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1.
J Hum Hypertens ; 30(4): 252-9, 2016 Apr.
Article in English | MEDLINE | ID: mdl-26108363

ABSTRACT

Hypertension is mainly asymptomatic and remains undiagnosed until the disease progresses. The objective of the study was to determine the prevalence of and risk factors for hypertension in rural Bangladesh. Using a population-based cluster random sampling strategy, 3096 adults aged ⩾30 years were recruited from a rural district in Bangladesh. Data collected included two blood pressure (BP) measurements, fasting blood glucose, socio-demographic and anthropometric measurements. Hypertension was defined as systolic BP (SBP) ⩾140 mm Hg or diastolic BP (DBP) ⩾90 mm Hg or self-reported diagnosed hypertension. Logistic regression techniques were used for data analyses. The crude prevalence of hypertension was 40% (95% confidence interval (CI) 38-42%) of which 82% were previously undiagnosed. People from lower socio-economic status (SES) had a significantly higher percentage of undiagnosed hypertension compared with people with higher SES (P<0.001). There was no significant gender difference in severity of hypertension. Males with higher education level compared with no education had a higher prevalence of hypertension (odds ratio 2.34, 95% CI 1.49-3.69). Older age and waist circumference in both genders, and diabetes, lack of physical activity in females were found to be associated with higher prevalence of hypertension. Our research suggests the prevalence of undiagnosed hypertension was higher in the rural area in Bangladesh than that reported from the rural area in neighbouring India and China. Lower SES was associated with a higher risk of undiagnosed hypertension. Public health programs at the grass-roots level must emphasise the provision of primary care and preventive services in managing this non-communicable disease.


Subject(s)
Blood Pressure , Diabetes Mellitus/epidemiology , Hypertension/epidemiology , Rural Health , Adult , Age Factors , Aged , Aged, 80 and over , Bangladesh/epidemiology , Diabetes Mellitus/diagnosis , Female , Humans , Hypertension/diagnosis , Hypertension/physiopathology , Logistic Models , Male , Middle Aged , Multivariate Analysis , Obesity/diagnosis , Obesity/epidemiology , Odds Ratio , Prevalence , Risk Factors , Sedentary Behavior , Severity of Illness Index , Socioeconomic Factors , Waist Circumference
2.
Eye (Lond) ; 29(7): 888-94, 2015 Jul.
Article in English | MEDLINE | ID: mdl-25931170

ABSTRACT

PURPOSE: Smartphone-based Snellen visual acuity charts has become popularized; however, their accuracy has not been established. This study aimed to evaluate the equivalence of a smartphone-based visual acuity chart with a standard 6-m Snellen visual acuity (6SVA) chart. METHODS: First, a review of available Snellen chart applications on iPhone was performed to determine the most accurate application based on optotype size. Subsequently, a prospective comparative study was performed by measuring conventional 6SVA and then iPhone visual acuity using the 'Snellen' application on an Apple iPhone 4. RESULTS: Eleven applications were identified, with accuracy of optotype size ranging from 4.4-39.9%. Eighty-eight patients from general medical and surgical wards in a tertiary hospital took part in the second part of the study. The mean difference in logMAR visual acuity between the two charts was 0.02 logMAR (95% limit of agreement -0.332, 0.372 logMAR). The largest mean difference in logMAR acuity was noted in the subgroup of patients with 6SVA worse than 6/18 (n=5), who had a mean difference of two Snellen visual acuity lines between the charts (0.276 logMAR). CONCLUSION: We did not identify a Snellen visual acuity app at the time of study, which could predict a patients standard Snellen visual acuity within one line. There was considerable variability in the optotype accuracy of apps. Further validation is required for assessment of acuity in patients with severe vision impairment.


