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

Watanabe, Hirofumi; Goto, Shin; Miyashita, Akinori; Maruyama, Haruhiko; Wakasugi, Minako; Yokoseki, Akio; Kuwano, Ryozo; Narita, Ichiei

doi:10.1007/s10157-014-0969-y

Cited by 4 publications

(3 citation statements)

References 19 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Furthermore, seven patients had the p.Glu66Gln allele, which is known as a functional GLA variant [ 15 , 16 ] ( Table 1 ). The FD prevalence in patients with CKD Stage 5D was 0.06%, which corroborated the previous report [ 11 ].…”

Section: Resultsmentioning

confidence: 99%

Screening of Fabry disease in patients with chronic kidney disease in Japan

Nagata

Nasu

Kaida

et al. 2021

Nephrology Dialysis Transplantation

View full text Add to dashboard Cite

Background Fabry disease (FD), an X-linked lysosomal storage disorder caused by a deficiency in alfa-galactosidase A (α-Gal A) activity due to mutations in the GLA gene, has a prevalence of 0–1.69% in patients undergoing haemodialysis; however, its prevalence in patients with chronic kidney disease (CKD) Stages 1–5 is unknown. Methods Serum α-Gal A activity analysis and direct sequencing of GLA were used to screen for FD in 2122 male patients with CKD, including 1703 patients with CKD Stage 5D and 419 with CKD Stages 1–5. The correlation between serum α-Gal A activity and confounding factors in patients with CKD Stages 1–5 was evaluated. Results FD prevalence rates in patients with CKD Stage 5D and CKD Stages 1–5 were 0.06% (1/1703) and 0.48% (2/419), respectively. A patient with CKD Stage 5D exhibited a novel GLA mutation, p.Met208Arg, whereas two patients with CKD Stages 1–5 had c.370delG and p.Met296Ile. p. Met208Arg caused moderate structural changes in the molecular surface region near the substituted amino acid residue but did not affect the catalytic residues Asp170 and Asp231 in α-Gal A. Serum α-Gal A activity in patients with CKD Stages 1–5 was inversely correlated with age (P < 0.0001) but directly correlated with estimated glomerular filtration rate (P < 0.0001). Conclusions FD prevalence was much higher in male patients with CKD Stages 1–5 than in those with CKD Stage 5D. FD screening in patients with CKD Stages 1–5 may improve patient survival, decreasing the number of patients with CKD Stage 5D.

show abstract

Section: Resultsmentioning

confidence: 99%

Screening of Fabry disease in patients with chronic kidney disease in Japan

Nagata

Nasu

Kaida

et al. 2021

Nephrology Dialysis Transplantation

View full text Add to dashboard Cite

show abstract

“…The present cross-sectional study analyzed a subgroup of the Project in Sado for Total Health (PROST), a hospital-based cohort study in Sado City, Niigata Prefecture, Japan ( http://square.umin.ac.jp/prost/ ). The PROST began in June 2008 and is an ongoing cohort study targeting outpatients (age ≥20 years) of Sado General Hospital [ 21 ]. In the current study, 1,272 individuals registered with the PROST before November 19, 2012 were analyzed.…”

Section: Methodsmentioning

confidence: 99%

Elevated C-Reactive Protein Is Associated with Cognitive Decline in Outpatients of a General Hospital: The Project in Sado for Total Health (PROST)

