Dataset Information

Comparative (1)H NMR metabolomic urinalysis of people diagnosed with Balkan endemic nephropathy, and healthy subjects, in Romania and Bulgaria: a pilot study.

ABSTRACT: (1)H NMR spectroscopy of urine has been applied to exploring metabolomic differences between people diagnosed with Balkan endemic nephropathy (BEN), and treated by haemodialysis, and those without overt renal disease in Romania and Bulgaria. Convenience sampling was made from patients receiving haemodialysis in hospital and healthy controls in their village. Principal component analysis clustered healthy controls from both countries together. Bulgarian BEN patients clustered separately from controls, though in the same space. However, Romanian BEN patients not only also clustered away from controls but also clustered separately from the BEN patients in Bulgaria. Notably, the urinary metabolomic data of two people sampled as Romanian controls clustered within the Romanian BEN group. One of these had been suspected of incipient symptoms of BEN at the time of selection as a 'healthy' control. This implies, at first sight, that metabolomic analysis can be predictive of impending morbidity before conventional criteria can diagnose BEN. Separate clustering of BEN patients from Romania and Bulgaria could indicate difference in aetiology of this particular silent renal atrophy in different geographic foci across the Balkans.

SUBMITTER: Mantle P

PROVIDER: S-EPMC3202861 | biostudies-literature | 2011 Jul

REPOSITORIES: biostudies-literature

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Comparative (1)H NMR metabolomic urinalysis of people diagnosed with Balkan endemic nephropathy, and healthy subjects, in Romania and Bulgaria: a pilot study.

Mantle Peter P Modalca Mirela M Nicholls Andrew A Tatu Calin C Tatu Diana D Toncheva Draga D

Toxins 20110704 7

(1)H NMR spectroscopy of urine has been applied to exploring metabolomic differences between people diagnosed with Balkan endemic nephropathy (BEN), and treated by haemodialysis, and those without overt renal disease in Romania and Bulgaria. Convenience sampling was made from patients receiving haemodialysis in hospital and healthy controls in their village. Principal component analysis clustered healthy controls from both countries together. Bulgarian BEN patients clustered separately from cont ...[more]

PMID: 22069742

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Project description:Balkan Endemic Nephropathy (BEN) is late-onset kidney disease thought to arise from chronic exposure to aristolochic acid, a phytotoxin that contaminates wheat supplies in rural areas of Eastern Europe. It has recently been demonstrated that humans are capable of perceiving aristolochic acid at concentrations below 40 nM as the result of high-affinity interactions with the TAS2R43 bitter taste receptor. Further, TAS2R43 harbors high-frequency loss-of-function mutations resulting in 50-fold variability in perception. This suggests that genetic variation in TAS2R43 might affect susceptibility to BEN, with individuals carrying functional forms of the receptor being protected by an ability to detect tainted foods.To determine whether genetic variation in TAS2R43 predicts BEN susceptibility, we examined genotype-phenotype associations in a case-control study. A cohort of 88 affected and 99 control subjects from western Bulgaria were genotyped with respect to two key missense variants and a polymorphic whole-gene deletion of TAS2R43 (W35S, H212R, and wt/?), which are known to affect taste sensitivity to aristolochic acid. Tests for association between haplotypes and BEN status were then performed.Three major TAS2R43 haplotypes observed in previous studies (TAS2R43-W35/H212, -S35/R212 and -?) were present at high frequencies (0.17, 0.36, and 0.47 respectively) in our sample, and a significant association between genotype and BEN status was present (P = 0.020; odds ratio 1.18). However, contrary to expectation, BEN was positively associated with TAS2R43-W35/H212, a highly responsive allele previously shown to confer elevated bitter sensitivity to aristolochic acid, which should drive aversion but might also affect absorption, altering toxin activation.Our findings are at strong odds with the prediction that carriers of functional alleles of TAS2R43 are protected from BEN by an ability to detect and avoid aristolochic acid exposure. Evidence for a positive association between high-sensitivity alleles and BEN status suggests instead that possession of toxin-responsive receptor variants may paradoxically increase vulnerability, possibly by shifting attractive responses associated with low-intensity bitter sensations. The broad-spectrum tuning of the ~25-member TAS2R family as a whole toward xenobiotics points to a potentially far-reaching relevance of bitter responses to exposure-related disease in both individuals and populations.

Dataset Information

Comparative (1)H NMR metabolomic urinalysis of people diagnosed with Balkan endemic nephropathy, and healthy subjects, in Romania and Bulgaria: a pilot study.

Publications

Comparative (1)H NMR metabolomic urinalysis of people diagnosed with Balkan endemic nephropathy, and healthy subjects, in Romania and Bulgaria: a pilot study.

Similar Datasets

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