Subject(s)
Smartphone/standards , Vision Tests/standards , Visual Acuity/physiology , Aged , Female , Humans , Male , Middle Aged , Mobile Applications , Prospective Studies , Reproducibility of Results , Vision Tests/instrumentation
3.
Eye (Lond) ; 25(1): 66-72, 2011 Jan.
Article in English | MEDLINE | ID: mdl-20966972

ABSTRACT

PURPOSE: Endogenous endophthalmitis (EE) is a sight-threatening emergency and the aetiology is often multifactorial. Delayed diagnosis may exacerbate the poor visual prognosis. We describe the management and visual outcomes of EE presenting to a tertiary referral centre. PATIENTS AND METHODS: A prospective consecutive case series of 64 patients presenting with presumed EE from 1997 to 2007 to the Royal Victorian Eye and Ear Hospital were included. All data were collected in a standardized manner. Outcome measures included: visual acuity, microbial profiles, and vitrectomy rate. RESULTS: In total, 64 cases of EE were identified over the study period with a mean age of 57.5 years, and 53.5% were male. Presenting acuities ranged from Snellen 6/6 to no perception of light (NPL). Identifiable risk factors were present in 78.1%, with the majority related to intravenous drug abuse. A 64.1% culture positivity rate was recorded. A vitrectomy rate of 57, 56, and 21% was recorded in documented bacterial, fungal, and no growth cases, respectively. Final Snellen acuities ranged from 6/6 to NPL. A total of 5 out of 64 eyes were enucleated, of which 3 identified Klebsiella species. Better visual outcome was documented in fungal cases. CONCLUSION: EE is a serious ocular condition and has a varied aetiology. Visual outcomes are often poor, irrespective of the method of management. Fungal aetiology often confers a better prognosis, and vitrectomy is advocated for bacterial proven cases.


Subject(s)
Endophthalmitis , Adult , Aged , Aged, 80 and over , Australia , Bacteria/isolation & purification , Endophthalmitis/microbiology , Endophthalmitis/physiopathology , Endophthalmitis/therapy , Eye Infections, Bacterial , Female , Fungi/isolation & purification , Humans , Incidence , Male , Middle Aged , Prognosis , Prospective Studies , Risk Factors , Visual Acuity , Vitrectomy/statistics & numerical data , Young Adult
4.
Bull Environ Contam Toxicol ; 85(3): 301-6, 2010 Sep.
Article in English | MEDLINE | ID: mdl-20658225

ABSTRACT

Arsenic concentrations were measured in water, soil and arum (vegetables) samples using the Neutron Activation Analysis method and a correlation between arsenic concentrations in the samples was investigated. The case study at Bagerhat, Bangladesh revealed that almost all the water samples were contaminated by a hazardous level of arsenic that exceeding the World Health Organization recommended value of 0.05 mg/L for Bangladesh. Arsenic concentration of all the water samples ranged from 0.09 to 0.87 mg/L. The concentrations in soil and aurum samples were found to be in the range of 2.22-35.21 and 0.07-0.73 mg/kg, respectively. A positive correlation between arsenic concentrations in soil and water samples was observed. Aurum sample was found to be contaminated by arsenic to a harmful level if the corresponding water sample was also highly contaminated.


Subject(s)
Arsenic/analysis , Environmental Monitoring/methods , Environmental Pollutants/analysis , Neutron Activation Analysis , Vegetables/chemistry , Arsenic/chemistry , Bangladesh , Environmental Pollutants/chemistry , Fresh Water/chemistry , Soil/analysis
5.
Diabetologia ; 53(9): 2042-5, 2010 Sep.
Article in English | MEDLINE | ID: mdl-20523965

