Homocysteine, B Vitamins, MTHFR Genotype, and Incident Age-related Macular Degeneration.
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ABSTRACT:
SUBMITTER: Christen WG
PROVIDER: S-EPMC6022858 | biostudies-literature | 2018 May
REPOSITORIES: biostudies-literature
Publications
Homocysteine, B Vitamins, MTHFR Genotype, and Incident Age-related Macular Degeneration.
Christen William G WG Chasman Daniel I DI Cook Nancy R NR Chiuve Stephanie E SE Ridker Paul M PM Buring Julie E JE
Ophthalmology. Retina 20180501 5
Similar Datasets
Project description:PurposeTo describe associations of serum lipid levels and lipid pathway genes to the incidence of age-related macular degeneration (AMD).DesignMeta-analysis.Methodssetting: Three population-based cohorts. population: A total of 6950 participants from the Beaver Dam Eye Study (BDES), Blue Mountains Eye Study (BMES), and Rotterdam Study (RS). observation procedures: Participants were followed over 20 years and examined at 5-year intervals. Hazard ratios associated with lipid levels per standard deviation above the mean or associated with each additional risk allele for each lipid pathway gene were calculated using random-effects inverse-weighted meta-analysis models, adjusting for known AMD risk factors. main outcome measures: Incidence of AMD.ResultsThe average 5-year incidences of early AMD were 8.1%, 15.1%, and 13.0% in the BDES, BMES, and RS, respectively. Substantial heterogeneity in the effect of cholesterol and lipid pathway genes on the incidence and progression of AMD was evident when the data from the 3 studies were combined in meta-analysis. After correction for multiple comparisons, we did not find a statistically significant association between any of the cholesterol measures, statin use, or serum lipid genes and any of the AMD outcomes in the meta-analysis.ConclusionIn a meta-analysis, there were no associations of cholesterol measures, history of statin use, or lipid pathway genes to the incidence and progression of AMD. These findings add to inconsistencies in earlier reports from our studies and others showing weak associations, no associations, or inverse associations of high-density lipoprotein cholesterol and total cholesterol with AMD.
| S-EPMC4138281 | biostudies-literature
Project description:PurposeExamine potential effects of sunlight exposure, hair color, eye color, and selected gene single-nucleotide polymorphisms (SNPs) on incidence of AMD.MethodsSubjects participated in up to five examinations over a 20-year period. Eye color, self-reported hair color as a teenager, and sunlight exposure were ascertained at the baseline examination. Presence and severity of AMD and its lesions were determined via fundus photographs. Genetic data were available on a subset of participants. The SNPs CFH Y402H rs1061170 and ARMS2 A69S rs10490924 were used to analyze genetic risk of AMD; OCA2 rs4778241 and HERC2 rs12913832 represented genetic determinants of eye color.ResultsIncidence of early AMD was higher in blond/red-haired persons compared with brown/black-haired persons (hazard ratio [HR] 1.25, P = 0.02) and in persons with high sun exposure in their thirties (HR 1.41, P = 0.02). However, neither was significant after adjustment for multiple comparisons. Eye (HR 1.36, P = 0.006) and hair color (HR 1.42, P = 0.003) were associated with incidence of any retinal pigmentary abnormalities (RPAs). Both remained significant after adjustment for multiple comparisons. Neither presence of alleles for light-colored eyes nor those associated with high risk of late AMD altered the association of eye or hair color with early AMD. None of the characteristics studied were significantly associated with late AMD.ConclusionsModest associations of eye color, hair color, and HERC2 genotype with any RPAs were found. Genes for AMD did not affect these associations. Eye color phenotype was more strongly associated with outcomes than HERC2 or OCA2 genotype.
