Genetic variations of HSD11B2 in hypertensive patients and in the general population, six rare missense/frameshift mutations.

Mutations in the gene encoding 11beta-hydroxysteroid dehydrogenase type 2, HSD11B2, cause a rare monogenic juvenile hypertensive syndrome called apparent mineralocorticoid excess (AME). In AME, defective HSD11B2 enzyme activity results in overstimulation of the mineralocorticoid receptor (MR) by cortisol, causing sodium retention, hypokalemia, and salt-dependent hypertension. Here, we have studied whether genetic variations in HDS11B2 are implicated in essential hypertension in Japanese hypertensives and the general population. By sequencing the entire coding region and the promoter region of HDS11B2 in 953 Japanese hypertensives, we identified five missense mutations in 11 patients (L14F, n = 5; R74H, n = 1; R147H, n = 3; T156I, n = 1; R335H, n = 1) and one novel frameshift mutation (4884Gdel, n = 1) in a heterozygous state, in addition to 19 genetic variations. All genetic variations identified were rare, with minor allele frequencies less than 0.005. Four of 12 patients with the missense/frameshift mutations showed renal failure. Four missense mutations, L14F, R74H, R147H, and R335H, were successfully genotyped in the general population, with a sample size of 3,655 individuals (2,175 normotensives and 1,480 hypertensives). Mutations L14F, R74H, R147H, and R335H were identified in hypertensives (n = 6, 8, 3, and 0, respectively) and normotensives (n = 8, 12, 5, and 0, respectively) with a similar frequency, suggesting that these missense mutations may not strongly affect the etiology of essential hypertension. Since the allele frequency of all of the genetic variations identified in this study was rare, an association study was not conducted. Taken together, our results indicate that missense mutations in HSD11B2 do not substantially contribute to essential hypertension in Japanese.     

Obstinate cough as a sole presenting symptom of non-metastatic renal cell carcinoma

Renal cell carcinoma (RCC) causes many kinds of symptoms such as hypercalcemia, hypertension, polycythemia and fever. Here we describe a rare case of RCC presenting with a persistent cough. After radical nephrectomy, the obstinate cough disappeared. When the tumor recurred locally, the cough also recurred. Furthermore, the cough disappeared completely again after the removal of the recurrent tumor. Although all the clinical findings suggested that the RCC caused the cough, we could not identify a specific humoral substance responsible for the cough.     

Association of sixty-one non-synonymous polymorphisms in forty-one hypertension candidate genes with blood pressure variation and hypertension.

We previously selected a group of hypertension candidate genes by a key word search using the OMIM database of NCBI and validated 525 coding single nucleotide polymorphisms (SNPs) in 179 hypertension candidate genes by DNA sequencing in a Japanese population. In the present study, we examined the association between 61 non-synonymous SNPs and blood pressure variations and hypertension. We used DNA samples taken from 1,880 subjects in the Suita study, a population-based study using randomly selected subjects. Analyses of covariance adjusting for age, body mass index, hyperlipidemia, diabetes, smoking, drinking, and antihypertensive medication revealed that 17 polymorphisms in 16 genes (APOB, CAST, CLCNKB, CTNS, GHR, GYS1, HF1, IKBKAP, KCNJ11, LIPC, LPL, P2RY2, PON2, SLC4A1, TRH, VWF) were significantly associated with blood pressure variations. Multivariate logistic regression analysis with adjustment for the same factors revealed that 11 polymorphisms in 11 genes (CAST, CTLA4, F5, GC, GHR, LIPC, PLA2G7, SLC4A1, SLCI8A1, TRH, VWF) showed significant associations with hypertension. Five polymorphisms in five genes, CAST(calpastatin), LIPC (hepatic lipase), SLC4A1 (band 3 anion transporter), TRH (thyrotropin-releasing hormone), and VWF (von Willebrand factor), were significantly associated with both blood pressure variation and hypertension. Thus, our study suggests that these five genes were susceptibility genes for essential hypertension in this Japanese population.     

A promoter variant of the ATP-binding cassette transporter A1 gene alters the HDL cholesterol level in the general Japanese population

To investigate the effects of polymorphisms in the ATP-binding cassette transporter A1 (ABCA1) gene on the high-density lipoprotein cholesterol (HDL-C) level and the incidence of myocardial infarction (MI), we performed association studies. Sequence analysis identified 14 polymorphisms in the promoter region of ABCA1. After considering linkage disequilibrium, three polymorphisms in the promoter region and 11 polymorphisms from the JSNP database were determined in 1,880 subjects recruited from the Suita Study, representing the general population in Japan. We evaluated the association between the ABCA1 genotype and HDL-C level adjusted not only for standard factors, but also for genetic factors including ApoA1 and ApoE genotypes. Of the 14 polymorphisms tested, the G(–273)C (P=0.0074), C(–297)T (P=0.0195), and IMS-JST071749 (P=0.0093) polymorphisms were significantly associated with the HDL-C level in the Suita population. We could reconfirm that the G(–273)C genotype was influential in another set of subjects (P=0.0310, n=743). However, the distribution of the ABCA1 G(–273)C genotype in subjects with MI (n=598) was not different from that in the control population (n=801). These results indicate that ABCA1 G(–273)C has a significant effect on the HDL-C level in the general Japanese population, but not on the incidence of MI.     

