著者

Nao Uchida Naonori Kumagai Kandai Nozu Xue Jun Fu Kazumoto Iijima Yoshiaki Kondo Shigeo Kure

出版者

東北ジャーナル刊行会

雑誌

The Tohoku Journal of Experimental Medicine (ISSN:00408727)

巻号頁・発行日

vol.240, no.3, pp.251-257, 2016 (Released:2016-11-29)

参考文献数

18

被引用文献数

2

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Alport syndrome is a progressive renal disease caused by mutations in COL4A3, COL4A4, and COL4A5 genes that encode collagen type IV alpha 3, alpha 4, and alpha 5 chains, respectively. Because of abnormal collagen chain, glomerular basement membrane becomes fragile and most of the patients progress to end-stage renal disease in early adulthood. COL4A5 mutation causes X-linked form of Alport syndrome, and two mutations in either COL4A3 or COL4A4 causes an autosomal recessive Alport syndrome. Recently, renin-angiotensin-aldosterone system (RAAS) blockade has been shown to attenuate effectively disease progression in Alport syndrome. Here we present three Japanese siblings and their father all diagnosed with autosomal recessive Alport syndrome and with different clinical courses, suggesting the importance of the early initiation of RAAS blockade. The father was diagnosed with Alport syndrome. His consanguineous parents and his wife were healthy. All three siblings showed hematuria since infancy. Genetic analysis revealed that they shared the same gene mutations in COL4A3 in a compound heterozygous state: c.2330G>A (p.Gly777Ala) from the mother and c.4354A>T (p.Ser1452Cys) from the father. Although RAAS blockade was initiated for the older sister and brother when their renal function was already impaired, it did not attenuate disease progression. In the youngest brother, RAAS blockade was initiated during normal renal function stage. After the initiation, his renal function has been normal with the very mild proteinuria to date at the age of 17 years. We propose that in Alport syndrome, RAAS blockade should be initiated earlier than renal function is impaired.

著者

Yuichiro Nishida Minako Iyadomi Yasuki Higaki Hiroaki Tanaka Yoshiaki Kondo Hiromi Otsubo Mikako Horita Megumi Hara Keitaro Tanaka

出版者

The Japanese Society of Internal Medicine

雑誌

Internal Medicine (ISSN:09182918)

巻号頁・発行日

vol.54, no.4, pp.359-366, 2015 (Released:2015-02-15)

参考文献数

45

被引用文献数

10 10

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Objective A lower frequency for the peroxisome proliferator-activated receptor γ coactivator 1α (PPARGC1A) Ser482 allele has been reported in elite-level endurance athletes among Caucasians, although this gene polymorphism has not been found to be associated with aerobic capacity in German, Dutch or Chinese populations. The purpose of the current study was to examine the associations between the Gly482Ser polymorphism and aerobic fitness in 112 Japanese middle-aged men. Methods The PPARGC1AGly482Ser polymorphism was identified according to a TaqMan® SNP genotyping assay. Habitual physical activity was objectively measured using an accelerometer. The lactate threshold (LT), an index of aerobic fitness, was measured based on a submaximal graded exercise test performed on an electric cycle ergometer. The association between the LT and the Gly482Ser polymorphism was assessed according to a multiple regression analysis and analysis of covariance, with adjustment for potential confounders (age, body mass index, cigarette smoking, physical activity level and regular exercise). Results A significant association was observed between the PPARGC1AGly482Ser polymorphism and LT, as carriers of the Ser482 had higher LT values than the Gly482 carriers. Conclusion The current results suggest that the PPARGC1ASer482 allele is associated with a higher aerobic capacity in Japanese middle-aged men.