Two polymorphisms of RCAN1 gene associated with Alzheimer's disease in the Chinese Han population.

OBJECTIVE: Regulator of calcineurin 1 (RCAN1) gene is a regulator on the activity of calcineurin and was reported to be overexpressed in Alzheimer's disease. The aim of this study was to evaluate several polymorphisms of RCAN1, located in the probable promoter region of RCAN1-4 and around the exonic splicing enhancer motifs of RCAN1, in a cohort of Chinese late-onset Alzheimer's disease. METHODS: A pilot case-control study was conducted in 142 Alzheimer's disease patients and 99 nondemented controls from Chinese Han population. Fragments of the RCAN1 including 5 polymorphisms (rs71324311, rs3831376, rs10550296, rs8135540, rs78899361) were amplified and sequenced. RESULTS: In our sample, 2 polymorphisms (rs71324311 and rs10550296) were associated with Alzheimer's disease. Of these 2 polymorphisms, the heterozygous deletion genotype of rs71324311 was more prevalent in non-demented controls than in those with Alzheimer's disease (4% vs. 0%), indicating a slight protective role (Fisher's exact test, p = 0.03; crude odds ratio = 0.96, 95% confidence interval = 0.92-0.99). There was only a trend towards a significant difference in the distributions of genotypes of rs10550296 between 2 groups (chi2 = 1.93; p = 0.17; crude odds ratio = 1.44, 95% confidence interval = 0.85-2.41). However, logistic regression analysis showed that the age-, gender- and apolipoprotein E epsilon4-adjusted odds ratio of Alzheimer's disease with rs10550296 heterozygous deletion genotype was 2.11 (chi2 = 4.42; p = 0.04; 95% confidence interval = 1.05-4.20). CONCLUSIONS: Regarding Alzheimer's disease susceptibility in Chinese Han population, our data suggested a protective role for the rs71324311 heterozygous deletion genotype and a risk role from the rs10550296 heterozygous deletion genotype.

Proteomic analysis of proteins in PC12 cells before and after treatment with nerve growth factor: increased levels of a 43-kDa chromogranin B-derived fragment during neuronal differentiation.

Proteomic analysis is an important approach to characterizing the proteome and studying protein function in the post-genomic era. It is also a powerful screening method for detecting unexpected alterations in protein expression that may be missed by conventional biochemical techniques. The aim of this study was to perform a preliminary proteomic analysis of PC12 cells in order to investigate the effect of nerve growth factor (NGF) on protein expression in PC12 cells during neurite outgrowth. PC12 cell proteins were separated by two-dimensional electrophoresis (2DE) and visualized by silver staining, then certain proteins were identified by N-terminal amino acid microsequencing and a homology search of a protein sequence database. Over 400 proteins were detected, 10% of which showed a significant (greater than 30%) increase or decrease in expression during NGF-induced neuronal differentiation. Seven proteins in the 2DE map were identified; the levels of five of these were unaffected by NGF treatment, whereas the levels of the other two, beta-tubulin and a novel 43-kDa chromogranin B-derived fragment, were significantly increased by more than 30 and 200%, respectively. Our results suggest that chromogranin B processing is enhanced in PC12 cells during NGF-induced neuronal differentiation. In addition, since this increase in the levels of the chromogranin B-derived fragment was specifically blocked by PD98059, we suggest that the increased processing can be ascribed to activation of the MAP kinase pathway, and that the 43-kDa chromogranin B-derived fragment can serve as a new marker of neuronal differentiation for proteomic studies.

Nutritional assessment of rural villages and estates in peninsular Malaysia: Total blood cholesterol values in children, adolescents and adults.

