Association of the RYR3 gene polymorphisms with atherosclerosis in elderly Japanese population

BACKGROUND: The Ryanodine receptor 3 gene (RYR3) encodes an intracellular calcium channel that mediates the efflux of Ca(2+) from intracellular stores. Two single-nucleotide polymorphisms (SNPs) in the RYR3 gene have been shown to associate with stroke (rs877087) and carotid intima-media thickness (rs2229116) in two independent genome-wide association studies (GWAS) in Caucasian. We investigated the effect of these two SNPs as well as the 31.1 kilobases spanning region on atherosclerosis in Japanese population. METHODS: Atherosclerotic severity was assessed by carotid artery (n = 1374) and pathological atherosclerosis index (PAI) (n = 1262), which is a macroscopic examination of the luminal surfaces of 8 systemic arteries in consecutive autopsy samples. 4 tag SNPs in the 31.1 Kb region, rs877087, rs2132207, rs658750 and rs2229116, were genotyped and haplotypes were inferred to study the association with atherosclerotic indices. RESULTS: rs877087 and rs2229116 were associated with PAI (OR = 2.07 [1.04-4.12] (95% CI), p = 0.038; and OR = 1.38 [1.02-1.86], p = 0.035, respectively). rs2229116 was also associated with common carotid atherosclerosis (OR = 1.45 [1.13-1.86], p = 0.003). The risk allele of rs2229116 was opposite from the original report. The haplotype block of this 31.1 Kb region was different between Caucasian and Japanese. Haplotype analysis revealed that only TAGG haplotype was associated with PAI (OR = 0.67 [0.48-0.94], p = 0.020) and atherosclerosis of common carotid artery (OR = 0.75 [0.58-0.98], p = 0.034). CONCLUSION: rs877087 and rs2229116 of RYR3 gene are associated with atherosclerosis severity in Japanese. The functional difference caused by rs2229116 needs to be investigated

A gene variant in the Atp10d gene associates with atherosclerotic indices in Japanese elderly population

AbstractBackgroundATP10D belongs to a subfamily of P-type ATPases implicated in phospholipids translocation from the exoplasmic to the cytoplasmic leaflet of cellular biological membrane. Previous genome-wide association study (GWAS) identified that a variant in Atp10d gene (rs2351791) associates with serum lipid profile and myocardial infarction. The objective of this study is to assess the effect of this variant on atherosclerosis in Japanese elderly population.MethodConsecutive autopsy cases registered in JG-SNP study were recruited (n = 1536). The samples were pathologically assessed for atherosclerosis using macroscopic examination of the formalin-fixed arteries, and coronary stenotic index (CSI), intracranial atherosclerotic index (ICAI) and pathological atherosclerotic index (PAI), which represent systemic arteries were calculated. The variant rs2351791 (G/T) in Atp10d gene was genotyped by Taqman genotyping assay and association determined.ResultBoth CSI and ICAI were significantly higher in GG genotype than GT genotype and TT genotype (p = 0.003 and p = 0.001, respectively). Both associations remained significant in minor allele dominant model after adjusting for age, hypertension, diabetes, HDL, smoking and drinking (p = 0.001 and p = 0.001, respectively). PAI was not associated with this variant. Consistent with the previous report, plasma HDL cholesterol level was lower in GG genotype compared to GT + TT genotypes (p = 0.001).ConclusionThe rs2351791 SNP in the Atp10d gene affects the susceptibility for cardiac and intracranial vascular stenosis in the elderly Japanese population

Semen quality of 1559 young men from four cities in Japan: a cross-sectional population-based study

Objectives: To provide information of semen quality among normal young Japanese men and indicate the frequency of reduced semen quality. Design: Cross-sectional, coordinated studies of Japanese young men included from university areas. The men had to be 18-24 years, and both the man and his mother had to be born in Japan. Background information was obtained from questionnaires. Standardised and quality-controlled semen analyses were performed, reproductive hormones analysed centrally and results adjusted for confounding factors. Setting: Four study centres in Japan (Kawasaki, Osaka, Kanazawa and Nagasaki). Participants: 1559 men, median age 21.1 years, included during 1999-2003. Outcome measures: Semen volume, sperm concentration, total sperm count, sperm motility, sperm morphology and reproductive hormone levels. Results: Median sperm concentration was 59 (95% CI 52 to 68) million/ml, and 9% and 31.9% had less than 15 and 40 million/ml, respectively. Median percentage of morphologically normal spermatozoa was 9.6 (8.8 to 10.3)%. Small, but statistically significant, differences were detected for both semen and reproductive hormone variables between men from the four cities. Overall, the semen values were lower than those of a reference population of 792 fertile Japanese men. Conclusions: Assuming that the investigated men were representative for young Japanese men, a significant proportion of the population had suboptimal semen quality with reduced fertility potential, and as a group they had lower semen quality than fertile men. However, the definitive role-if any-of low semen quality for subfertility and low fertility rates remain to be investigated

Associations between the orexin (hypocretin) receptor 2 gene polymorphism Val308Ile and nicotine dependence in genome-wide and subsequent association studies

Impact of the HCRTR2 gene risk variant on schizotypal personality traits (mean ± SD). (DOC 54 kb

Low Lipoprotein(a) Concentration Is Associated with Cancer and All-Cause Deaths: A Population-Based Cohort Study (The JMS Cohort Study)

