Relationship between genetic polymorphisms within the pro-oxidant/antioxidant systems and diabetic nephropathy - preliminary results
| Authors | |
|---|---|
| Year of publication | 2003 |
| Type | Article in Periodical |
| Magazine / Source | Diabetologia |
| MU Faculty or unit | |
| Citation | |
| Field | Endocrinology, diabetology, metabolism, nutrition |
| Keywords | diabetes; polymorphisms; antioxidant; diabetic nephropathy |
| Description | Background and Aims: Association of selected genetic polymorphisms in genes encoding for glyoxalase I (A111E GLYI), paraoxonase (R192Q and M55L PON), NAD(P)H: quinone oxidoreductase (P187S NQO1) and methylenetetrahydrofolate reductase (677C/T MTHFR) with diabetic nephropathy (DN) in patients with both type 1 and type 2 diabetes mellitus was studied. Further, interactions of studied polymorphisms with previously associated polymorphism 2184A/G in the gene for receptor of advanced glycation end products (2184A/G RAGE) were investigated. Materials and Methods: A total of 318 Caucasian subjects was so far enrolled in the association study: diabetics with parallel DN (n=135, mean age 63.7) and diabetics without DN (n=183, mean age 64.5). DN group comprised patients with (i) persistent proteinuria, (ii) chronic renal failure and (iii) end-stage renal disease (ESRD) with regular hemodialysis. Allele frequencies of polymorphisms were determined by polymerase chain reaction based methodology. Results: Significant difference in allele frequencies of the P187S NQO1 between DN and non-DN group was found; frequency of the P allele was higher in DN group (19.5% vs. 14.1%). Moreover, marginally significant association of allele T with DN was detected for the 677C/T MTHFR polymorphism (P=0.07); 36.7% in DN group vs. 32.1% in non-DN group. Nor PON Q192R neither M55L allele frequencies did not differed significantly, however, frequency of 192R was higher in DN than in non-DN group (28.9% vs. 25.7%). Frequencies of combined genotype combinations of MTHFR, NQO1 and PON polymorphisms were not significantly different between the DN and non-DN groups, however, proportion of a combination TT-SS-RR was apparently higher in the DN group. Similarly, frequencies of twofold genotype combinations of studied polymorphisms and 2184A/G RAGE did not differed significantly, which might indicate their independent asset to DN susceptibility. Conclusions: The preliminary data indicate that certain polymorphisms in genes encoding pro-oxidant/antioxidant enzymes could be regarded as contributors to genetic risk factors for DN. Association of these polymorphisms with susceptibility to develop DN and rate of progression and severity of DN is a subject of larger ongoing study. |
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