The present study is unique in the Malaysian context on two counts; first, it employs for the first time a functional group approach (groups based on occupational or economic activity) in the assessment of community nutritional status. Second, the study provides on a nationwide-sampling basis, information on total blood cholesterol (TC) levels in rural children (7.0-12.9 years; n = 1921) and adolescents (13.0-17.9 years; n = 753) which were hitherto unavailable. Total blood cholesterol measurements were performed on 7184 subjects ranging from 7 to 75-years-old (males = 3151; females = 4033) from households in 69 rural villages and seven estates in peninsular Malaysia, which were based on selected multistage random sampling according to the household's involvement in the following economic activities: rice farming, rubber smallholding, coconut smallholding, fishing and employment in estates. In all functional groups, TC values increased with age and there was a distinct gender effect, namely females had higher TC values than males throughout the age spectrum analyzed. Mean TC levels for children and adolescents were in the range 3.85-4.37 mmol/L, rising markedly during adulthood to an overall mean of 4.91 ± 1.13 mmol/L for men and 5.17 ± 1.11 mmol/L for women. In adults (>= 18.0 years), there was marked disparity in mean TC values among the functional groups; males and females from rice households had the lowest mean TC values (4.58 and 4.99 mmol/L, respectively). Individuals at 'high risk' (TC > 6.20 mmol/L) averaged 16.0% in women and 11.6% in men, with women from the fishing, rubber and coconut households particularly affected (17.1-21.1%). When compared to earlier rural TC data reported for closely similar rural communities in the peninsula, the present findings suggest a 'hypercholesterolemic shift' approximating 0.39 mmol/L (15 mg/dL) in the adult population; however, this was not apparent in the children and adolescents from these rural communities.

Socio-economic determinants of nutritional status of children in rural peninsular Malaysia.

The data presented is part of the findings from a four-year collaborative research project between Universiti Putra Malaysia, the Institute for Medical Research and the Ministry of Health Malaysia. The project assessed the nutritional status of the major functional groups in Peninsular Malaysia. Mukim Sayong and Pulau Kemiri in the District of Kuala Kangsar, Perak were two of the subdistricts selected to represent small rubber holdings in Peninsular Malaysia. This paper attempts to analyse the socio-economic profile of the households and the nutritional status of children below 9 years of age. A total of 307 households were studied. Approximately 63% of the households were involved in rubber activities and the majority of them were hired tappers. The average monthly income of the households was RM467 and the income ranged between RM30 to RM2120. Based on the per capita poverty line income of RM84.38, it was found that 14.1% of the households earned less than RM42.19, which can be considered as hard-core poor, while 32.7% were poor (monthly per capita income between RM42.19 and RM84.38). Slightly more than half (52.7%) earned income above the poverty line. The average family size was 4.5, ranging from 1 through to 16. The majority of the heads of households (56.6%) had between 3 and 6 years of education, and 14.5% did not receive any formal education. The prevalence of stunting among children 0-5 years of age was 26%, while 31.5% were underweight and 3.8% wasted. Among children aged between 5 and 9 years, almost the same pattern of nutritional status was noted. The overall percentages of stunting, underweight and wasting among these children were 29.2%, 26.1% and 0.62%, respectively. Analysis on nutritional status according to income level showed a noticeable difference in the prevalence of malnutrition in children above and below the poverty line income. The Student's t-test indicated significant differences in weight-for-age and weight-for-height between the two poverty line income for children below 5 years of age. Pearson's correlation coefficient showed a significant correlation between height-for-age with household size (r = -0.26, p<0.05), and monthly per capita income with weight-for-height (r = 0.25, p<0.05). There was a highly significant correlation between acreage of land cultivated and weight-for-height (r = 0.42, p<0.01), and weight-for-age (r = 0.25, p<0.05). The findings indicated the influence of socio-economic factors on the nutritional status of children.

The nutritional situation in metropolitan Kuala Lumpur, with focus on squatters.

Kuala Lumpur is the capital city of Malaysia with an estimated population of 1.55 million. Approximately 12% of the population live in squatter settlements occupying about 7% of the city total area. The squatter settlements generally are provided with basic amenities such as piped water, toilet facilities and electricity. Health indicators for the overall population of Kuala Lumpur are better off than for the rest of the country; however, intra-city differentials prevail along ethnic and socio-economic lines. Malays and Indians have higher rates for stillbirths, and neonatal, infant and toddler mortality than the Chinese. The wide disparity in the socio-economic status between the advantaged and the poor groups in the city is reflected in the dietary practices and nutritional status of young children from these communities. The percentage of preschool children from urban poor households with inadequate intakes of calories and nutrients is two to three times higher than those from the advantaged group. Compared to rural infants, a lower percentage of urban infants are breastfed. A lower percentage of Malays from the urban advantaged group breastfed, compared with the urban poor group. The reversed trend is found for the Chinese community. Growth attainment of young children from the urban poor is worse than the urban advantaged, though better than the rural poor. Health and nutritional practices implications related to both undernutrition and overnutrition are discussed, to illustrate the twin challenges of malnutrition in the city.