Cross-regional survey of seasonal affective disorders in adults and high-school students in Japan

BACKGROUND: In Asian countries, there is no epidemiological report on seasonal affective disorder (SAD) in different age groups and different geographic regions surveyed at the same time. The aim of this study was to estimate the prevalence rates of SAD and risk factors for SAD in adults and high-school students, with special reference to the difference of winter SAD between northern and southern regions in Japan. METHODS: A total of 3237 high-school students and 4858 workers living in Japan (31.3-43.5 degrees N) responded to this epidemiological survey using Japanese version of the Seasonal Pattern Assessment Questionnaire (SPAQ). RESULTS: The overall prevalence rates of winter SAD (subsyndromal winter SAD) and summer SAD (subsyndromal summer SAD) in high-school students were 0.91(2.21) and 0.81(2.57)%, respectively. In workers, these rates were 0.45(1.16) and 0.43(0.71)%, respectively. Although no regional difference was noted in high-school students with winter seasonal type, the estimated odds ratio of this type for northern workers was nearly 3-fold higher than the southern counterparts. The prevalence rates of each seasonal type were not significantly different between two sexes in both age groups. No clear dependence on latitude was seen with regard to summer SAD in both age groups. LIMITATIONS: The effect of climate on SAD could not be entirely excluded from geophysical factor as indexed by latitude. CONCLUSIONS: SAD was less common in adults than in high-school students. While latitude was a major determinant of winter type in adults, socio-cultural factors or other contributing factors might affect the development of this type in high-school students.     

Personality of seasonal affective disorder analyzed by Tri-dimensional Personality Questionnaire

BACKGROUND: Although there have been numerous reports in personality of mood disorders, there have been few reports in regard with personality of winter seasonal affective disorder (SAD). Furthermore, no reports have been published concerning summer SAD personality characteristics. Thus, this study was conducted to assess the personality of winter and summer SAD using Tri-dimensional Personality Questionnaire (TPQ) that have been used in a variety of mental disorders. METHODS: A total of 6135 Japanese were evaluated with TPQ, the Seasonal Pattern Assessment Questionnaire (SPAQ) and the Self-rating Depression Scale (SDS). Winter, summer and non-SAD groups were classified by SPAQ. We compared the difference of personality trait among these three groups in consideration of gender, age and SDS score influence. RESULTS: Winter SAD demonstrated higher "Novelty Seeking" and "Harm Avoidance"; summer SAD showed higher "Harm Avoidance" than the non-SAD group. "Harm Avoidance" in both SAD groups was re-analyzed using SDS score as a covariate, and "Novelty Seeking" in winter SAD using age as a covariate. As a result, the significance of high "Novelty Seeking" and high "Harm Avoidance" in winter SAD was excluded. However, "Harm Avoidance" remained the significant difference between summer and non-SAD. LIMITATION: SAD was diagnosed only by SPAQ and not by interview. The state-dependency of "Harm Avoidance" was not confirmed in identical patients over lapse of time. CONCLUSION: Patients with winter SAD have high "Harm Avoidance" dependent on the depressive state that is in accordance with non-seasonal depression. Patients with summer SAD have high "Harm Avoidance" possibly independent from the depressive state.     

Measurement of self-propulsion distance of wheelchair using cycle computer excluding assistance distance by touch switch: A pilot study

Objective: Although the propulsion distance of a wheelchair is measured by some devices, measuring self-propulsion distance, excluding assistance propulsion distance by the caregiver, is difficult. This is a pilot study conducted to verify whether the propulsion distance of wheelchair users, excluding the assistance propulsion distance, can be measured using a cycle computer by attaching the touch switch.Methods: The wheelchair propulsion distance was measured using a cycle computer. We connected the touch switch and the cycle computer to the wheelchair to exclude assistance propulsion distance. We set the cycle computer to stop recording while the caregiver was touching the sensor. To confirm the propulsion distance using the cycle computer, the volunteer propelled the wheelchair on a rectangular facility with a total distance of 181 m, and the examiner confirmed the propulsion distance. The validation test to confirm the accuracy of the touch switch attached to the cycle computer was performed on a 50-m straight runway. The volunteer and caregiver propelled the wheelchair alternately by 10 m and continued until 50 m. The examiner confirmed the distance after 50-m propulsion.Results: In the 181-m rectangular facility, the propulsion distance that the volunteer propelled the wheelchair with the cycle computer was 180 m. In the 50-m straight runway, the propulsion distance was 30 m with caregiver assistance for 20 m.Conclusion: The present study showed that our modified device could measure the self-propulsion distance, excluding assistance propulsion distance in wheelchair users.