Primary open-angle glaucoma: Association with cholesterol 24s-hydroxylase (CYP46a1) gene polymorphism and plasma 24-hydroxycholesterol levels

Cynthia Fourgeux, Lucy Martine, Ingemar Björkhem, Ulf Diczfalusy, Corinne Joffre, Niyazi Acar, Catherine Creuzot-Garcher, Alain Bron, Lionel Bretillon
Invest. Ophthalmol. Vis. Sci.. 2009-12-01; 50(12): 5712
DOI: 10.1167/iovs.09-3655

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1. Invest Ophthalmol Vis Sci. 2009 Dec;50(12):5712-7. doi: 10.1167/iovs.09-3655.
Epub 2009 Jun 24.

Primary open-angle glaucoma: association with cholesterol 24S-hydroxylase
(CYP46A1) gene polymorphism and plasma 24-hydroxycholesterol levels.

Fourgeux C(1), Martine L, Björkhem I, Diczfalusy U, Joffre C, Acar N,
Creuzot-Garcher C, Bron A, Bretillon L.

Author information:
(1)Eye and Nutrition Research Group, UMR1129 FLAVIC (Flaveur, vision et
comportement du consommateur; Flavor, Vision, and Consumer Behavior), INRA
(French National Institute for Agricultural Research), Dijon, France.

PURPOSE: Genetics has made significant contributions to the study of glaucoma
over the past few decades. Cholesterol-24S-hydroxylase (CYP46A1) is a
cholesterol-metabolizing enzyme that is especially expressed in retinal ganglion
cells. CYP46A1 and its metabolic product, 24S-hydroxycholesterol, have been
linked to neurodegeneration. A single-nucleotide polymorphism (SNP) in the
CYP46A1 gene, designated as rs754203 and associated with Alzheimer disease, was
evaluated as a genetic risk factor for primary open-angle glaucoma (POAG), as
well as plasma 24S-hydroxycholesterol levels.
METHODS: The frequency of the CYP46*C and CYP46*T alleles was analyzed in 150
patients with POAG and 118 control subjects. Plasma 24S-hydroxycholesterol levels
were quantified. Sex, age, alleles, and genotype frequencies between patients
with POAG and control subjects were compared by using the chi(2) and Student’s
t-tests. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated by
logistic regression to assess the relative association between disease and age,
sex, and genotypes.
RESULTS: The frequency of the TT genotype was significantly higher in patients
with POAG than in control subjects (61.3% versus 48.3%, respectively, OR = 1.26;
95% CI = 1.006-1.574, P < 0.05). Plasma 24S-hydroxycholesterol levels did not
differ between control subjects and patients with POAG. The ratio of estimated
brain weight to liver volume as an estimate of the capacity of the human body to
synthesize and metabolize 24S-hydroxycholesterol was found to correlate to plasma
24S-hydroxycholesterol in control subjects and patients with POAG.
CONCLUSIONS: The rs754203 SNP in CYP46A1 was associated with a risk for POAG.
This polymorphism was not associated with changes in plasma
24S-hydroxycholesterol, highlighting that despite its retinal origin,
24S-hydroxycholesterol cannot be used as a biomarker for POAG.

DOI: 10.1167/iovs.09-3655
PMID: 19553612 [Indexed for MEDLINE]

Auteurs Bordeaux Neurocampus