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Genes and age-related macular degeneration

Study
Results
Interactions with lifestyle factors
Comment

Bandolier continues its journey into ever-harder tasks by trying to get its neurone wrapped around a genetics paper. In the usual course of events our neurone may have given up, except for the importance of the topic, age related macular degeneration (AMD). The paper includes both a meta-analysis and interactions with lifestyle factors [1] that makes it worth pursuing.

Study

Participants in two major US epidemiological studies were involved - the US Nurses Study and the Health professionals Follow Up Study, which between them originally enrolled about 170,000 healthcare professionals for long-term follow up. About 50,000 of these who had provided blood samples were used as the study base. Briefly, participants were asked about a diagnosis of AMD, with permission to review medical records. A diagnosis of AMD was confirmed by standard methods. For each case two or three controls were selected, within one year of age and with an eye examination within the previous two years.

DNA assays were used to explore for one known gene (CFH Y402H) and one locus for a hypothetical, but unknown, gene (LOC387715 A69S).

Results

The study group had 457 cases of AMD (293 dry AMD, 164 neovascular AMD) and 1,071 controls. AMD cases were associated with higher rates of obesity, smoking, and alcohol consumption, and lower intake of fruit and vegetables.

The incidence rate ratios for each of the genomes of each gene are shown in Figure 1. People homozygous for the high risk variants of both genes (SS and HH) had a 50 times (95% CI 10 to 240) greater risk of AMD. The attributable fraction for each high risk allele was 45% for CFH Y402H, 34% for LOC387715 A69S, and 63% for both genes together.



Figure 1: Incidence rate ratio for AMD according to presence of high risk alleles of CFH Y402H and LOC387715 A69S





Meta-analysis of nine studies of the association between CFH Y402H variant and AMD showed odds ratios of about 2 for heterozygotes and 6 for homozygotes. For LOC387715 A69S heterozygotes and homozygotes the odds ratios were about 2 and 7.

Interactions with lifestyle factors

Having a BMI ≥30 and being a current smoker doubled the risk of AMD for all most all genotypes of both genes. The most important lifestyle interactions with genetics were obesity and smoking for high risk homozygotes. For instance, for high risk homozygotes of CFH Y402H geneotype, being overweight trebled the risk, and current smoking doubled it. For high risk homozygotes of LOC387715 A69S genotype current smoking quadrupled the risk.

Comment

Bandolier is fully aware that any gene jockeys reading this poor account of some stupendous work might fume at the inadequate treatment of their arcane arts. It is not an easy paper to read. But the message is important, and in the end simple.

If you happen to be one of the folk with two copies of the high risk variant of each of the two genes, your risk of AMD developing is very much higher than the average in the population. But the message is also that the risk is multiplied even more by an unhealthy lifestyle. For those at risk, lifestyle is the most important thing. This you can change: you can't change your genes.

For those who moan that we don't know if we have the high risk genotype, or who are prepared to gamble on not having it, Bandolier reminds you that an unhealthy lifestyle is stupid for any number of other reasons.

It is an interesting example of how genetics and environment conspire to produce very bad results in some people - the why me? Question answered.

Reference:

  1. DA Schaumberg et al. A prospective study of 2 major age-related macular degeneration susceptibility alleles and interactions with modifiable risk factors, Archives of Ophthalmology 2007 125: 55-62.

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