| S-EPMC4165367 | biostudies-literature
Project description:To evaluate whether Chlamydia (C.) infections are associated with age-related macular degeneration (AMD) and to assess if this association is influenced by the complement factor H (CFH) Y402H or the high temperature requirement A serine peptidase 1 (HTRA1) rs11200638 risk genotypes.One hundred ninety-nine AMD patients with early and late forms of the disease and 100 unaffected controls, at least 50 years old were included in the study. Patients in the AMD and control groups were selected based on known CFH Y402H variant genotype status (one third homozygous CC, one third heterozygous CT, and one third wild-type TT). Plasma from all patients and controls was tested for C. pneumoniae, C. trachomatis, and C. psittaci IgG seropositivity using a micro-immunofluorescent assay to establish previous infection status. Assays were conducted blind to risk genotypes and the results analyzed using univariate and multivariate (logistic regression) analysis.IgG seropositivity to C. pneumoniae was most prevalent (69.2%, n=207), followed by C. trachomatis (7.4%, n=22) and C. psittaci (3.3%, n=10). No association was found between each of the three Chlamydia species IgG seropositivity and AMD status or severity (early/late). There was also no significant association between Chlamydia species IgG seropositivity and AMD status or severity, in patients carrying at least one CFH Y402H risk allele (C) or HTRA1 rs11200638 risk allele (A), with univariate or logistic regression analysis.Chlamydia infection status does not appear to be associated with AMD status or severity. The presence of CFH Y402H and HTRA1 rs11200638 risk genotypes does not alter this negative association.
| S-EPMC3258520 | biostudies-literature
Project description:B vitamins may protect against age-related macular degeneration (AMD). We evaluated the associations of dietary intake and serum vitamins with the incidence of advanced AMD in the Alienor study. The Alienor study is a prospective population-based cohort of 963 residents of Bordeaux, France, who were 73 years or older at baseline (2006-2008). Examinations were performed every two years over an eight-year period. The incidence of AMD is based on retinal fundus photographs and spectral-domain optical coherence tomography examinations. Among the 861 included participants, 93 developed incident AMD during a median follow-up time of 9.8 years. Participants with normal serum folate (≥10 nmol/L) significantly had a 51% reduced risk for AMD in the fully adjusted Cox model (HR, 0.49 [95% CI, 0.25-0.95], p = 0.036). Participants with a higher dietary intake of B5 and B6 vitamins had a lower risk for developing AMD of up to 28% (HR, 0.72 for 1-SD increase [0.53-0.99], p = 0.049; HR, 0.90 [0.81-0.99], p = 0.049, respectively). This cohort study of older adults suggests a strong association between a normal serum folate status, a high dietary intake of B5 and B6 and a lower risk for developing advanced AMD. Adopting a healthy diet rich in B vitamins may help to reduce vision loss due to AMD.
| S-EPMC9318446 | biostudies-literature
Project description:PurposeWe sought to determine whether genotype is associated with rate of growth of geographic atrophy (GA) in eyes with age-related macular degeneration (AMD).DesignProspective analysis of participants in a randomized controlled clinical trial.ParticipantsWe included 114 eyes of 114 participants in the Age-Related Eye Disease Study (AREDS).MethodsFundus photographs from AREDS participants with GA from whom a DNA specimen had been obtained and serial photographs had been taken over a minimum of 2 years were evaluated for progression as determined by change in cumulative area of GA. All fundus photographs were scanned, digitized, and centrally graded longitudinally for area of GA. The relationship of GA progression with previously identified genetic variants associated with AMD was assessed.Main outcome measuresGenotype frequencies and change in cumulative area of GA.ResultsThe mean growth rate of GA for the 114 eyes was 1.79 mm(2)/year (range, 0.17-4.76). No association between growth rate and genotype was present for variants in the CFH, C2, C3, APOE, and TLR3 genes. For the single nucleotide polymorphism rs10490924 in LOC387715/ARMS2, there was a significant association of GA growth rate, both adjusted and unadjusted for initial lesion size, with the homozygous risk genotype as compared with the homozygous nonrisk genotype (unadjusted P = 0.002; Bonferroni-corrected P = 0.014) and for allelic association (Bonferroni-corrected P value = 0.011). Analyses of other measures of GA progression (progression to central GA from extrafoveal GA and development of bilateral GA in those initially with unilateral GA) showed no statistically significant association between progression and the LOC387715/ARMS2/HTRA1 genotype.ConclusionsGrowth rates of GA calculated from digitized serial fundus photographs showed no association with variants in the CFH, C2, C3, APOE, or TLR3 genes. There was a nominally significant association with the LOC387715/ARMS2/HTRA1 genotype, although this finding was not supported by analyses of secondary measures of GA progression. Replication in other populations is needed to establish the existence of an association.
