blood pressure in women.