title: Predictive role of multilocus genetic polymorphisms in cardiovascular disease and inflammation-related genes on chronic kidney disease in Type 2 diabetes--an 8-year prospective cohort analysis of 1163 patients.
abstract: BACKGROUND
  Chinese diabetic patients are at greater risk of developing chronic kidney disease (CKD) than Caucasian counterparts. In this hypothesis-generating study, we examined the independent and joint effects of multiple genetic variants on CKD in a prospective Chinese cohort of Type 2 diabetic patients.
  
  
  METHODS
  Seventy-seven single-nucleotide polymorphisms (SNPs) of 54 candidate genes for cardiorenal diseases and inflammation were genotyped in 1163 patients with no past history of CKD at baseline. CKD was defined as the first estimated glomerular filtration rate <60 mL/min/1.73 m(2) or the first hospitalization with a diagnosis of renal disease.
  
  
  RESULTS
  In Cox-regression analysis, 15 SNPs of 13 genes were associated with incident CKD. After correction for multiple comparisons, 6 SNPs including PON1 55Met, PON2 311Cys CETP-629C, ITGA2 873A, LTA 26Asn and LTA 252Gly remained independently associated with CKD, with respective hazard ratios (95% confidence interval):2.6 (1.4-4.8, P = 0.002), 1.5 (1.2-1.9, P = 0.003), 1.4 (1.1-1.7, P = 0.001), 2.2 (1.3-3.7, P = 0.002), 1.6 (1.1-2.2, P = 0.008) and 1.5 (1.1-2.1, P = 0.019). Analysis of joint effect of the six SNPs showed stepwise increase in risk of CKD with the accumulation of risk alleles and weighted genetic risk score (P(trend) = 8.9 × 10(-7) and 4.0 × 10(-5), respectively).
  
  
  CONCLUSIONS
  In Type 2 diabetes, there are independent and joint effects of multiple genetic variants on risk of CKD. Risk associations with PON1, PON2, CETP, ITGA2 and LTA genetic polymorphisms underline the importance of lipid metabolism, haemostasis and inflammation in the development of CKD in patients with Type 2 diabetes.
authors.affiliation: Department of Medicine and Therapeutics, The Chinese University of Hong Kong, The Prince of Wales Hospital, Shatin, Hong Kong SAR, China. yingwang@cuhk.edu.hk
authors.forename: Ying
authors.initials: Y
authors.lastname: Wang
authors.forename: Andrea O Y
authors.initials: AO
authors.lastname: Luk
authors.forename: Ronald C W
authors.initials: RC
authors.lastname: Ma
authors.forename: Wing-Yee
authors.initials: WY
authors.lastname: So
authors.forename: Claudia H T
authors.initials: CH
authors.lastname: Tam
authors.forename: Maggie C Y
authors.initials: MC
authors.lastname: Ng
authors.forename: Xilin
authors.initials: X
authors.lastname: Yang
authors.forename: Vincent
authors.initials: V
authors.lastname: Lam
authors.forename: Peter C Y
authors.initials: PC
authors.lastname: Tong
authors.forename: Juliana C N
authors.initials: JC
authors.lastname: Chan
mesh_terms: D000368:Aged; D044466:Asian People / Q000235:genetics; D015415:Biomarkers / Q000378:metabolism*; D002318:Cardiovascular Diseases / Q000235:genetics*; D015331:Cohort Studies; D048909:Diabetes Complications / Q000209:etiology*; D003924:Diabetes Mellitus, Type 2 / Q000503:physiopathology*; D005260:Female; D005500:Follow-Up Studies; D005919:Glomerular Filtration Rate; D006801:Humans; D007249:Inflammation / Q000235:genetics*; D007676:Kidney Failure, Chronic / Q000209:etiology*; D007677:Kidney Function Tests; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011379:Prognosis; D011446:Prospective Studies; D012307:Risk Factors
chemical_list: D015415:Biomarkers