| S-EPMC2904435 | biostudies-literature
Project description:CLINICAL QUESTION:Is there any new knowledge about the pathogenesis and treatment of age-related macular degeneration (AMD)? RESULTS:We now understand better the biochemical and pathological pathways involved in the genesis of AMD. Treatment of exudative AMD is based on intravitreal injection of new antivascular endothelial growth factor drugs for which there does not yet exist a unique recognized strategy of administration. No therapies are actually available for atrophic AMD, despite some experimental new pharmacological approaches. IMPLEMENTATION:strategy of administration, safety of intravitreal injection.
| S-EPMC3102591 | biostudies-literature
Project description: Not available
| S-EPMC1125371 | biostudies-literature
Project description:Contrasting results have been reported regarding the associations between plasma total homocysteine (tHcy) and B vitamin levels and age-related macular degeneration (AMD) risk. Thus, we aimed to systematically evaluate these associations. Relevant case control studies in English were identified via a thorough search of the PubMed, Medline, and Embase databases from inception to June 2014. The results were pooled using Review Manager 5.2.1. Eleven studies (including 1072 cases and 1202 controls) were eligible for analysis of tHcy levels; additionally, 3 studies (including 152 cases and 98 controls) were eligible for analysis of folic acid and vitamin B12 levels. The cumulative results demonstrated that the plasma tHcy level among the AMD cases was 2.67 μmol/L (95% confidence interval [CI], 1.60-3.74) higher than that among the controls. In contrast, the vitamin B12 level among the AMD cases was 64.16 pg/mL (95% CI, 19.32-109.00) lower than that among the controls. Subgroup analyses showed that the folic acid level was 1.66 ng/mL (95% CI, 0.10-3.21) lower for the wet type. Together, the results demonstrated that AMD is associated with elevated tHcy levels and decreased vitamin B12 levels. Plasma tHcy may act as a modulator of the risk for AMD based on the current evidence.
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Project description:This SuperSeries is composed of the following subset Series: GSE28002: Gene expression of the whole mouse eye GSE28032: Epigenetic Regulation of IL17RC in Age-related Macular Degeneration (MeDIP-chip) Refer to individual Series
2011-03-22 | E-GEOD-28033 | biostudies-arrayexpress
Project description:Prospective data to examine the association of homocysteine with age-related macular degeneration (AMD) are limited. We examined the prospective relation of plasma homocysteine level and AMD in a large cohort of apparently healthy women.We evaluated the relationship between baseline levels of plasma homocysteine and incident AMD among 27,479 female health professionals aged 40 years or older. Main outcome measures were total AMD, defined as self-report documented by medical record evidence of an initial diagnosis after randomization, and visually significant AMD, defined as confirmed incident AMD with visual acuity 20/30 or worse attributable to this condition.During an average 10 years of follow-up, a total of 452 cases of AMD, including 182 cases of visually significant AMD, were documented. Women in the highest versus lowest quartile of plasma homocysteine had modestly, but statistically non-significant, increased risks of total AMD (hazard ratio, HR, 1.24, 95% confidence interval, CI, 0.95-1.63; p for trend 0.07) and visually significant AMD (HR 1.41, 95% CI 0.92-2.17; p for trend 0.052) in age- and treatment-adjusted analyses.These prospective data from a large cohort of apparently healthy women do not support a strong role for homocysteine in AMD occurrence.
| S-EPMC4363940 | biostudies-literature