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        "titulo" => "The E23K polymorphism of the KCNJ11gene is associated with lower insulin release in patients with Autosomal Dominant Polycystic Kidney Disease"
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    "textoCompleto" => "<p class="elsevierStylePara"><span class="elsevierStyleBold">Dear Editor&#44;</span></p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara">Results of large-scale studies and meta-analyses<span class="elsevierStyleSup">1-4</span> strongly indicate that K23 allele is associated with higher prevalence and incidence of type 2 diabetes in adult Caucasians&#46; Some studies<span class="elsevierStyleSup">1&#44;5</span> have shown that the K allele may have a diabetogenic effect by impairing glucose-induced insulin release&#46;</p><p class="elsevierStylePara">The aim of our study was to investigate an association between E23K <span class="elsevierStyleItalic">KCNJ11 </span>gene polymorphism with anthropometric&#44; biochemical&#44; b-cell secretion and insulin sensitivity parameters among adult ADPKD patients with normal kidney function and no diagnosis of diabetes&#46; The comparison of genotype-phenotype associations between ADPKD and non-ADPKD subjects could reveal a hypothetical mechanism of genetic determination of diabetes specific for ADPKD patients&#46;</p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara"><span class="elsevierStyleBold">METHODS</span></p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara">The study group included 49 adult individuals with diagnosed ADPKD &#40;19 males&#44; 30 females&#41; while the control group comprised 50 gender- and age-matched healthy individuals &#40;22 males&#44; 28 females&#41;&#46;</p><p class="elsevierStylePara">The oral glucose tolerance test &#40;OGTT&#41; was performed according to WHO guidelines &#40;with 75 g of glucose&#41;&#46;<span class="elsevierStyleSup">6</span> Venous blood was collected to measure fasting glucose&#44; insulin&#44; total cholesterol&#44; LDL&#44; HDL and triglyceride levels&#46; Glucose concentration was measured by an enzymatic-amperometric method &#40;Super GL&#59; Dr M&#252;ller Ger&#228;tebau GmbH&#44; Freital&#44; Germany&#41;&#46; Insulin concentration was measured by microparticle enzyme immunoassay &#40;AxSYM MEIA&#59; Abbott Laboratories&#44; Abbot Park&#44; USA&#46; For serum creatinine and lipid levels a Cobas Integra 800 bioanalyser was used&#46;</p><p class="elsevierStylePara">The beta-cell function indexes were used in our study&#59; ratios of insulin-to-glucose concentrations for each OGTT time point &#40;INS&#47;GLU 0&#44; 30&#44; 60&#44; 90&#44; 120&#41;&#44; ratio of the area under curve of insulin &#40;AUC Insulin&#41; and glucose &#40;AUC Glucose&#41; concentrations &#40;SECR AUC&#41;&#44; secretory 1<span class="elsevierStyleSup">st</span> phase &#40;SECR1P&#41; and 2<span class="elsevierStyleSup">nd</span> phase &#40;SECR2P&#41; calculated from the first 30 or 60 minutes of OGTT &#40;SECR1P 30 min&#44; SECR1P 60 min&#44; SECR2P 30 min&#44; SECR2P 60 min&#41;&#44; insulinogenic index &#40;INSGENIN&#41;&#44; and insulin sensitivity indexes&#58; insulin sensitivity composite index &#40;ISI COMP&#41;&#44; and Cederholm sensitivity index &#40;ISI CEDE&#41;&#46; The formulas of these indexes were presented in our previous study&#46;<span class="elsevierStyleSup">7</span></p><p class="elsevierStylePara">The genotypes of G67A &#40;E23K&#41; <span class="elsevierStyleItalic">KCNJ11 </span>polymorphism &#40;rs5219&#41; were determined using a by PCR-RFLP technique&#44; as described previously&#46;<span class="elsevierStyleSup">8</span></p><p class="elsevierStylePara">Mann-Whitney test was used for quantitative variables&#44; while the Fisher exact test was implemented for qualitative variables&#46;</p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara"><span class="elsevierStyleBold">RESULTS</span></p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara">Differences in E23K <span class="elsevierStyleItalic">KCNJ11 </span>genotype distribution among ADPKD patients &#40;33&#37; EE&#44; 51&#37; EK&#44; 16&#37; KK&#41; and controls &#40;46&#37; EE&#44; 42&#37; EK&#44; 12&#37; KK&#41; proved insignificant &#40;p&#61;&#46;39&#41;&#46; Both distributions were consistent with Hardy-Weinberg equilibrium &#40;p&#62;&#46;7&#41;&#46;</p><p class="elsevierStylePara"><span class="elsevierStyleBold">&#160;</span></p><p class="elsevierStylePara"><span class="elsevierStyleBold">ADPKD group</span></p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara">KK homozygotes were significantly younger than allele E carriers&#46; Other anthropometric parameters were not associated with genotype &#40;Table 1&#41;&#46;</p><p class="elsevierStylePara">There was a trend to lower serum total cholesterol concentration among KK homozygotes if compared to E allele carrriers&#44; but HDL-cholesterol was significantly lower among K allele carriers in comparison to EE homozygotes &#40;Table 1&#41;&#46; Glucose levels during OGTT did not differ significantly between the genotypes&#44; but we have