Dataset Information

Genetic Susceptibility, Diet Quality, and Two-Step Progression in Drusen Size.

ABSTRACT: Purpose:To investigate the relationship of growth in drusen size with genetic susceptibility and adherence to the alternate Mediterranean diet. Methods:Participants in this analysis had complete ocular, genetic, and dietary data with mean follow-up time of 10.2 years in the Age-Related Eye Disease database. Maximal drusen size was graded on an ordinal scale and two-step progression was determined. A genetic risk score using variants associated with advanced AMD and derived from a stepwise regression model yielded 11 variants in 8 genes. Adherence to the alternate Mediterranean diet was assessed using a nine-component score based on intake of vegetables, fruits, legumes, whole cereals, fish, meat, nuts, alcohol, and monounsaturated-to-saturated fatty acids ratio. Multivariate Cox proportional hazards models were used. Results:Among 3023 eligible eyes, 19% had drusen growth. In the stepwise selection, common and rare risk alleles for CFH Y402H, CFH rs1410996, CFH R1210C, C3 R102G, C3 K155Q, and ARMS2/HTRA1, as well as VEGF-A, TIMP3, NPLOC4, and HSPH1 variants were significantly associated with 2-step progression in drusen size, and the C2 E318D protective allele conferred decreased risk, adjusting for other covariates. A higher genetic risk score conferred a higher risk (hazard ratio per 1-unit increase, 2.68; 95% confidence interval, 2.23-3.23; P < 0.001), and a medium/high adherence to alternate Mediterranean diet score (4-9) tended to lower risk (hazard ratio, 0.83; 95% confidence interval, 0.68-0.99; P = 0.049), adjusting for all covariates. Conclusions:Genetic susceptibility was independently related to drusen growth. A Mediterranean-style diet with healthful nutrient-rich foods (fruits, vegetables, legumes and fish), may reduce enlargement of drusen, the hallmark of AMD.

SUBMITTER: Merle BMJ

PROVIDER: S-EPMC7405620 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature

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Genetic Susceptibility, Diet Quality, and Two-Step Progression in Drusen Size.

Merle Bénédicte M J BMJ Rosner Bernard B Seddon Johanna M JM

Investigative ophthalmology & visual science 20200501 5

<h4>Purpose</h4>To investigate the relationship of growth in drusen size with genetic susceptibility and adherence to the alternate Mediterranean diet.<h4>Methods</h4>Participants in this analysis had complete ocular, genetic, and dietary data with mean follow-up time of 10.2 years in the Age-Related Eye Disease database. Maximal drusen size was graded on an ordinal scale and two-step progression was determined. A genetic risk score using variants associated with advanced AMD and derived from a ...[more]

PMID: 32407518

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Project description:BACKGROUND:Adherence to a Mediterranean-type diet is linked to a lower risk of mortality and chronic disease, but the association with the progression of age-related macular degeneration (AMD) and genetic susceptibility is unknown. OBJECTIVE:We examined the association of adherence to the Mediterranean diet and genetic susceptibility with progression to advanced AMD. DESIGN:Among 2525 subjects in the AREDS (Age-Related Eye Disease Study), 1028 eyes progressed to advanced AMD over 13 y. Baseline data for demographic and behavioral covariates were collected by using questionnaires. Dietary data were collected from food-frequency questionnaires. The alternate Mediterranean diet (aMeDi) score (range: 0-9) was constructed from individual intakes of vegetables, fruit, legumes, whole grains, nuts, fish, red and processed meats, alcohol, and the ratio of monounsaturated to saturated fats. Ten genetic loci in 7 genes [complement factor H (CFH), age-related maculopathy susceptibility 2/high-temperature requirement A serine peptidase 1 (ARMS2/HTRA1), complement component 2 (C2), complement factor B (CFB), complement component 3 (C3), collagen type VIII ? 1 (COL8A1), and RAD51 paralog B (RAD51B)] were examined. Survival analysis was used to assess individual eyes for associations between incident AMD and aMeDi score, as well as interaction effects between aMeDi score and genetic variation on risk of AMD. RESULTS:A high aMeDi score (score of 6-9) was significantly associated with a reduced risk of progression to advanced AMD after adjustment for demographic, behavioral, ocular, and genetic covariates (HR: 0.74; 95% CI: 0.61, 0.91; P-trend = 0.007). The aMeDi score was significantly associated with a lower risk of incident advanced AMD among subjects carrying the CFH Y402H nonrisk (T) allele (P-trend = 0.0004, P-interaction = 0.04). The aMeDi score was not associated with AMD among subjects who were homozygous for the risk (C) allele. CONCLUSION:Higher adherence to a Mediterranean diet was associated with reduced risk of progression to advanced AMD, which may be modified by genetic susceptibility. This trial was registered at clinicaltrials.gov as NCT00594672.

Project description:Study hypothesis: CRC risk is affected by diet and by genetic polymorphisms leading to inter-individual variation in the metabolism of environmental carcinogens. Our first hypothesis is that these effects may combine to place certain individuals at greatly enhanced risk according to their diet. We shall examine how dietary factors known to affect CRC risk (including meats, fat, fruit and vegetables, cooking methods, dietary supplements and drugs) and genetic polymorphisms implicated in CRC (Glutathione S-transferase: GSTM1, GSTM3, GSTT1; N-acetyl transferase: NAT1, NAT2; and Cytochrome P450: CYP1A1, CYP2D6) combine to affect the prevalence of colorectal polyps, both adenomatous (the precursor lesion of CRC) and metaplastic. Our second hypothesis is that diets associated with increased risk (high red meat, low vegetable and low fibre consumption) may affect DNA damage markers which may be elevated in people with colorectal adenomas. We shall therefore examine the effect of diet on adduct rates (cross sectional) and adduct rates in people with and without colorectal adenomas. We shall examine malondialdehyde adduct rates in relation to anti-oxidant status and carboxymethyl adduct rates and k-ras mutation frequency in relation to meat consumption; and examine the effect of DNA repair enzyme (ATase) activity on any relationship found. In summary the aim of this population based study is to link dietary factors thought to be important in the genesis of colorectal polyps and cancer with genetic polymorphisms and DNA damage markers in rectal mucosa and in blood. Primary outcome(s): We shall perform cross-sectional and case-control analyses of the effect of diet and genetic polymorphisms on the prevalence of adenomatous and metaplastic polyps. Genetic polymorphisms will be examined in isolation and paired combinations and in groups stratified according to diet. We shall examine the effect of diet on MDA adduct rates (concentrating on foods relating to anti-oxidant status) and CBM adduct rates and k-ras mutations (concentrating on meat consumption and cooking methods) by categorical variables; and MDA and CBM adducts and k-ras mutation frequency in people with adenomatous polyps and polyp free controls (case-control). We shall examine the affect of ATase activity on any relationship found and ATase activity in people with adenomatous polyps and polyp free controls (case control). DNA will be stored for future analysis of as yet unrecognised polymorphisms which may be recognised as having a role in CRC. Samples taken from EPIC participants for adduct, ATase and k-ras measurement whose polyps are found to be metaplastic will be stored for possible future analysis: we shall investigate people with adenomatous polyps in the first instance as these are the precursors of colorectal cancer.

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Dataset Information

Genetic Susceptibility, Diet Quality, and Two-Step Progression in Drusen Size.

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Genetic Susceptibility, Diet Quality, and Two-Step Progression in Drusen Size.

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