Background: Experimental studies support the anti-neoplastic effect of apo(a), but several clinical studies have reported contradictory results. The purpose of this study was to determine whether a low lipoprotein(a) [Lp(a)] concentration is related to mortality from major causes of death, especially cancer. Methods The subjects were 10,413 participants (4,005 men and 6,408 women) from a multi-center population-based cohort study in Japan (The Jichi Medical School cohort study). The average age at registration was 55.0 years, and the median observation period was 4,559 days. As the estimated hazard ratio was high for both the low and very high Lp(a) levels, we defined two Lp(a) groups: a low Lp(a) group [Lp(a)<80 mg/L] and an intermediate-to-high Lp(a) group [Lp(a)≥80]. Participants who died from malignant neoplasms (n = 316), cardiovascular disease (202), or other causes (312) during the observation period were examined. Results: Cumulative incidence plots showed higher cumulative death rates for the low Lp(a) group than for the intermediate-to-high Lp(a) group for all-cause, cancer, and miscellaneous-cause deaths (p<0.001, p = 0.03, and p = 0.03, respectively). Cox proportional hazards analyses with the sex and age of the participants, body mass index, and smoking and drinking histories as covariates showed that a low Lp(a) level was a significant risk for all-cause, cancer, and miscellaneous-cause deaths (p<0.001, p = 0.003, and p = 0.01, respectively). The hazard ratio (95% CI) [1.48, 1.15–1.92] of a low Lp(a) level for cancer deaths was almost the same as that for a male sex (1.46, 1.00–2.13). Conclusions: This is the first report to describe the association between a low Lp(a) level and all-cause or cancer death, supporting the anti-neoplastic effect of Lp(a). Further epidemiological studies are needed to confirm the present results

Accuracy of Death Certificates and Assessment of Factors for Misclassification of Underlying Cause of Death

Background: Cause of death (COD) information taken from death certificates is often inaccurate and incomplete. However, the accuracy of Underlying CODs (UCODs) recorded on death certificates has not been comprehensively described when multiple diseases are present. Methods: A total of 450 consecutive autopsies performed at a geriatric hospital in Japan between February 2000 and August 2002 were studied. We evaluated the concordance rate, sensitivity, and specificity of major UCODs (cancer, heart disease, and pneumonia) reported on death certificates compared with a reference standard of pathologist assessment based on autopsy data and clinical records. Logistic regression analysis was performed to assess the effect of sex, age, comorbidity, and UCODs on misclassification. Results: The concordance rate was relatively high for cancer (81%) but low for heart disease (55%) and pneumonia (9%). The overall concordance rate was 48%. Sex and comorbidity did not affect UCOD misclassification rates, which tended to increase with patient age, although the association with age was also not significant. The strongest factor for misclassification was UCODs (P < 0.0001). Sensitivity and specificity for cancer were very high (80% and 96%, respectively), but sensitivity for heart disease and pneumonia was 60% and 46%, respectively. Specificity for each UCOD was more than 85%. Conclusions: Researchers should be aware of the accuracy of COD data from death certificates used as research resources, especially for cases of elderly patients with pneumonia

Gross Cystic Disease Fluid Protein-15 (GCDFP-15) Expression Characterizes Breast Mucinous Carcinomas in Older Women

The predominant histological subtype of breast mucinous carcinoma in older women is type B (hypercellular type), and, in younger women, it is type A (hypocellular type). The characteristics of mucinous carcinomas of the same histological subtype may differ between older and younger women. This study aims to systematically clarify the pathological/immunohistochemical features of mucinous carcinomas. A total of 21 surgical cases of mucinous carcinoma (type A/B: 9/12 cases) in the older group (&ge;65 years) and 16 cases (type A/B: 14/2 cases) in the younger group (&le;55 years) (n = 37) were included. Gross cystic disease fluid protein-15 (GCDFP-15) and eight other markers were used for immunostaining. The GCDFP-15-positive rate in the older group was high regardless of the histological subtype (type A, 77.8%; type B, 91.7%). The GCDFP-15 positivity in the older group was significantly higher than that in the younger group (p &lt; 0.001 for Allred score). Among type A, GCDFP-15 positivity was significantly higher in the older group than in the younger group (p = 0.042 for the Allred score and p = 0.007 for the positivity rate). The present results suggest that GCDFP-15 expression characterizes mucinous carcinomas in older women

Oestrogen receptor-β CA repeat polymorphism is associated with incidence of colorectal cancer among females

Aims: Increasing evidence suggests an association between oestrogens and colorectal cancer. Oestrogen receptor beta, ER-β, putatively plays a pathobiological role in colorectal cancer as colorectal epithelial cells frequently express ER-β. The aim was to elucidate the association of the dinucleotide (CA) repeat polymorphism of the ER-β gene (ESR2) with colorectal cancer. Methods and results: Deoxyribonucleic acids extracted from the renal cortex of 1488 Japanese autopsies with complete clinical/pathological data were studied. CA repeat polymorphism was determined by polymerase chain reaction using fluorescein-labelled primers. Patients were divided into three genotype groups according to the number of CA repeats of each allele (S\u3c22, L≥22); SS (with two S alleles), SL (with one each S and L allele) and LL (with two L alleles). The presence/absence of colorectal cancers was determined by examining the clinical records and autopsy material. The incidence of colorectal cancer was significantly different according to the ESR2 CA repeat genotype only among females (SS, 37/202=18.3%; SL, 19/332= 5.7%; LL, 5/155=3.2%, P\u3c0.0001). Immunohistochemically, cancers in females with the SS genotype, but not the SL genotype, frequently expressed the C-terminus portion of ER-β1 (wild-type ER-β). Conclusions: A role for ESR2 CA repeat polymorphism in the pathogenesis of colorectal cancer among females is suggested. © 2011 Blackwell Publishing Limited