Possible pathologic involvement of receptor for advanced glycation end products (RAGE) for development of encapsulating peritoneal sclerosis in Japanese CAPD patients.
Encapsulating peritoneal sclerosis (EPS) is a serious complication of PD. The cause(s) of EPS are unknown but may include peritonitis and long duration of PD treatment. However, EPS may also develop in some patients without a history of peritonitis or with rather short duration of PD therapy. It has been suggested that an increasing peritoneal solute transport rate (PSTR) as a function of time on PD treatment is a risk factor for EPS development after transfer to hemodialysis, and that high PSTR is associated with an increased peritoneal microvessels surface area. Other putative mechanisms might include advanced glycated end products (AGE) and their receptors, RAGE. The purpose of this study was to investigate genetic variations in PD patients developing EPS in comparison to PD patients without EPS. SNPs in genes related to angiogenesis as well as RAGE were analyzed. Twenty patients (M/F: 12/8, mean age at start of PD 42.2 years, mean duration of PD 8.4 years) who were diagnosed as EPS during the period 1982 - 2002 at Jikei University Hospital and a matched control group (n = 20) of nonEPS PD patients were studied. The following 5 SNPs were analyzed: VEGF 936 C/T, ecNOS -786 T/C, 298 Glu/Asp, and RAGE -374 T/A, and -429 T/C. The SNPs were analyzed by the pyrosequencing method. The C allele (T/C and C/C) in the RAGE -429T/C genotype was not found in any of the EPS patients (EPS, T/T: 20/20 (100%), nonEPS, T/T: 15/20 (75%), T/C: 4/20 (20%), C/C: 1/2 0(5%), nonC allele vs C allele, p = 0.013), although every allele was found in other SNPs. We conclude that these preliminary data show that whereas genotypes directly related to angiogenesis did not differ between EPS and nonEPS patients, it is noteworthy that no patients in the EPS group had a C allele in the RAGE -429T/C genotype. This might indicate a possible genetic contribution to the development of EPS that is related to RAGE.
Numata
M
M
Department of Internal Medicine, Jikei University School of Medicine, Tokyo, Japan. mnumata@jikei.ac.jp
Nakayama
M
M
Hosoya
T
T
Hoff
C M
CM
Holmes
C J
CJ
Schalling
M
M
Nordfors
L
L
Lindholm
B
B
D000328:Adult; D000368:Aged; D005260:Female; D005838:Genotype; D017127:Glycation End Products, Advanced / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D019001:Nitric Oxide Synthase / Q000235:genetics; D052250:Nitric Oxide Synthase Type III; D010531:Peritoneal Dialysis, Continuous Ambulatory / Q000009:adverse effects*; D010532:Peritoneal Diseases / Q000235:genetics* / Q000473:pathology; D010537:Peritoneum / Q000473:pathology; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000235:genetics*; D012598:Sclerosis; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics
D017127:Glycation End Products, Advanced; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic; D042461:Vascular Endothelial Growth Factor A; C496314:NOS3 protein, human; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III