Watanabe¹,

Kitamura²,

Nakamura³

et al. 2016

Dement Geriatr Cogn Disord Extra

Self Cite

View full text Add to dashboard Cite

Background/Aims: We aimed to determine whether the concentration of serum C-reactive protein (CRP) is associated with cognitive function in an adult Japanese population. Methods: Participants of this cross-sectional study were from a subgroup of the Project in Sado for Total Health (PROST; n = 454; mean age, 70.5 years). The cognitive state was evaluated using the Mini-Mental State Examination (MMSE), and those with an MMSE score <24 were considered ‘cognitively declined'. Concentrations of serum high-sensitivity CRP were measured. Multiple logistic regression analysis was used to calculate odds ratios (ORs) for cognitive decline, adjusting for the covariates of age, sex, BMI, disease history, and APOE allele. Results: Of the 454 participants, 94 (20.7%) were cognitively declined. Relative to the lowest (first) quartile of CRP concentration, adjusted ORs were 1.29 (95% CI 0.61-2.75) for the second, 1.78 (95% CI 0.82-3.86) for the third, and 3.05 (95% CI 1.45-6.42) for the highest (fourth) quartiles (p for trend = 0.018). When data were stratified by sex, the association between CRP concentration and cognitive decline was observed only in women. Conclusion: Our findings suggest an association between higher CRP concentration and lower cognitive function. Chronic inflammation may affect cognitive function in adults, in particular women.

show abstract

“…In the present case, both PAS-positive vacuolated cardiomyocytes and small number of zebra bodies were observed in LV myocardium, but no accumulation of Gb3, indicating that those histological changes were not associated with Fabry disease. A recent study showed that the frequency of the E66Q allele was not different between hemodialysis patients and the general Japanese population [ 18 ]. Therefore, thorough genetic analysis is needed to perform differential diagnosis of Fabry disease.…”

Section: Case Presentationmentioning

confidence: 99%

Familial hypertrophic obstructive cardiomyopathy with the GLA E66Q mutation and zebra body

Oikawa

Sakamoto

Kobayashi

et al. 2016

BMC Cardiovasc Disord

View full text Add to dashboard Cite

BackgroundFabry disease is caused by mutations in the α-galactosidase A (GLA) gene, which is located in X-chromosome coding for the lysosomal enzyme of GLA. Among many gene mutations, E66Q mutation is under discussion for its pathogenicity because there is no clinical report showing pathological evidence of Fabry disease with E66Q mutation.Case presentationA 65-year-old Japanese female was referred to our hospital for chest discomfort on effort. Transthoracic echocardiography showed severe left ventricular (LV) hypertrophy with LV outflow obstruction. Maximum LV outflow pressure gradient was 87 mmHg, and Valsalva maneuver increased the pressure gradient up to 98 mmHg. According to medical interview, one of her younger sister and a nephew died suddenly at age 42 and 36, respectively. Another younger sister also presented LV hypertrophy with outflow obstruction. Maximum LV outflow pressure gradient was 100 mmHg, and the E66Q mutation was detected similar to the case. Endomyocardial biopsy specimens presented vacuolation of cardiomyocytes, in which zebra bodies were detected by electron microscopic examination. Although the enzymatic activity of GLA was within normal range, the c. 196G>C nucleotide change, which lead to the E66Q mutation of GLA gene, was detected. We initially diagnosed her as cardiac Fabry disease based on the findings of zebra body. However, immunostaining showed few deposition of globotriaosylceramide in left ventricular myocardium, and gene mutations in the disease genes for hypertrophic cardiomyopathy (HCM), MYBPC3 and MYH6, were detected. Although the pathogenicity of the E66Q mutation cannot be ruled out, hypertrophic obstructive cardiomyopathy (HOCM) was more reasonable to explain the pathophysiology in the case.ConclusionsThis is the confusable case of HOCM with Fabry disease with the GLA E66Q mutation. We have to take into consideration the possibility that some patients with the E66Q mutation may have similar histological findings of Fabry disease, and should be examed the possibility for harboring gene mutations associated with HCM.

show abstract

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

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

Cited by 4 publications

References 19 publications

Screening of Fabry disease in patients with chronic kidney disease in Japan

Screening of Fabry disease in patients with chronic kidney disease in Japan

Elevated C-Reactive Protein Is Associated with Cognitive Decline in Outpatients of a General Hospital: The Project in Sado for Total Health (PROST)

Familial hypertrophic obstructive cardiomyopathy with the GLA E66Q mutation and zebra body

Contact Info

Product

Resources

About