NPHS2 R229Q functional variant is associated with microalbuminuria in the general population (original) (raw)

We performed a case-control study to determine whether molecular variants of genes of the renin-angiotensin system were associated with the presence of albuminuria in non-insulin dependent diabetes mellitus (NIDDM). A total of 180 diabetic patients with persistent microalbuminuria [median urinary albumin (interquartile range) of 74 (54 to 126 mg/liter)] were matched with two control groups of diabetic patients without microalbuminuria [median urinary albumin 7 (5 to 10) mg/liter] for variables known to be associated with raised urinary albumin concentration including hemoglobin A1c and triglyceride. One control group was also matched for blood pressure and the other group was not, to allow assessment of interactions with hypertension. Association with the I/D polymorphism of the ACE gene and M235T variant of the angiotensinogen gene (AGT) with microalbuminuria and retinopathy was examined. There were no significant differences in genotype frequency between cases and controls for ACE or AGT irrespective of blood pressure matching. However, among subjects with microalbuminuria, those with the ACE DD genotype had a significantly greater urinary albumin excretion than individuals with a non-DD genotype [median 88 (68 to 170) mg/liter vs. 67 (53 to 113) mg/liter, P < 0.001]. More subjects with the DD than non-DD genotype had persistent albuminuria > 100 mg/liter, twice the upper normal range (60% vs. 38%, P = 0.006). When increased albumin excretion occurs, the presence of the ACE DD genotype appears to be associated with higher urinary albumin levels. No association with retinopathy was observed.

Aim: To evaluate whether microalbuminuria could be a marker of early tubular damage in individuals at risk of developing Balkan endemic nephropathy (BEN).Methods: A cross-sectional study was used to determine urinary albumin-to-creatinine ratio (UACR) in a test group of 61 participants from a BEN endemic region and control group of 64 participants from a nearby non-endemic region, both recruited from the general population of Bosnia and Herzegovina. The correlation between UACR and urinary b2 microglobulin-to-creatinine ratio (UBCR) and the receiver operating characteristic curve for UACR were analyzed in the test groups of 58 participants. The correlation analysis was also performed in a subset of nine subjects with elevated UBCR.Results: Medians, interquartile ranges and confidence intervals (CI) for medians of UACR in the test and control groups were 2 mg/mmol, 0.975–8.247 mg/mmol, 1.3472–3.2691 mg/mmol and 1 mg/mmol, 0.695–1.41 mg/mmol, 0.8466–1.2053 mg/mmol, respectively (P = 0.0001). Microalbuminuria was found in 30 of the 61 examinees in the test group, in contrast to six of the 64 examinees in the controls (P < 0.0001). Participants from the endemic region had 9.3 times the odds of having microalbuminuria in contrast to participants from the non-endemic region. Pearson's correlation coefficients r of the log-transformed ratios and Kendall–tau coefficients of rank correlation in the group of 58 and in a subset of nine subjects with elevated UBCR were: 0.55 (P < 0.0001); 0.317 (P = 0.0005) and 0.59 (P = 0.045); 0.48 (P = 0.037), respectively. The area under the curve for UACR was 0.882 (P = 0.0001), sensitivity 100% and specificity 67.3%.Conclusion: Microalbuminuria may be a useful marker of early tubular injury in individuals at risk of developing BEN.

The polymorphisms rs198358, rs5068 and rs632793 in the natriuretic peptide precursor A-B gene region [encoding atrial natriuretic peptides (ANP) and brain natriuretic peptides (BNP)] have been recently associated with ANP and BNP plasma concentrations and blood pressure (BP) in a large cohort study. We observed that GCG, the haplotype based on these polymorphisms and combining the three rare alleles associated with higher natriuretic peptides and lower BP in a recent report, was associated with BNP plasma levels and BP in a French study of 5212 middle-aged participants, Epidemiological Data on Insulin Resistance Syndrome study. With the 9-year follow-up of Epidemiological Data on Insulin Resistance Syndrome study, we were able to analyze the association of incident microalbuminuria (576 patients) and low estimated glomerular filtration rate (&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;60 ml/min; 246 incident patients) with the tested haplotypes. No haplotype, including GCG, the one combining the three rare alleles, was associated with incident patients of either microalbuminuria [odds ratio 1.27 (0.91-1.78), P = 0.15] or low estimated glomerular filtration rate [odds ratio 0.88 (0.54-1.46), P = 0.63]. This was consistent with a lack of effect on clinical renal outcomes found in previous studies and showed that even replicated and biologically plausible genetic association studies based on surrogate markers do not easily translate into clinically meaningful prognosis.