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.

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  • Author(s): Wang Y;Wang Y; Luk AO; Ma RC; So WY; Tam CH; Ng MC; Yang X; Lam V; Tong PC; Chan JC
  • Source:
    Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association [Nephrol Dial Transplant] 2012 Jan; Vol. 27 (1), pp. 190-6. Date of Electronic Publication: 2011 Jul 15.
  • Publication Type:
    Journal Article; Research Support, Non-U.S. Gov't
  • Language:
    English
  • Additional Information
    • Source:
      Publisher: Oxford University Press Country of Publication: England NLM ID: 8706402 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1460-2385 (Electronic) Linking ISSN: 09310509 NLM ISO Abbreviation: Nephrol Dial Transplant Subsets: MEDLINE
    • Publication Information:
      Publication: Oxford : Oxford University Press
      Original Publication: [Berlin ; New York, NY] : Springer International, [c1986-
    • Subject Terms:
      Biomarkers/*metabolism ; Cardiovascular Diseases/*genetics ; Diabetes Complications/*etiology ; Diabetes Mellitus, Type 2/*physiopathology ; Inflammation/*genetics ; Kidney Failure, Chronic/*etiology ; Polymorphism, Single Nucleotide/*genetics; Aged ; Asian People/genetics ; Cohort Studies ; Female ; Follow-Up Studies ; Glomerular Filtration Rate ; Humans ; Kidney Function Tests ; Male ; Middle Aged ; Prognosis ; Prospective Studies ; Risk Factors
    • 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.
    • Accession Number:
      0 (Biomarkers)
    • Publication Date:
      Date Created: 20110719 Date Completed: 20120529 Latest Revision: 20221207
    • Publication Date:
      20221213
    • Accession Number:
      10.1093/ndt/gfr343
    • Accession Number:
      21765051