ABSTRACT

AIMS/HYPOTHESIS: The fractal dimension (D(f)) of the retinal vasculature is a global measure of its branching pattern complexity. We examined the relationship of retinal D(f) with diabetes. METHODS: We conducted a cross-sectional study of 1,577 participants with diabetes and impaired glucose metabolism and normal controls from the population-based Australian Diabetes, Obesity and Lifestyle (AusDiab) study. Retinal D(f) was quantified from fundus photographs using a computer-based programme and diabetes status was determined by oral glucose tolerance test based on the WHO criteria. RESULTS: After adjustment for age, sex and vascular risk factors, persons with higher retinal D(f) were more likely to have diabetes (OR 1.56; 95% CI 1.14-2.14, highest vs lowest fractal tertile). This relationship remained with further adjustment for retinal arteriolar calibre and presence of retinopathy (OR 1.64; 95% CI 1.19-2.27), and after excluding participants with retinopathy (OR 1.60; 95% CI 1.16-2.21). Retinal D (f) was not related to impaired glucose tolerance or impaired fasting glucose (OR 1.19; 95% CI 0.85-1.67). CONCLUSIONS/INTERPRETATION: Individuals with diabetes, but not with impaired glucose metabolism, have greater retinal D(f), reflecting greater complexity of the retinal vasculature. Our findings suggest the presence of early microvascular changes in the retinal vasculature of persons with diabetes, even in the absence of overt retinopathy.


Subject(s)
Diabetes Mellitus/pathology , Diabetic Retinopathy/pathology , Glucose Intolerance/pathology , Retinal Vessels/pathology , Cross-Sectional Studies , Diabetic Retinopathy/physiopathology , Female , Glucose Intolerance/physiopathology , Humans , Life Style , Male , Middle Aged , Retinal Vessels/physiopathology
6.
Mol Vis ; 15: 1390-7, 2009 Jul 17.
Article in English | MEDLINE | ID: mdl-19626135

ABSTRACT

PURPOSE: The Retinoic Acid Receptor Alpha (RARA) gene is a potential candidate gene for myopia due to its differential expression in animal models during experimentally induced myopia. To test for whether RARA is associated with myopia we have undertaken a case-control study assessing for associations between RARA and myopia, hypermetropia, and ocular biometric measures. METHODS: A total of 802 Anglo-Celtic individuals were genotyped. Five tag single nucleotide polymorphisms (tSNPs) in RARA with an r(2) of 0.8 and a minor allele frequency greater than 5% were selected for genotyping. Genotype frequencies of these 5 tSNPs were compared between individuals with emmetropia and those with myopia or hypermetropia. A quantitative analysis was also performed to assess associations with ocular biometric measures including axial length, corneal curvature and anterior chamber depth. RESULTS: We did not identify any significant association between tSNPs in RARA with either myopia or hypermetropia as qualitative traits. Neither did we identify any significant associations of these tSNPs with the quantitative traits of axial length, corneal curvature and anterior chamber depth. CONCLUSIONS: This is the first study to assess for associations between RARA and myopia, hypermetropia, and ocular biometric measures. Our findings suggest that variations in the nucleotide sequence of RARA are not associated with myopia, hypermetropia, or ocular biometric measures in our population.


Subject(s)
Biometry , Eye/pathology , Genetic Predisposition to Disease , Hyperopia/genetics , Myopia/genetics , Receptors, Retinoic Acid/genetics , Demography , Female , Humans , Hyperopia/physiopathology , Linkage Disequilibrium/genetics , Male , Middle Aged , Myopia/physiopathology , Polymorphism, Single Nucleotide/genetics , Refraction, Ocular , Retinoic Acid Receptor alpha
7.
Ophthalmic Res ; 41(3): 154-9, 2009.
Article in English | MEDLINE | ID: mdl-19321937

