AIMS/HYPOTHESIS: Identification of variants predicting development of renal dysfunction would offer substantial clinical benefits. There is evidence that coding non-synonymous variants in the gene encoding paraoxonase 2 (PON2) are associated with nephropathy in both type 1 and type 2 diabetes. METHODS: We examined the relationship between variation at the C311S and A148G polymorphisms (together with PON2 intronic variant rs12704795) and indices of renal dysfunction (progression to micro- and macroalbuminuria, plasma creatinine increases) in 3,374 newly diagnosed type 2 diabetic subjects from the UK Prospective Diabetes Study followed prospectively (median 14.0 years), using proportional hazards models, adjusted for sex, ethnicity and other known or putative risk factors. RESULTS: rs12704795 genotypes were associated with differing rates of development of microalbuminuria (relative risk [RR] for CC vs AA homozygotes 0.68 [95% CI 0.54-0.87], p=0.002) but not other measures of worsening renal function. Heterozygotes for C311S were more likely to develop microalbuminuria (RR=1.31 [95% CI 1.11-1.54], p=0.001) but less likely to double creatinine levels during follow-up (RR=0.49 [95% CI 0.27-0.89], p=0.02). There was no corroboration of this latter association for related outcomes and no prior evidence supports heterosis effects at this locus. CONCLUSIONS/ INTERPRETATION: We conclude that the PON2 variants typed in this study have, at best, a small effect on the risk of renal dysfunction in type 2 diabetes.
AIMS/HYPOTHESIS: Identification of variants predicting development of renal dysfunction would offer substantial clinical benefits. There is evidence that coding non-synonymous variants in the gene encoding paraoxonase 2 (PON2) are associated with nephropathy in both type 1 and type 2 diabetes. METHODS: We examined the relationship between variation at the C311S and A148G polymorphisms (together with PON2 intronic variant rs12704795) and indices of renal dysfunction (progression to micro- and macroalbuminuria, plasma creatinine increases) in 3,374 newly diagnosed type 2 diabetic subjects from the UK Prospective Diabetes Study followed prospectively (median 14.0 years), using proportional hazards models, adjusted for sex, ethnicity and other known or putative risk factors. RESULTS:rs12704795 genotypes were associated with differing rates of development of microalbuminuria (relative risk [RR] for CC vs AA homozygotes 0.68 [95% CI 0.54-0.87], p=0.002) but not other measures of worsening renal function. Heterozygotes for C311S were more likely to develop microalbuminuria (RR=1.31 [95% CI 1.11-1.54], p=0.001) but less likely to double creatinine levels during follow-up (RR=0.49 [95% CI 0.27-0.89], p=0.02). There was no corroboration of this latter association for related outcomes and no prior evidence supports heterosis effects at this locus. CONCLUSIONS/ INTERPRETATION: We conclude that the PON2 variants typed in this study have, at best, a small effect on the risk of renal dysfunction in type 2 diabetes.
Authors: John P A Ioannidis; Thomas A Trikalinos; Evangelia E Ntzani; Despina G Contopoulos-Ioannidis Journal: Lancet Date: 2003-02-15 Impact factor: 79.321
Authors: I Kockum; A Lernmark; G Dahlquist; A Falorni; W A Hagopian; M Landin-Olsson; L C Li; H Luthman; J P Palmer; C B Sanjeevi; G Sundkvist; I J Ostman Journal: Horm Metab Res Date: 1996-07 Impact factor: 2.936
Authors: Sudeshna Dasgupta; F Yesim Demirci; Amy S Dressen; Amy H Kao; Elisa Y Rhew; Rosalind Ramsey-Goldman; Susan Manzi; Candace M Kammerer; M Ilyas Kamboh Journal: BMC Med Genet Date: 2011-01-11 Impact factor: 2.103
Authors: Amy K Mottl; Suma Vupputuri; Shelley A Cole; Laura Almasy; Harald H H Göring; Vincent P Diego; Sandra Laston; Nawar Shara; Elisa T Lee; Lyle G Best; Richard R Fabsitz; Jean W MacCluer; Jason G Umans; Kari E North Journal: J Am Soc Nephrol Date: 2009-04-15 Impact factor: 10.121
Authors: Farook Thameem; Xin He; V Saroja Voruganti; Subrata D Nath; Paolo Fanti; John Blangero; Jean W Maccluer; Anthony G Comuzzie; Nedal H Arar; Hanna E Abboud Journal: Kidney Blood Press Res Date: 2009-06-18 Impact factor: 2.687
Authors: Philip W Connelly; Bernard Zinman; Graham F Maguire; Mary Mamakeesick; Stewart B Harris; Robert A Hegele; Ravi Retnakaran; Anthony J G Hanley Journal: J Lipid Res Date: 2009-01-18 Impact factor: 5.922