Paraoxonase 2 (PON2) polymorphisms and development of renal dysfunction in type 2 diabetes: UKPDS 76.
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. METHO...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Journal article |
| Language: | English |
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2006
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| _version_ | 1826288143517614080 |
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| author | Calle, R McCarthy, M Banerjee, P Zeggini, E Cull, C Thorne, K Wiltshire, S Terra, S Meyer, D Richmond, J Mancuso, J Milos, P Fryburg, D Holman, R |
| author_facet | Calle, R McCarthy, M Banerjee, P Zeggini, E Cull, C Thorne, K Wiltshire, S Terra, S Meyer, D Richmond, J Mancuso, J Milos, P Fryburg, D Holman, R |
| author_sort | Calle, R |
| collection | OXFORD |
| description | 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. |
| first_indexed | 2024-03-07T02:09:16Z |
| format | Journal article |
| id | oxford-uuid:a00c1393-c216-44c2-8d39-b89988b15cd6 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T02:09:16Z |
| publishDate | 2006 |
| record_format | dspace |
| spelling | oxford-uuid:a00c1393-c216-44c2-8d39-b89988b15cd62022-03-27T02:02:36ZParaoxonase 2 (PON2) polymorphisms and development of renal dysfunction in type 2 diabetes: UKPDS 76.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:a00c1393-c216-44c2-8d39-b89988b15cd6EnglishSymplectic Elements at Oxford2006Calle, RMcCarthy, MBanerjee, PZeggini, ECull, CThorne, KWiltshire, STerra, SMeyer, DRichmond, JMancuso, JMilos, PFryburg, DHolman, RAIMS/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. |
| spellingShingle | Calle, R McCarthy, M Banerjee, P Zeggini, E Cull, C Thorne, K Wiltshire, S Terra, S Meyer, D Richmond, J Mancuso, J Milos, P Fryburg, D Holman, R Paraoxonase 2 (PON2) polymorphisms and development of renal dysfunction in type 2 diabetes: UKPDS 76. |
| title | Paraoxonase 2 (PON2) polymorphisms and development of renal dysfunction in type 2 diabetes: UKPDS 76. |
| title_full | Paraoxonase 2 (PON2) polymorphisms and development of renal dysfunction in type 2 diabetes: UKPDS 76. |
| title_fullStr | Paraoxonase 2 (PON2) polymorphisms and development of renal dysfunction in type 2 diabetes: UKPDS 76. |
| title_full_unstemmed | Paraoxonase 2 (PON2) polymorphisms and development of renal dysfunction in type 2 diabetes: UKPDS 76. |
| title_short | Paraoxonase 2 (PON2) polymorphisms and development of renal dysfunction in type 2 diabetes: UKPDS 76. |
| title_sort | paraoxonase 2 pon2 polymorphisms and development of renal dysfunction in type 2 diabetes ukpds 76 |
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