ABSTRACT

OBJECTIVE: It was the aim of this study to assess the role of birth weight in the development of myopia using a large cohort of Caucasian monozygotic (MZ) and dizygotic (DZ) twins that took part in the Genes in Myopia (GEM) twin study. METHODS: The recruitment of all twins in the GEM twin study was facilitated by the Australian Twin Registry. Each twin underwent a standard questionnaire and a comprehensive ocular examination, which included a dilated objective refraction through autorefraction. Myopia was defined as spherical equivalent equal to or worse than -0.50 diopters. Birth weight was determined through self-report as part of the standard questionnaire. RESULTS: A total of 1,224 twins (690 MZ and 534 DZ twins) aged between 18 and 86 years (mean age 52.36 years) were recruited into the GEM study. The mean birth weight was similar between MZ (2.34 kg) and DZ twins (2.46 kg; p > 0.05). Logistic regression showed no significant association with birth weight and myopia for all twins (p = 0.26), as well as for MZ (p = 0.18) and DZ twins (p = 0.70) separately, with no gender effect (p = 0.23). Moreover, there was no significant difference in mean birth weight between discordant (presence/absence) MZ (myopes = 2.33 kg, non-myopes = 2.39 kg) and DZ twin pairs (myopes = 2.39 kg, non-myopes = 2.43 kg; p = 0.91 and 0.95, respectively). CONCLUSION: Birth weight appears to have little to no role in the development of myopia. In addition, birth weight was not a predictor of the discordance of myopia in MZ and DZ twin pairs.


Subject(s)
Birth Weight/genetics , Diseases in Twins/genetics , Myopia/genetics , Twins, Dizygotic , Twins, Monozygotic , Adolescent , Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Registries , Surveys and Questionnaires , White People
8.
Eye (Lond) ; 23(8): 1719-24, 2009 Aug.
Article in English | MEDLINE | ID: mdl-19079148

ABSTRACT

PURPOSE: To describe the relationship of retinal vascular calibre with diabetes and diabetic retinopathy in an Asian population. METHODS: A total of 3280 (78.7% response) subjects, aged 40-80 years, of Malay ethnicity residing in Singapore participated in this population-based, cross-sectional study. Retinal vascular calibre was measured and summarized using a validated computer programme from digital retinal photographs. Diabetic retinopathy signs were graded from photographs using the modified Airlie House classification. RESULTS: Of the 3004 subjects with data for this analysis, 682 (22.7%) had diabetes, of whom 194 (28.4%) had retinopathy. After multivariable adjustment, retinal arteriolar calibre was significantly wider in persons with diabetes (141 vs139 microm, P<0.001); venular calibre was not associated with diabetes (P=0.93). Among participants with diabetes, venular calibre increased from 218.7 microm in those without retinopathy to 231.1 microm in those with moderate and 231.4 microm in those with severe retinopathy (Pfor trend=<0.001); arteriolar calibre was not associated with diabetic retinopathy. CONCLUSIONS: This study shows wider retinal arterioles in diabetes and wider venules in those with diabetic retinopathy in an Asian population. These findings confirm earlier data on white population, supporting the concept that a quantitative assessment of retinal vasculature may provide further insights into early diabetic microvascular damage.


Subject(s)
Diabetic Retinopathy/pathology , Retinal Vessels/pathology , Adult , Aged , Aged, 80 and over , Analysis of Variance , Arterioles/pathology , Asian People , Cross-Sectional Studies , Female , Humans , Indonesia/ethnology , Male , Middle Aged , Multivariate Analysis , Singapore , Venules/pathology
9.
Br J Ophthalmol ; 92(10): 1316-9, 2008 Oct.
Article in English | MEDLINE | ID: mdl-18684751

ABSTRACT

AIM: To describe the prevalence and risk factors of retinal vein occlusion (RVO) in an Asian population. METHODS: The Singapore Malay Eye Study is a population-based, cross-sectional study of 3280 (78.7%) Malay adults (aged 40-80 years) living in Singapore. All participants underwent retinal photography, standardised interview, clinical examinations and laboratory investigations. RVO (central or branch) was graded based on the Blue Mountains Eye Study (BMES) protocol from retinal photographs. RESULTS: The overall prevalence of RVO was 0.7% (n = 22) (95% CI 0.4 to 1.0) (18 branch and five central RVO cases). There was no significant gender difference in RVO prevalence. RVO was associated with higher systolic blood pressure (age-adjusted odds ratio (OR) per SD increase 1.54, CI 1.02 to 2.31), ocular perfusion pressure (OR per SD increase 1.49, CI 1.03 to 2.16), a history of angina (OR 5.18, CI 1.49 to 18.0) and heart attack (OR 4.26, CI 1.47 to 12.3), and higher total cholesterol (OR per SD increase 1.55, CI 1.07 to 2.24) and LDL (OR per SD increase 1.47, CI 1.02 to 2.12) cholesterol levels. CONCLUSIONS: The prevalence of RVO in this Asian population was lower than Caucasians in the BMES, although the systemic associations of RVO were largely similar to BMES and other studies.


