Role of the p.E66Q variant of GLA in the progression of chronic kidney disease.
BACKGROUND
The p.E66Q variant of the α-galactosidase A gene (GLA) is frequently found during screening for Fabry disease in dialysis patients in Japan. However, recent reports suggest that the p.E66Q variant is not a disease-causing mutation but is a risk factor for cerebral small-vessel occlusion. To evaluate the role of the p.E66Q in the progression of renal diseases, we performed a genetic association study in patients with chronic kidney disease (CKD).


METHODS
In this study, we enrolled 1651 chronic hemodialysis and 941 non-dialysis patients who attended medical institutions in the Niigata Prefecture, Japan. The frequency of the p.E66Q allele was compared between hemodialysis and non-dialysis patients, with data from a previously published study of Japanese male newborns. In addition, we compared estimated glomerular filtration rates (eGFR) in the presence or absence of the p.E66Q variant in non-dialysis patients.


RESULTS
Of the 2233 alleles in hemodialysis and 1447 alleles in non-dialysis patients, 21 and nine harbored p.E66Q, respectively. However, p.E66Q allele frequencies did not differ between the two patient groups (0.90 versus 0.62 %, P = 0.35), and no significant difference in p.E66Q allele frequency was observed between male hemodialysis patients and the general Japanese population (0.52 versus 0.63 %, P = 0.67). Moreover, eGFR did not significantly differ between non-dialysis patients with the p.E66Q variant and patients with the wild-type allele (65.5 ± 10.7 versus 62.7 ± 16.6 mL/min/1.73 m(2), P = 0.69).


CONCLUSIONS
This study indicated that the p.E66Q variant of GLA does not affect the progression of CKD.
Division of Clinical Nephrology and Rheumatology, Niigata University Graduate School of Medical and Dental Sciences, 1-757 Asahimachi-dori, Chuo-ku, Niigata, Niigata, 951-8510, Japan.
Hirofumi
H
Watanabe
Shin
S
Goto
Akinori
A
Miyashita
Hiroki
H
Maruyama
Minako
M
Wakasugi
Akio
A
Yokoseki
Ryozo
R
Kuwano
Ichiei
I
Narita
D000368:Aged; D016022:Case-Control Studies; D018450:Disease Progression; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D005838:Genotype; D005919:Glomerular Filtration Rate; D006801:Humans; D007564:Japan; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011446:Prospective Studies; D006435:Renal Dialysis; D051436:Renal Insufficiency, Chronic / Q000235:genetics* / Q000503:physiopathology / Q000628:therapy; D000519:alpha-Galactosidase / Q000235:genetics*
D000519:alpha-Galactosidase