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CFH gene variant, Y402H, and smoking, body mass index, environmental associations with advanced age-related macular degeneration.

Abstract

OBJECTIVES

We tested the hypothesis that modifiable lifestyle factors alter the genetic susceptibility associated with a common coding variant in the complement factor H (CFH) gene, Y402H, for the leading cause of blindness among the elderly, age-related macular degeneration (AMD).

METHODS

In this case-control association analysis, Caucasian participants in the multicenter Age-Related Eye Disease Study with advanced AMD (n = 574 cases) or no AMD (n = 280 controls) were evaluated. AMD status was determined by grading of fundus photographs. Risk factors including cigarette smoking and body mass index (BMI) were assessed and DNA specimens were genotyped for the variant in the CFH gene. Unconditional logistic regression analyses were performed. Attributable risks and multivariable AMD risk scores were calculated.

RESULTS

The number of risk alleles for Y402H was associated with advanced AMD, with odds ratios (OR) of 2.7 (95% confidence interval (CI) 1.8-3.8) for the CT heterozygous genotype and OR 7.4 (4.7-11.8) for the homozygous CC risk genotype, after controlling for demographic and behavioral risk factors. Current cigarette smoking (OR 5.1) and high BMI > or =30 (OR 2.1) were independently related to AMD, controlling for genotype. The association between AMD and BMI varied dependent on genotype (P interaction = 0.006 for the CT vs. TT genotype). The CC genotype plus higher BMI (OR 5.9) or smoking (OR 10.2) conferred the greatest risks. Gene plus environment risk scores provided an area under the receiver operating characteristic (ROC) curve of 0.70-0.75.

CONCLUSIONS

Genetic and environmental factors are independently related to advanced AMD, and modifiable factors alter genetic susceptibility. The AMD risk score identifies a highly susceptible population.

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  • Authors+Show Affiliations

    ,

    Epidemiology Unit, Massachusetts Eye and Ear Infirmary, Harvard Medical School, 243 Charles Street, Boston, MA 02114, USA. Johanna_Seddon@meei.harvard.edu

    , ,

    Source

    Human heredity 61:3 2006 pg 157-65

    MeSH

    Aged
    Aged, 80 and over
    Aging
    Body Mass Index
    Case-Control Studies
    Complement Factor H
    Female
    Genetic Predisposition to Disease
    Genotype
    Humans
    Macular Degeneration
    Male
    Middle Aged
    Polymorphism, Genetic
    Risk Factors
    Smoking

    Pub Type(s)

    Journal Article
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't

    Language

    eng

    PubMed ID

    16816528

    Citation

    Seddon, Johanna M., et al. "CFH Gene Variant, Y402H, and Smoking, Body Mass Index, Environmental Associations With Advanced Age-related Macular Degeneration." Human Heredity, vol. 61, no. 3, 2006, pp. 157-65.
    Seddon JM, George S, Rosner B, et al. CFH gene variant, Y402H, and smoking, body mass index, environmental associations with advanced age-related macular degeneration. Hum Hered. 2006;61(3):157-65.
    Seddon, J. M., George, S., Rosner, B., & Klein, M. L. (2006). CFH gene variant, Y402H, and smoking, body mass index, environmental associations with advanced age-related macular degeneration. Human Heredity, 61(3), pp. 157-65.
    Seddon JM, et al. CFH Gene Variant, Y402H, and Smoking, Body Mass Index, Environmental Associations With Advanced Age-related Macular Degeneration. Hum Hered. 2006;61(3):157-65. PubMed PMID: 16816528.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - CFH gene variant, Y402H, and smoking, body mass index, environmental associations with advanced age-related macular degeneration. AU - Seddon,Johanna M, AU - George,Sarah, AU - Rosner,Bernard, AU - Klein,Michael L, Y1 - 2006/06/30/ PY - 2006/04/13/received PY - 2006/04/14/accepted PY - 2006/7/4/pubmed PY - 2006/10/27/medline PY - 2006/7/4/entrez SP - 157 EP - 65 JF - Human heredity JO - Hum. Hered. VL - 61 IS - 3 N2 - OBJECTIVES: We tested the hypothesis that modifiable lifestyle factors alter the genetic susceptibility associated with a common coding variant in the complement factor H (CFH) gene, Y402H, for the leading cause of blindness among the elderly, age-related macular degeneration (AMD). METHODS: In this case-control association analysis, Caucasian participants in the multicenter Age-Related Eye Disease Study with advanced AMD (n = 574 cases) or no AMD (n = 280 controls) were evaluated. AMD status was determined by grading of fundus photographs. Risk factors including cigarette smoking and body mass index (BMI) were assessed and DNA specimens were genotyped for the variant in the CFH gene. Unconditional logistic regression analyses were performed. Attributable risks and multivariable AMD risk scores were calculated. RESULTS: The number of risk alleles for Y402H was associated with advanced AMD, with odds ratios (OR) of 2.7 (95% confidence interval (CI) 1.8-3.8) for the CT heterozygous genotype and OR 7.4 (4.7-11.8) for the homozygous CC risk genotype, after controlling for demographic and behavioral risk factors. Current cigarette smoking (OR 5.1) and high BMI > or =30 (OR 2.1) were independently related to AMD, controlling for genotype. The association between AMD and BMI varied dependent on genotype (P interaction = 0.006 for the CT vs. TT genotype). The CC genotype plus higher BMI (OR 5.9) or smoking (OR 10.2) conferred the greatest risks. Gene plus environment risk scores provided an area under the receiver operating characteristic (ROC) curve of 0.70-0.75. CONCLUSIONS: Genetic and environmental factors are independently related to advanced AMD, and modifiable factors alter genetic susceptibility. The AMD risk score identifies a highly susceptible population. SN - 0001-5652 UR - https://www.unboundmedicine.com/medline/citation/16816528/CFH_gene_variant_Y402H_and_smoking_body_mass_index_environmental_associations_with_advanced_age_related_macular_degeneration_ L2 - https://www.karger.com?DOI=10.1159/000094141 DB - PRIME DP - Unbound Medicine ER -