Subject(s)
Cardiovascular Diseases/complications , Retinal Vein Occlusion/ethnology , Adult , Aged , Aged, 80 and over , Asian People/ethnology , Cardiovascular Diseases/ethnology , Cross-Sectional Studies , Female , Humans , Hypercholesterolemia/ethnology , Intraocular Pressure , Male , Middle Aged , Prevalence , Retinal Vein Occlusion/diagnosis , Risk Factors , Singapore/ethnology
10.
Osteoporos Int ; 19(7): 961-8, 2008 Jul.
Article in English | MEDLINE | ID: mdl-18038243

ABSTRACT

UNLABELLED: The 1p36 region of the human genome has been identified as containing a QTL for BMD in multiple studies. We analysed the TNFRSF1B gene from this region, which encodes the TNF receptor 2, in two large population-based cohorts. Our results suggest that variation in TNFRSF1B is associated with BMD. INTRODUCTION: The TNFRSF1B gene, encoding the TNF receptor 2, is a strong positional and functional candidate gene for impaired bone structure through the role that TNF has in bone cells. The aims of this study were to evaluate the role of variations in the TNFRSF1B gene on bone structure and osteoporotic fracture risk in postmenopausal women. METHODS: Six SNPs in TNFRSF1B were analysed in a cohort of 1,190 postmenopausal Australian women, three of which were also genotyped in an independent cohort of 811 UK postmenopausal women. Differences in phenotypic means for genotype groups were examined using one-way ANOVA and ANCOVA. RESULTS: Significant associations were seen for IVS1+5580A>G with BMD and QUS parameters in the Australian population (P = 0.008 - 0.034) and with hip BMD parameters in the UK population (P = 0.005 - 0.029). Significant associations were also observed between IVS1+6528G>A and hip BMD parameters in the UK cohort (P = 0.0002 - 0.003). We then combined the data from the two cohorts and observed significant associations between both IVS1+5580A>G and IVS1+6528G>A and hip BMD parameters (P = 0.002 - 0.033). CONCLUSIONS: Genetic variation in TNFRSF1B plays a role in the determination of bone structure in Caucasian postmenopausal women, possibly through effects on osteoblast and osteoclast differentiation.


Subject(s)
Bone Density/genetics , Fractures, Bone/genetics , Osteoporosis, Postmenopausal/genetics , Polymorphism, Single Nucleotide , Receptors, Tumor Necrosis Factor, Type II/genetics , Aged , Aged, 80 and over , Amino Acids/blood , Australia/epidemiology , Cohort Studies , Female , Fractures, Bone/epidemiology , Genotype , Humans , Middle Aged , Osteocalcin/blood , Osteoporosis, Postmenopausal/blood , Osteoporosis, Postmenopausal/urine , Prevalence , United Kingdom/epidemiology
11.
Bone ; 40(1): 175-81, 2007 Jan.
Article in English | MEDLINE | ID: mdl-16949901

ABSTRACT

Bone mass is the single most important risk factor for osteoporotic fractures in the elderly and is mainly influenced by genetic factors accounting for 40-75% of the inter-individual variation. Critical for the bone remodeling process is the balance between the newly discovered members of the tumor necrosis factor ligand and receptor superfamilies, osteoprotegerin (OPG) and receptor activator of nuclear factor-kappaB ligand, which mediate the effects of many upstream regulators of bone metabolism. In the present study, we evaluated the impact of sequence variations in the OPG gene on bone mass, bone-related biochemistry including serum OPG and fracture frequency in elderly Australian women. A total of 1101 women were genotyped for 3 different single nucleotide polymorphisms (SNP) within the OPG gene (G1181C, T950C and A163G). The effects of these SNPs and serum OPG on calcaneal quantitative ultrasound measurements, osteodensitometry of the hip and bone-related biochemistry were examined. We found no significant relationship between sequence variations in the OPG gene or serum OPG and bone mass, bone-related biochemistry or fracture frequency. Our findings confirm some recent publications investigating the same SNPs but diverge from others, indicating that generalization of the relationships found in this type of study must be done with caution and signify the importance of determining associations between polymorphisms and osteoporosis in different ethnic groups.


Subject(s)
Osteoporosis/blood , Osteoporosis/genetics , Osteoprotegerin/blood , Osteoprotegerin/genetics , Polymorphism, Single Nucleotide , Absorptiometry, Photon , Aged , Aged, 80 and over , Australia , Bone Density/genetics , Bone and Bones/diagnostic imaging , Bone and Bones/metabolism , Bone and Bones/ultrastructure , Cohort Studies , Female , Fractures, Spontaneous/blood , Fractures, Spontaneous/genetics , Gene Frequency , Haplotypes , Humans , Linkage Disequilibrium
12.
Diabetologia ; 49(5): 863-71, 2006 May.
Article in English | MEDLINE | ID: mdl-16518589

ABSTRACT

AIMS/HYPOTHESIS: We assessed the effects of type 1 and type 2 diabetes on bone density and metabolism. MATERIALS AND METHODS: We analysed bone mineral density (BMD) measured at the hip, spine and forearm using dual energy X-ray absorptiometry in 34 patients with type 1 and 194 patients with type 2 diabetes. Patients were from the community-based Fremantle Diabetes Study, and findings for them were compared with those from normal age- and sex-matched control subjects from the local community. Biochemical and hormonal markers of bone metabolism were measured in a subset of 70 patients. RESULTS: After adjusting for age and BMI, there was a lower BMD at total hip (p<0.001) and femoral neck (p=0.012) in type 1 men vs control subjects, but type 1 women and matched controls had similar BMD at each site. There was a higher BMD at total hip (p=0.006), femoral neck (p=0.026) and forearm (p<0.001) in type 2 women vs control subjects, but diabetes status was not associated with BMD in type 2 men after adjustment for age and BMI. Serum oestradiol, BMI, C-terminal telopeptide of collagen type 1 and male sex were consistently and independently associated with BMD at forearm, hip and femoral neck and explained 61, 55 and 50% of the total variance in BMD, respectively, at these sites. Spine BMD was independently associated with BMI and ln(oestradiol). CONCLUSIONS/INTERPRETATION: Men with type 1 diabetes may be at increased risk of osteoporosis, while type 2 women appear to be protected even after adjusting for BMI. Low serum oestradiol concentrations may predispose to diabetes-associated osteoporosis regardless of sex.


Subject(s)
Bone Density/physiology , Diabetes Mellitus, Type 1/physiopathology , Diabetes Mellitus, Type 2/physiopathology , Absorptiometry, Photon , Adult , Aged , Blood Chemical Analysis , Blood Glucose/analysis , Blood Pressure , Body Mass Index , Diabetes Mellitus, Type 1/blood , Diabetes Mellitus, Type 2/blood , Fasting , Glycated Hemoglobin/analysis , Humans , Middle Aged , Western Australia
13.
Calcif Tissue Int ; 77(3): 145-51, 2005 Sep.
Article in English | MEDLINE | ID: mdl-16151675

