title: Association of CC chemokine ligand 5 genotype with urinary albumin excretion in the non-diabetic Japanese general population: the Takahata study.
abstract: Albuminuria is an early marker of vascular damage, and its development in diabetic nephropathy is associated with genotype of inflammatory CC chemokine ligand 5 (CCL5). This study investigated whether the association of CCL5 and albuminuria is a general phenomenon. We characterized a Japanese population consisting of 2,749 non-diabetic individuals over 40 years in Takahata, Japan. The urine albumin-creatinine ratio (UACR) was obtained from morning spot urine. We genotyped SNPs within the CCL5 gene that displayed frequent minor allele frequencies in Japanese (i.e., rs2107538, rs2280789, rs3817655 and rs9909416). Assessment of possible association and linkage disequilibrium (LD) revealed that all four SNP genotypes are correlated significantly with UACR (P = 0.004-0.005), and these four SNPs variations showed an obvious consistency of genotypes by detecting almost complete linkage disequilibrium (D' = 1 and r (2) > 0.95). We found two exclusive haplotypes in the CCL5 gene (haplotype1: rs2107538G/rs2280789T/rs3817655T/rs9909416G, frequency 0.64 and haplotype2: rs2107538A/rs2280789C/rs3817655A/rs9909416A, frequency 0.35) among the population. A significant association with elevated UACR was identified with haplotype1 (P = 0.002). Homozygotes for haplotype1 displayed strikingly-elevated UACR (48.5 +/- 6.6 mg/g, n = 1,116) compared to the rest (28.6 +/- 1.6 mg/g, n = 1,530) (P = 0.001). In conclusion, these results suggested that genetic variation of CCL5 might be an important risk factor for albuminuria in the non-diabetic Japanese general population.
authors.affiliation: Department of Cardiology, Pulmonology, and Nephrology, Yamagata University School of Medicine, 2-2-2, Iida-Nishi, Yamagata, 990-9585, Japan. kkonta@med.id.yamagata-u.ac.jp.
authors.forename: Tsuneo
authors.initials: T
authors.lastname: Konta
authors.affiliation: HuBit Genomix Research Institute, Tokyo, Japan.
authors.forename: Mitsuru
authors.initials: M
authors.lastname: Emi
authors.affiliation: HuBit Genomix Research Institute, Tokyo, Japan.
authors.forename: Sayumi
authors.initials: S
authors.lastname: Toriyama
authors.affiliation: HuBit Genomix Research Institute, Tokyo, Japan.
authors.forename: Hideto
authors.initials: H
authors.lastname: Ariumi
authors.affiliation: HuBit Genomix Research Institute, Tokyo, Japan.
authors.forename: Miho
authors.initials: M
authors.lastname: Ishii
authors.affiliation: Department of Cardiology, Pulmonology, and Nephrology, Yamagata University School of Medicine, 2-2-2, Iida-Nishi, Yamagata, 990-9585, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Takasaki
authors.affiliation: Department of Cardiology, Pulmonology, and Nephrology, Yamagata University School of Medicine, 2-2-2, Iida-Nishi, Yamagata, 990-9585, Japan.
authors.forename: Ami
authors.initials: A
authors.lastname: Ikeda
authors.affiliation: Department of Cardiology, Pulmonology, and Nephrology, Yamagata University School of Medicine, 2-2-2, Iida-Nishi, Yamagata, 990-9585, Japan.
authors.forename: Kazunobu
authors.initials: K
authors.lastname: Ichikawa
authors.affiliation: Department of Cardiology, Pulmonology, and Nephrology, Yamagata University School of Medicine, 2-2-2, Iida-Nishi, Yamagata, 990-9585, Japan.
authors.forename: Yoko
authors.initials: Y
authors.lastname: Shibata
authors.affiliation: Department of Cardiology, Pulmonology, and Nephrology, Yamagata University School of Medicine, 2-2-2, Iida-Nishi, Yamagata, 990-9585, Japan.
authors.forename: Noriaki
authors.initials: N
authors.lastname: Takabatake
authors.affiliation: Department of Cardiology, Pulmonology, and Nephrology, Yamagata University School of Medicine, 2-2-2, Iida-Nishi, Yamagata, 990-9585, Japan.
authors.forename: Yasuchika
authors.initials: Y
authors.lastname: Takeishi
authors.affiliation: Department of Neurology, Hematology, Metabolism, Endocrinology and Diabetes, Yamagata University School of Medicine, Yamagata, Japan.
authors.forename: Takeo
authors.initials: T
authors.lastname: Kato
authors.affiliation: Department of Gastroenterology, Yamagata University School of Medicine, Yamagata, Japan.
authors.forename: Sumio
authors.initials: S
authors.lastname: Kawata
authors.affiliation: Department of Cardiology, Pulmonology, and Nephrology, Yamagata University School of Medicine, 2-2-2, Iida-Nishi, Yamagata, 990-9585, Japan.
authors.forename: Isao
authors.initials: I
authors.lastname: Kubota
mesh_terms: D000328:Adult; D000368:Aged; D000419:Albuminuria / Q000453:epidemiology / Q000235:genetics*; D044466:Asian People / Q000235:genetics; D018946:Chemokine CCL5 / Q000235:genetics*; D005838:Genotype; D006801:Humans; D007438:Introns; D007564:Japan / Q000453:epidemiology; D008024:Ligands; D008875:Middle Aged; D011401:Promoter Regions, Genetic; D012307:Risk Factors
chemical_list: C483024:CCL5 protein, human; D018946:Chemokine CCL5; D008024:Ligands