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Role of the p.E66Q variant of GLA in the progression of chronic kidney disease

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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).


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.


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 m2, P = 0.69).


This study indicated that the p.E66Q variant of GLA does not affect the progression of CKD.

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We thank Ms. Hiroko Aita for technical assistance. We are indebted to the patients, nurses, medical staff, and physicians who supported this study. This work was supported by a Grant-in-Aid for Scientific Research (B) from the Ministry of Education, Science and Culture of Japan (23390223) (H.M.), and by a Grant-in-Aid for Project in Sado for Total Health (PROST) from the Ministry of Education, Culture, Sports, Science and Technology of Japan.

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Correspondence to Ichiei Narita.

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Watanabe, H., Goto, S., Miyashita, A. et al. Role of the p.E66Q variant of GLA in the progression of chronic kidney disease. Clin Exp Nephrol 19, 225–230 (2015).

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