ABSTRACT

Osteoporosis is known to have a strong genetic basis. It has been proposed that polymorphisms within the KL (klotho) gene have a significant effect on aging, in particular, the osteoblast defect of aging. The association between polymorphisms within this gene and biochemical markers of bone formation and resorption, bone structure, and fracture rates was studied in 1,190 postmenopausal women with a mean age of 75 years. Genotyping of these polymorphic sites was carried out using Matrix-Assisted Laser Desorption Ionization--Time of Flight (MALDI-ToF) mass spectrometry. The G allele of SNP c.1775G>A was associated with a lower osteocalcin level than the A allele (P = 0.004) in a codominant model. SNPs C-387T and IVS1+8262c>t both showed nonsignificant associations with osteocalcin (P values of 0.063 and 0.068, respectively), but a haplotype analysis of 2 of 5 haplotypes of the three SNPs with a frequency greater than 4% revealed a significant association with osteocalcin (P = 0.036). None of the individual polymorphisms or haplotypes analyzed showed any associations with a marker of bone resorption the deoxypyridinoline creatinine ratio, bone structure, or fracture data. Therefore, the G polymorphism within the c.1775G>A SNP site and a haplotype including this are associated with a reduced osteoblast product osteocalcin. These data suggest that variation in the KL gene product affects osteoblast activity independent of osteoclast activity but that this defect does not result in an effect on bone structure in this population, perhaps because of "rescue" by other genetic or environmental factors in this population.


Subject(s)
Aging/genetics , Bone Density , Genetic Predisposition to Disease , Membrane Proteins/genetics , Osteocalcin/blood , Osteoporosis, Postmenopausal/genetics , Polymorphism, Single Nucleotide , Absorptiometry, Photon , Aged , Aging/metabolism , Biomarkers/blood , Bone and Bones/diagnostic imaging , Bone and Bones/metabolism , Calcaneus/diagnostic imaging , Female , Fractures, Spontaneous/epidemiology , Fractures, Spontaneous/genetics , Glucuronidase , Haplotypes , Humans , Klotho Proteins , Linkage Disequilibrium/genetics , Membrane Proteins/metabolism , Osteoporosis, Postmenopausal/blood , Osteoporosis, Postmenopausal/diagnosis , Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization/methods , Ultrasonography , Western Australia/epidemiology
14.
Bone ; 36(4): 599-606, 2005 Apr.
Article in English | MEDLINE | ID: mdl-15777745

ABSTRACT

Postmenopausal osteoporosis and bone mass are influenced by multiple factors including genetic variation. The importance of LDL receptor-related protein 5 (LRP5) for the regulation of bone mass has recently been established, where loss of function mutations is followed by severe osteoporosis and gain of function is related to increased bone mass. The aim of this study was to evaluate the role of polymorphisms in the LRP5 gene in regulating bone mass and influencing prospective fracture frequency in a well-described, large cohort of normal, ambulatory Australian women. A total of 1301 women were genotyped for seven different single nucleotide polymorphisms (SNPs) within the LRP5 gene of which five were potentially informative. The effects of these gene polymorphisms on calcaneal quantitative ultrasound measurements (QUS), osteodensitometry of the hip and bone-related biochemistry was examined. One SNP located in exon 15 was found to be associated with fracture rate and bone mineral density. Homozygosity for the less frequent allele of c.3357 A > G was associated with significant reduction in bone mass at most femoral sites. The subjects with the GG genotype, compared to the AA/AG genotypes showed a significant reduction in BUA and total hip, femoral neck and trochanter BMD (1.5% P = 0.032; 2.7% P = 0.047; 3.6% P = 0.008; 3.1% P = 0.050, respectively). In the 5-year follow-up period, 227 subjects experienced a total of 290 radiologically confirmed fractures. The incident fracture rate was significantly increased in subjects homozygous for the GG polymorphism (RR of fracture = 1.61, 95% CI [1.06-2.45], P = 0.027). After adjusting for total hip BMD, the fracture rate was still increased (RR = 1.67 [1.02-2.78], P = 0.045), indicating factors other than bone mass are of importance for bone strength. In conclusion, genetic variation in LRP5 seems to be of importance for regulation of bone mass and osteoporotic fractures.


