Dietary patterns and chronic kidney disease: a cross-sectional association in the Irish Nun Eye Study

Associations between dietary patterns and chronic kidney disease are not well established, especially in European populations. We conducted a cross-sectional study of 1033 older Irish women (age range 56–100 years) with a restricted lifestyle. Dietary intake was assessed using a food frequency questionnaire. Renal function was determined by estimated glomerular filtration rate. Two dietary patterns were identified within the study population using factor analysis. A significant negative association was found between unhealthy dietary pattern adherence and renal function in both unadjusted and adjusted models controlling for potential confounding variables (p for trend <0.001), with a mean difference in estimated glomerular filtration rate of −6 ml/min/1.73 m2 between those in the highest fifth of adherence to the unhealthy dietary pattern compared to the lowest, in the fully adjusted model. Chronic kidney disease risk was significantly greater for the highest fifth, compared to the lowest fifth of unhealthy dietary pattern adherence in adjusted models (adjusted odds ratio = 2.62, p < 0.001). Adherence to the healthy dietary pattern was not associated with renal function or chronic kidney disease in adjusted models. In this cohort, an unhealthy dietary pattern was associated with lower renal function and greater prevalence of chronic kidney disease

Neovascular Age-Related Macular Degeneration Risk Based on CFH, LOC387715/HTRA1, and Smoking

Anne Hughes and colleagues show that an individual's risk of developing age-related macular degeneration in old age can be predicted by combining haplotype data with smoking status

Pathogenic alleles in microtubule, secretory granule and extracellular matrix-related genes in familial keratoconus.

Keratoconus is a common corneal defect with a complex genetic basis. By whole exome sequencing of affected members from 11 multiplex families of European ancestry, we identified 23 rare, heterozygous, potentially pathogenic variants in 8 genes. These include nonsynonymous single amino acid substitutions in HSPG2, EML6 and CENPF in two families each, and in NBEAL2, LRP1B, PIK3CG and MRGPRD in three families each; ITGAX had nonsynonymous single amino acid substitutions in two families and an indel with a base substitution producing a nonsense allele in the third family. Only HSPG2, EML6 and CENPF have been associated with ocular phenotypes previously. With the exception of MRGPRD and ITGAX, we detected the transcript and encoded protein of the remaining genes in the cornea and corneal cell cultures. Cultured stromal cells showed cytoplasmic punctate staining of NBEAL2, staining of the fibrillar cytoskeletal network by EML6, while CENPF localized to the basal body of primary cilia. We inhibited the expression of HSPG2, EML6, NBEAL2 and CENPF in stromal cell cultures and assayed for the expression of COL1A1 as a readout of corneal matrix production. An upregulation in COL1A1 after siRNA inhibition indicated their functional link to stromal cell biology. For ITGAX, encoding a leukocyte integrin, we assayed its level in the sera of 3 affected families compared with 10 unrelated controls to detect an increase in all affecteds. Our study identified genes that regulate the cytoskeleton, protein trafficking and secretion, barrier tissue function and response to injury and inflammation, as being relevant to keratoconus

Retinal microvascular network attenuation in Alzheimer's disease

AbstractIntroductionCerebral small-vessel disease has been implicated in the development of Alzheimer's disease (AD). The retinal microvasculature enables the noninvasive visualization and evaluation of the systemic microcirculation. We evaluated retinal microvascular parameters in a case-control study of AD patients and cognitively normal controls.MethodsRetinal images were computationally analyzed and quantitative retinal parameters (caliber, fractal dimension, tortuosity, and bifurcation) measured. Regression models were used to compute odds ratios (OR) and confidence intervals (CI) for AD with adjustment for confounders.ResultsRetinal images were available in 213 AD participants and 294 cognitively normal controls. Persons with lower venular fractal dimension (OR per standard deviation [SD] increase, 0.77 [CI: 0.62–0.97]) and lower arteriolar tortuosity (OR per SD increase, 0.78 [CI: 0.63–0.97]) were more likely to have AD after appropriate adjustment.DiscussionPatients with AD have a sparser retinal microvascular network and retinal microvascular variation may represent similar pathophysiological events within the cerebral microvasculature of patients with AD

Familial keratoconus with cataract: Linkage to the long arm of chromosome 15 and exclusion of candidate genes

PURPOSE. Keratoconus and cataract are common causes of visual morbidity. Both conditions show genetic predisposition. The purpose of this study was to map the disease locus in a large three-generation family affected by combined early-onset autosomal dominant anterior polar cataract and clinically severe keratoconus. Uniquely, in this family both disorders were present and fully penetrant in those affected. METHODS. Thirty members of the family were examined clinically on two occasions, at an interval of 5 years, to establish their phenotypes and determine the progression of the disease. Genomic DNA was extracted from blood samples of 16 affected and 14 unaffected individuals, and typed with more than 350 highly polymorphic microsatellite loci in a genome-wide linkage screen. Markers were amplified by PCR with fluorescently labeled primers and sized with an automated DNA analyser before calculation of lod scores. After linkage was established, several positional candidate genes were assessed by PCR-based DNA sequencing. RESULTS. The locus for keratoconus with cataract was mapped to a 6.5-Mb region of the long arm of chromosome 15, at 22.33-24.2 between CYP11A and D15S211. The positional and functional candidate genes CTSH, CRABP1, IREB2, and RAS-GRF1 were excluded as the cause of keratoconus with cataract in this family. CONCLUSIONS. This is the first report of a family with autosomal dominant inheritance of keratoconus in association with cataract. The causative gene maps to the long arm of chromosome 15 but has not yet been identified. (Invest Ophthalmol Vis Sci