Dataset Information

An IL-6 haplotype on human chromosome 7p21 confers risk for impaired renal function in type 2 diabetic patients.

ABSTRACT: The human chromosome 7p21 locus harbors a major gene that influences variation of glomerular filtration rate and development of end-stage renal disease. The pro-inflammatory IL-6 cytokine is a candidate gene since chronic inflammation has been implicated in diabetic nephropathy and this gene is located under the peak of linkage. To test this, single nucleotide polymorphism (SNP) and haplotype analyses were performed using a case-control study of 295 patients consisting of 138 with proteinuria, 157 with chronic renal failure and these were compared to 174 control patients with normal albumin excretion. Five tagging SNPs were selected for analysis based on linkage disequilibrium patterns and proximity to the functionally important -634G>C SNP in the IL-6 promoter. Initial analysis suggested that a -174G>C polymorphism may be associated with risk of chronic renal failure but this was not significant after Bonferroni correction. While haplotype analyses showed no association with proteinuria; a significant association with chronic renal failure was found. There was significantly more of the GGGAGC haplotype among patients with chronic renal failure compared to controls and this association remained significant even after correction for multiple testing. Our study has found a specific IL-6 haplotype conferring risk for impaired renal function in patients with type 2 diabetes.

SUBMITTER: Ng DP

PROVIDER: S-EPMC2756185 | biostudies-literature | 2008 Aug

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

An IL-6 haplotype on human chromosome 7p21 confers risk for impaired renal function in type 2 diabetic patients.

Ng Daniel P K DP Nurbaya Siti S Ye Sandra H J SH Krolewski Andrzej S AS

Kidney international 20080521 4

The human chromosome 7p21 locus harbors a major gene that influences variation of glomerular filtration rate and development of end-stage renal disease. The pro-inflammatory IL-6 cytokine is a candidate gene since chronic inflammation has been implicated in diabetic nephropathy and this gene is located under the peak of linkage. To test this, single nucleotide polymorphism (SNP) and haplotype analyses were performed using a case-control study of 295 patients consisting of 138 with proteinuria, 1 ...[more]

PMID: 18496509

Similar Datasets

Project description:Endothelial dysfunction is considered as a risk factor for cardiovascular disease, which is a consistent finding in diabetic mellitus type 2 (DMT2). First-degree relatives of DMT2 patients have a higher risk of developing DMT2 later on the life. We aimed to investigate whether impaired endothelial function exists in siblings of DMT2 patients.As endothelial function markers, plasma E-selectin, soluble inter-cellular adhesion molecule-1 (sICAM-1), and endothelin-1 (ET-1) were measured on 27 DMT2 patients (9 m/18f; mean age: 48.48 ± 6.75 years), 28 siblings of DMT2 patients (14 m/14f; mean age: 44.54 ± 7.10 years), and 30 control subjects (18 m/12f; mean age: 44.72± 7.56 years) without any family history of diabetes. All the groups were matched by gender, age, and body mass index (BMI).Plasma levels of ET-1, sICAM-1, and E-selectin were significantly higher in the DMT2 group compared to the control group (ET-1:0.79 ± 1.63 pg/ml vs. 0.33 ± 0.08 pg/ml; PCD = 0.049, sICAM-1: 71.15 ± 27.20 ng/ml vs. 34.57 ± 22.56 ng/ml; PCD = 0.001, E-selectin: 22.45 ± 11.57 ng/ml vs. 16.28 ± 7.50 ng/ml; PCD =0.026). There was a significant difference in sICAM-1 levels between siblings (62.08 ± 26.37 ng/ml) and controls (PCS = 0.002), but not between siblings and DMT2 patients (PSD = 0.411). Moreover, a significant difference was observed in ET-1 levels between siblings (0.75 ± 1.26 pg/ml) and controls (PCS = 0.031), but not between siblings and DMT2 patients (PSD = 0.751). There was also a significant difference in E-selectin levels between DMT2 patients and siblings (16.56 ± 8.71 ng/ml; PSD =0.028); however, the difference in E-selectin levels was not statistically significant between siblings and controls (PCS = 0.919).Endothelial function markers in the siblings of DMT2 patients are increased in comparision to the control group Therefore; family history in the DMT2 patients seems to be a risk factor for endothelial function. Furthermore, endothelial dysfunction is available very early in the DMT2 patients, even before overt hyperglycemia ensues (in siblings), and may play a key role in the etiopathology of the vasculopathy associated with DMT2.

