Environmental factors and risk of aggressive prostate cancer among a population of New Zealand men - a genotypic approach

Prostate cancer is one of the most significant health concerns for men worldwide. Numerous researchers carrying out molecular diagnostics have indicated that genetic interactions with biological and behavioral factors play an important role in the overall risk and prognosis of this disease. Single nucleotide polymorphisms (SNPs) are increasingly becoming strong biomarker candidates to identify susceptibility to prostate cancer. We carried out a gene × environment interaction analysis linked to aggressive and non-aggressive prostate cancer (PCa) with a number of SNPs. By using this method, we identified the susceptible alleles in a New Zealand population, and examined the interaction with environmental factors. We have identified a number of SNPs that have risk associations both with and without environmental interaction. The results indicate that certain SNPs are associated with disease vulnerability based on behavioral factors. The list of genes with SNPs identified as being associated with the risk of PCa in a New Zealand population is provided in the graphical abstrac

Testing the Vitamin D3 metabolic gene variants for association with gout in the New Zealand case-control sample-sets.

Gout is a common disease caused by immune response to monosodium urate (MSU) crystal deposition in articular or periarticular tissues and in the renal tract after chronic hyperuricemia (uric acid levels exceeding 7mg/dL). Gout generally progresses in three clinical stages: asymptomatic hyperuricemia (elevated serum urate levels but no evidence of gout), recurrent episodes of acute gout attacks with interspersed intercritical periods and chronic tophaceous gout (nodular masses of uric acid crystals). Epidemiological evidence have shown the prevalence of gout to be increasing in the New Zealand (NZ) population. In particular Māori (13.9%) and Pacific Island (14.9%) people experience an earlier age of onset and higher frequency of multiple tophi and polyarticular gout. The significant increase of susceptibility to gout in Māori and Pacific Island people in the 21st century has become a public health epidemic. Furthermore inpatients with gout often have a wide variety of co-morbidities including type II diabetes mellitus, congestive heart failure and metabolic syndrome. Vitamin D3 is a secosteroid (steroid molecule with a ‘broken’ ring) hormone and is produced in large quantities in humans upon exposure of skin to sunlight. However most populations are considered to be Vitamin D3 deficient through a combination of environmental, behavioral and genetic factors. Sufficient levels of Vitamin D3 were found to protect against a wide range of diseases including type II diabetes mellitus, cancers and cardiovascular problems. In recent genome wide studies, Vitamin D3 metabolic variants have found to be associated with immune–mediated diseases that are characterized by an imbalance in helper T-cell development. Therefore the aim of this study was to test for associations between Vitamin D3 genetic variants with gout in the NZ case-control sample-sets (Caucasian, Māori, East Polynesian and West Polynesian). Nine single nucleotide polymorphisms (SNPs) from 6 genes were successfully genotyped in the NZ gout cohorts. Case-control analysis was performed for each SNP to test for association of the genomic marker to gout in the NZ gout cohorts. Genotyping data obtained from the NZ gout Caucasian cohort was combined with the Framingham Heart Study (FHS) dataset to provide a more accurate estimate of the overall significance of the SNP to the disease. Although there was some evidence for association with several of the SNPs with gout in the Māori and Eastern Polynesian case-control sample-sets, true association may be distorted by the presence of population stratification within these cohorts. The STRUCTURE and STRAT program was utilized to circumvent the presence of population stratification in this study. However, due to limited number of genomic markers available, population stratification still may not adequately control for the extent of Caucasian ancestry within the Māori and Polynesian case-control sample-sets. The Vitamin D binding protein (VDBP) gene variants, rs7041 and rs4588, showed evidence for association and a trend towards association with gout in the NZ Caucasian case-control sample-set respectively (rs7041: p= 0.02, rs4588: p= 0.05). However both of these variants also conferred strong susceptibility to Vitamin D3 deficiency in the FHS dataset (rs7041: p= 5.4x10-8, rs4588: p= 7.6x10-11). The VDBP gene variants were also tested for association with Rheumatoid arthritis (WTCCC sample-set), presence of tophus (NZ ‘suspected-tophus’ case-control sample-sets) and gender influences with gout presentation (NZ gout case-control sample-sets). These findings suggest that VDBP gene variants may protect an individual against the onset of acute gout. However people with these VDBP gene variants may paradoxically be at a greater risk of developing chronic gout via suppression of Tregulatory cell responses. A further aim of this study was to investigate VDBP gene variants, rs7041 and rs4588 with differences in Vitamin D supplementation and levels of serum 25(OH)D in a separate NZ supplementation sample-set. There was no evidence for differences in binding affinity of the VDBP gene variants with Vitamin D2 (rs7041: p= 0.412, rs4588: p= 0.202) and Vitamin D3 (rs7041: p= 0.408, rs4588: p= 0.432) supplementation and serum 25(OH)D concentrations in the pre-assigned NZ supplement groups. These results suggest that the Vitamin D3 genetic variants may have a profound role in the development of gout. However to obtain any real meaningful etiological effect with gout, Vitamin D3 genetic variants must be genotyped in larger sample-sizes and stratified with increased number of genomic markers to account for Caucasian admixture

Fabrication of Mesoporous Polymers and Their Application as Adsorbents of Aromatic Compounds in Water

主1工学_物質創造工

高分子メソ多孔体の創製ならびに水中の芳香族化合物の吸着材としての応用

主1工学_物質創造工

Noncommunicable disease in rural India: Are we seriously underestimating the risk? The Nallampatti noncommunicable disease study

Aim: To assess the prevalence of noncommunicable diseases in a true rural farming population in South India and compare the data with the landmark contemporary Indian Council of Medical Research-India Diabetes (ICMR-INDIAB) study. Methods: Local Ethics Committee approval and informed consent was obtained from all participants. Inclusion criteria were participants, aged ≥20 and ≤85 years, from Nallampatti, a classical farming village from Tamil Nadu state, India. All participants were administered a detailed questionnaire, had anthropometric measurements including height, weight, and waist circumference. Bloods were drawn for random blood glucose, glycated hemoglobin (HbA1c), nonfasting lipid profile, Cystatin C, uric acid, and hemoglobin. All participants had carotid intima-media thickness (CIMT) done by high-resolution B-mode carotid ultrasound. Results: More than 50% of the population had either diabetes or prediabetes based on HbA1c. Nearly, 40% of the population had hypertension with suboptimal control in those with known hypertension. Nearly, a third of the population had dyslipidemia, elevated cystatin C levels, and abnormal CIMT. The burden was higher than the comparable ICMR-INDIAB study in rural Tamil Nadu. Conclusion: One-third to one-half of this rural farming population is at risk of cardiovascular disease, with poor control of preexisting cardiovascular risk factors. Current Indian data may underestimate the risk in different ethnic populations and regions of India. Long-term follow-up of this cohort for the incident cardiovascular disease will shed light on the true cardiovascular risk in a typical South Indian rural farming population

Differential risk factor profile of diabetes and atherosclerosis in rural, sub‐urban and urban regions of South India: The KMCH‐Non‐communicable disease studies

AimsSouth Asia has emerged rapidly as an epicentre of non- communicable diseases (NCDs) specifically diabetes and cardiovascular diseases. The prevalence rate, risk factors and aetiology of NCDs in different socio- demographic settings are not clearly understood. This study was performed to assess the prevalence of diabetes and atherosclerosis and their risk factors in urban, sub- urban and rural communities of South India.MethodsThree communities [Nallampatti (rural), Thadagam (sub- urban) and Kalapatti (urban)] in South India were selected for participation in the KMCH- NCD Studies. Study volunteers were administered a detailed questionnaire, underwent anthropometric measurements, clinical measurements including blood pressure, glycated haemoglobin (HbA1c), non- fasting lipid profile and serum creatinine. Carotid intima- media thickness was measured using B- mode ultrasound. Multiple logistic regression analyses were performed to understand the association of risk factors with diabetes and atherosclerosis.ResultsA total of 2976 native participants, - ¥20 years of age were screened. The prevalence of diabetes was 16%, 26% and 23% respectively in the rural, sub- urban and urban study populations. Association of obesity with diabetes was observed in only urban population while hypertension and dyslipidaemia showed association in both urban and semi- urban populations. Association of diabetes with atherosclerosis was observed in urban and semi- urban populations. Hypertension in semi- urban and obesity and dyslipidaemia in urban population showed association with atherosclerosis.ConclusionsDiabetes and atherosclerosis burden reported in the three different communities were higher than previous reports, especially in rural and sub- urban regions. No traditional risk factor is identified to be associated with prevalence of diabetes and atherosclerosis in rural population. These findings suggest an urgent need for investigation into the role of non- traditional risk factors like environmental or occupational exposures may help to better understand the aetiology of diseases in non- urbanized communities.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/167761/1/dme14466_am.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/167761/2/dme14466.pd

Differential risk factor profile of diabetes and atherosclerosis in rural, sub- urban and urban regions of South India: The KMCH- Non- communicable disease studies

AimsSouth Asia has emerged rapidly as an epicentre of non- communicable diseases (NCDs) specifically diabetes and cardiovascular diseases. The prevalence rate, risk factors and aetiology of NCDs in different socio- demographic settings are not clearly understood. This study was performed to assess the prevalence of diabetes and atherosclerosis and their risk factors in urban, sub- urban and rural communities of South India.MethodsThree communities [Nallampatti (rural), Thadagam (sub- urban) and Kalapatti (urban)] in South India were selected for participation in the KMCH- NCD Studies. Study volunteers were administered a detailed questionnaire, underwent anthropometric measurements, clinical measurements including blood pressure, glycated haemoglobin (HbA1c), non- fasting lipid profile and serum creatinine. Carotid intima- media thickness was measured using B- mode ultrasound. Multiple logistic regression analyses were performed to understand the association of risk factors with diabetes and atherosclerosis.ResultsA total of 2976 native participants, - ¥20 years of age were screened. The prevalence of diabetes was 16%, 26% and 23% respectively in the rural, sub- urban and urban study populations. Association of obesity with diabetes was observed in only urban population while hypertension and dyslipidaemia showed association in both urban and semi- urban populations. Association of diabetes with atherosclerosis was observed in urban and semi- urban populations. Hypertension in semi- urban and obesity and dyslipidaemia in urban population showed association with atherosclerosis.ConclusionsDiabetes and atherosclerosis burden reported in the three different communities were higher than previous reports, especially in rural and sub- urban regions. No traditional risk factor is identified to be associated with prevalence of diabetes and atherosclerosis in rural population. These findings suggest an urgent need for investigation into the role of non- traditional risk factors like environmental or occupational exposures may help to better understand the aetiology of diseases in non- urbanized communities.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/167761/1/dme14466_am.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/167761/2/dme14466.pd