Subject(s)
Fractures, Bone/genetics , LDL-Receptor Related Proteins/genetics , Organ Size , Polymorphism, Single Nucleotide , Absorptiometry, Photon , Aged , Aged, 80 and over , Australia , Bone Density , Cohort Studies , Female , Haplotypes , Heterozygote , Humans , Linkage Disequilibrium , Low Density Lipoprotein Receptor-Related Protein-5
15.
Bone ; 36(3): 555-61, 2005 Mar.
Article in English | MEDLINE | ID: mdl-15777683

ABSTRACT

The pathogenesis of osteoporosis involves both genetic and environmental factors. On the basis of linkage data suggesting gene effects on bone density at chromosome 14q and data locating the BMP4 gene to 14q, we performed a positional candidate study to examine a possible association of BMP4 gene polymorphisms, hip bone density (n = 1012) and fracture rates (n = 1232) in postmenopausal women (mean age 75). On genotype analysis of the three selected single nucleotide polymorphisms (SNP), the 6007C > T polymorphism was associated with total and intertrochanteric hip BMD and BMD was lower in the 32% of subjects homozygous for the C allele. This polymorphism codes for a nonsynonymous amino acid change with the T allele coding for valine, while the C allele codes for alanine. The difference in BMD was 3.1% (TT vs. CC) and 2.3% (CT versus CC) for the total hip (P = 0.023), and 3.7% (TT vs. CC) and 2.8% (CT versus CC) for the intertrochanter site (P = 0.012). Haplotype analysis demonstrated 6 haplotypes of frequency greater than 2%. A major haplotype defined by G-C-T alleles in SNPs -5826G > A, 3564C > T and 6007C > T respectively, showed association with high bone mass. No SNP showed association with fracture rates. We conclude that a polymorphism found in the BMP4 gene, affecting amino acid sequence, is associated with hip bone density in postmenopausal women, presumably via regulation of anabolic effects on the skeleton.


Subject(s)
Alleles , Bone Density/genetics , Bone Morphogenetic Proteins/genetics , Osteoporosis, Postmenopausal/genetics , Polymorphism, Genetic/genetics , Aged , Aged, 80 and over , Bone Morphogenetic Protein 4 , Female , Humans
16.
Plant Foods Hum Nutr ; 58(4): 285-97, 2003.
Article in English | MEDLINE | ID: mdl-15354788

ABSTRACT

Common beans (Phaseolus vulgaris L) contain a number of antinutritional factors such as condensed tannins. Reducing tannin concentration might contribute to improving the nutritional quality of common bean. But polyphenolics are involved in resistance to diseases and pests, and reducing tannin concentration may have a negative effect on plant resistance. Furthermore, the effects of tannin on disease resistance in different gene pools or in different seed colors are not defined. To investigate these effects, 790 accessions from a common bean core collection were investigated. Data were subjected to independent sample t-tests, and the calculation of correlation coefficients. The mean coat extracts of black and red bean classes were highest (with 0.129 g/g and 0.124 g/g of seed coat, respectively). Among the gene pools, the coat extract was greater in the Middle American gene pool (0.129 g/g) than in the Andean gene pool (0.108 g/g). Coat extract in the Andean gene pool was positively correlated with susceptibility to Middle American isolates of anthracnose and to common bacterial blight, but negatively correlated with susceptibility to Andean isolates of angular leaf spot and to empoasca. Only empoasca damage showed negative correlation with coat extract in the Middle American gene pool. However within gene pools, the coat extracts of different seed classes varied in correlations with reactions to disease and pest infestations. Significant correlations were particularly associated with the black seed class in both gene pools. The relationships between coat extract and disease reactions are complex. A better understanding will help breeders to select germplasm with improved nutritional quality without adversely affecting disease resistance.


Subject(s)
Pest Control, Biological , Phaseolus/physiology , Plant Diseases/genetics , Seeds/physiology , Tannins/immunology , Breeding , Color , Gene Pool , Genotype , Immunity, Innate/physiology , Phaseolus/genetics , Plant Diseases/microbiology , Seeds/genetics
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