found trend to lower insulin levels among K allele carriers than in EE homozygotes in the 30<span class="elsevierStyleSup">th</span> minute of OGTT &#40;Table 2&#41;&#46; Similarly&#44; in the 60<span class="elsevierStyleSup">th</span> minute of the test&#44; there was a trend to lower insulin levels among KK homozygotes than in E allele carriers&#46; INS&#47;GLU 30 min ratio and values of the SECR1P 30 min&#44; SECR2P 30 min and INSGENIN indexes were significantly lower among K allele carriers than in EE homozygotes&#46; No significant associations between <span class="elsevierStyleItalic">KCNJ11 </span>E23K genotype and other carbohydrate metabolism parameters were observed &#40;Table 2&#41;&#46;</p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara"><span class="elsevierStyleBold">Control group</span></p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara">Among KK homozygotes&#44; in comparison to E allele carriers&#44; significantly lower glucose levels in the 60<span class="elsevierStyleSup">th</span> minute of OGTT as well as lower insulin levels in the 60<span class="elsevierStyleSup">th</span> and 120<span class="elsevierStyleSup">th</span> minute of OGTT were observed &#8211; a similar trend was observed for insulin in the 90<span class="elsevierStyleSup">th</span> minute&#46; Moreover&#44; lower values of INS&#47;GLU 60 min and INS&#47;GLU 120 min ratios as well as area under curve &#40;AUC&#41; for insulin were observed among KK homozygous subjects&#46; A trend to lower SECR AUC and SECR2P 60 secretory indexes was found in KK homozygotes when compared to E allele carriers&#46; The remaining indexes of the pancreatic b-cell secretory function&#44; insulin sensitivity &#40;Table 2&#41;&#44; lipid metabolism and anthropometric parameters &#40;Table 1&#41; did not significantly differ between the genotype groups&#46;</p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara"><span class="elsevierStyleBold">DISCUSSION</span></p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara">Our report is the first evaluation of the association between E23K polymorphism of the <span class="elsevierStyleItalic">KCNJ11</span> gene and anthropometry&#44; lipid and glucose metabolism parameters in a homogenous group of patients with ADPKD&#46;</p><p class="elsevierStylePara">The results obtained in this study reveal an association between the <span class="elsevierStyleItalic">KCNJ11 </span>E23K variant and lower insulin secretion during OGTT among non-diabetic patients with ADPKD and non-ADPKD controls&#46; In patients with ADPKD such an influence was observed for carriers of one or two K alleles&#44; while among controls it was significant only among KK homozygotes&#46; Results of clinical studies on the E23K polymorphism indicated that among non-diabetic subjects<span class="elsevierStyleSup">9</span> IGT diagnosed individuals<span class="elsevierStyleSup">10</span> or patients with diabetes type 2<span class="elsevierStyleSup">11</span> the K23 variant is significantly associated with lower insulin secretion during OGTT&#46; Our study confirmed this association for ADPKD patients&#44; but it is possible that the model of genotype-phenotype association in ADPKD and non-ADPKD subjects is different &#40;eg&#46; dominant vs&#46; recessive&#41;&#46; Such results support the necessity for further study on the influence of this variant on the risk of pre- and post-transplant diabetes development among ADPKD patients&#46; It is possible that contrasting research results on the frequency of post-transplant diabetes in this group of patients will be clarified in the future by genetic studies&#46;</p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara"><span class="elsevierStyleBold">Conflicts of interest</span></p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara">The authors declare that they have no conflicts of interest related to the contents of this article&#46;</p><p class="elsevierStylePara"><a href="grande&#47;12111&#95;16025&#95;46176&#95;en&#95;t112111&#46;jpg" class="elsevierStyleCrossRefs"><img src="12111_16025_46176_en_t112111.jpg" alt="Association between the G67A &#40;rs5219 E23K&#41; variant of the KCNJ11 gene and anthropometric and biochemical parameters among ADPKD and control groups"></img></a></p><p class="elsevierStylePara">Table 1&#46; Association between the G67A &#40;rs5219 E23K&#41; variant of the KCNJ11 gene and anthropometric and biochemical parameters among ADPKD and control groups</p><p class="elsevierStylePara"><a href="grande&#47;12111&#95;16025&#95;46179&#95;en&#95;t2121112&#46;jpg" class="elsevierStyleCrossRefs"><img src="12111_16025_46179_en_t2121112.jpg" alt="Association between &#40;rs5219 E23K&#41; variant of the KCNJ11 gene and insulin sensitivity and pancreatic beta-cell secretory function parameters among ADPKD and control groups"></img></a></p><p class="elsevierStylePara">Table 2&#46; Association between &#40;rs5219 E23K&#41; variant of the KCNJ11 gene and insulin sensitivity and pancreatic beta-cell secretory function parameters among ADPKD and control groups</p>"
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