title: Polymorphisms of genes involved in lipid metabolism and risk of chronic kidney disease in Japanese - cross-sectional data from the J-MICC study.
abstract: BACKGROUND
  Chronic kidney disease (CKD) is known to be one of the causes of cardiovascular disease and end-stage renal disease. Among the several treatable risk factors of CKD, that of dyslipidemia is relatively controversial. To clarify the association of polymorphisms in genes involved in lipid metabolism with the risk of CKD in the Japanese population, we used cross-sectional data from the Japan Multi-Institutional Collaborative Cohort (J-MICC) Study.
  
  
  METHODS
  A total of 3,268 men and women, aged 35-69 years, were selected from J-MICC Study participants for inclusion in this study. Twenty-eight candidate single nucleotide polymorphisms (SNPs) were selected in 17 genes associated with the risk of lipid metabolism disorders, and genotyping of the subjects was conducted using the multiplex PCR-based invader assay. The prevalence of CKD was determined for stages 3-5 (defined as estimated glomerular filtration rate <60 ml/min/1.73 m2).
  
  
  RESULTS
  Logistic regression analysis revealed that SNPs APOA5 T - 1131C (rs662799), APOA5 T1259C (rs2266788), TOMM40 A/G (rs157580), and CETP TaqIB (rs708272) were significantly associated with CKD risk in those individuals genotyped, with age- and sex-adjusted odds ratios (ORs) per minor allele (and 95% confidence intervals (CIs)) of OR 1.22 (95% CI: 1.06-1.39), 1.19 (1.03-1.37), 1.27 (1.12-1.45), and 0.81 (0.71-0.92), respectively. Analysis of the gene-environment interaction revealed that body mass index (BMI) was a significant effect modifier for APOA5 T - 1131C (rs662799) and a marginally significant effect modifier for APOA5 T/C (rs2266788), with the interaction between BMI ≥30 and individuals with at least one minor allele of each genotype of OR 10.43 (95% CI: 1.29-84.19) and 3.36 (0.87-13.01), respectively.
  
  
  CONCLUSIONS
  Four polymorphisms in APOA5, TOMM40, and CETP were shown to be significantly associated with CKD risk, and a significant interaction between the two APOA5 SNPs and BMI on CKD risk was also demonstrated. This suggests the future possibility of personalized risk estimation for this life-limiting disease.
authors.affiliation: Department of Preventive Medicine, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan. a-hishi@med.nagoya-u.ac.jp.
authors.forename: Asahi
authors.initials: A
authors.lastname: Hishida
authors.forename: Kenji
authors.initials: K
authors.lastname: Wakai
authors.forename: Mariko
authors.initials: M
authors.lastname: Naito
authors.forename: Shino
authors.initials: S
authors.lastname: Suma
authors.forename: Tae
authors.initials: T
authors.lastname: Sasakabe
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Hamajima
authors.forename: Satoyo
authors.initials: S
authors.lastname: Hosono
authors.forename: Mikako
authors.initials: M
authors.lastname: Horita
authors.forename: Tanvir Chowdhury
authors.initials: TC
authors.lastname: Turin
authors.forename: Sadao
authors.initials: S
authors.lastname: Suzuki
authors.forename: Tara Sefanya
authors.initials: TS
authors.lastname: Kairupan
authors.forename: Haruo
authors.initials: H
authors.lastname: Mikami
authors.forename: Keizo
authors.initials: K
authors.lastname: Ohnaka
authors.forename: Isao
authors.initials: I
authors.lastname: Watanabe
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Uemura
authors.forename: Michiaki
authors.initials: M
authors.lastname: Kubo
authors.forename: Hideo
authors.initials: H
authors.lastname: Tanaka
mesh_terms: D000328:Adult; D000368:Aged; D000072040:Apolipoprotein A-V; D001054:Apolipoproteins A / Q000235:genetics*; D015992:Body Mass Index; D003430:Cross-Sectional Studies; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005919:Glomerular Filtration Rate; D006801:Humans; D007564:Japan; D015810:Linkage Disequilibrium; D050356:Lipid Metabolism / Q000235:genetics; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D051436:Renal Insufficiency, Chronic / Q000235:genetics* / Q000503:physiopathology; D012307:Risk Factors
chemical_list: C437704:APOA5 protein, human; D000072040:Apolipoprotein A-V; D001054:Apolipoproteins A