Project description:BACKGROUND:Albuminuria is the early manifestation of the pathogenesis of diabetic nephropathy (DN). The current study was to investigate the relationship of pulmonary function with albuminuria in type 2 diabetic patients with preserved renal function to evaluate the role of pulmonary function in the early stage of DN. METHODS:A total of 326 patients with type 2 diabetes mellitus (T2DM) including 270 without albuminuria and 56 with albuminuria, and 265 non-diabetic patients were enrolled. The patients' general information, and the parameters of pulmonary function, including forced vital capacity (FVC), forced expiratory volume in 1?s (FEV1), FEV1/FVC, total lung capacity (TLC), diffusion capacity for carbon monoxide of lung (DLCO) were compared between T2DM and control groups, as well as T2DM patients with and without albuminuria groups. All pulmonary function parameters were expressed as a percentage of those predicted (%pred). Logistic regression models were constructed to test the association of albuminuria and pulmonary function. RESULTS:The values of FVC%pred, FEV1%pred, TLC%pred and DLCO%pred were lower, and the proportion of subjects with FVC%pred <?80, FEV1%pred <?80, and DLCOc%pred <?80 was higher in T2DM subjects than controls (all P?<?0.05). Subgroup analysis of diabetic patients showed that the values of FVC%pred, FEV1%pred, TLC%pred, and DLCOc%pred (97.18?±?13.45, 93.95?±?14.51, 90.64?±?9.97, 87.27?±?13.13, respectively) were significantly lower in T2DM subjects with albuminuria than those without albuminuria (103.94?±?14.12, 99.20?±?14.25, 93.79?±?10.36, 92.62?±?13.45, all P?<?0.05). There was a significantly negative correlation between the urine albumin-to-creatinine ratio (UACR) and DLCOc%pred (r =?-?0.143, P =?0.010) in spearman linear correlation test. In logistic regression analysis, the FVC%pred (OR 0.965, 95%CI 0.944-0.988), FEV1%pred (OR 0.975, 95%CI 0.954-0.996), and DLCOc%pred (OR 0.974, 95%CI 0.951-0.998) were independently associated with albuminuria after adjustments for smoking index, duration, HbA1c, FBG, and TG. CONCLUSION:Our results demonstrated albuminuria is associated with a restrictive pulmonary function as well as pulmonary diffusion function in T2DM with preserved renal function, which remind us to be alert of the pulmonary function decline even in the early stage of DN.

Project description:BackgroundInfection with, and treatment of HIV is associated with effects on glycaemia and renal function. The purpose of this study was therefore to compare glycaemic control and albuminuria in HIV-positive and HIV-negative type 2 diabetic patients.Materials and methodsDiabetic patients with and without HIV infection were recruited from a diabetic clinic at Chris Hani Baragwanath Hospital in Soweto, South Africa. Data was collected on weight, height, HbA1c, fasting glucose, urine albumin:creatinine ratio, HIV status, CD4 counts, viral load and concomitant therapies. Multivariable regression analysis was used to isolate the determinants of fasting glucose and HbA1c levels and risk factors for albuminuria.ResultsData were collected from 106 HIV-positive and 214 HIV-negative diabetics. All HIV infected subjects were receiving anti-retroviral therapy. The determinants of fasting glucose levels (log) were HIV infection (β = 0.04, p = 0.01) and use of anti-hypertensive agents (β = 0.07, p = 0.0006), whilst for HbA1c levels (log) they were HIV infection (β = -0.03, p = 0.03), BMI (β = 0.004, p = 0.0005), statin use (β = 0.04, p = 0.002) and glucose levels (β = 0.01, p<0.0005). In HIV-positive subjects, CD4 counts were negatively associated with glucose levels (β = -0.0002, p = 0.03). The risk factors for albuminuria were (odds ratio [95% CIs]) dyslipidaemia (1.94 [1.09, 3.44], p = 0.02) and HbA1c levels (1.24 [1.12, 1.38], p<0.0001).DiscussionThese data suggest that glycaemic control is worse in type 2 diabetic subjects with HIV infection and that HbA1c underestimates glycaemia in these patients. Albuminuria was not associated with HIV-positivity. The negative relationship of CD4 counts with glucose levels may reflect viral removal and easing of the associated inflammatory response. It is possible that the association of statin and anti-hypertensive therapies with high HbA1c and glucose levels, respectively, is due to such therapies being given largely to subjects with poor glycaemic control.

Dataset Information

An IL-6 haplotype on human chromosome 7p21 confers risk for impaired renal function in type 2 diabetic patients.

Publications

An IL-6 haplotype on human chromosome 7p21 confers risk for impaired renal function in type 2 diabetic patients.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets