Association of TRPV5 gene polymorphism with calcium urolithiasis: a case-control study from West Bengal, India.

PURPOSE: Present study was intended to investigate the potential contribution of TRPV5 gene polymorphisms with calcium urolithiasis in the population of West Bengal, India. METHODS: A case-control study was performed with 152 calcium urolithiasis patients and 144 corresponding healthy controls. Epidemiological and clinical parameters were documented as well as peripheral blood sample was collected from each individual, followed by genomic DNA isolation. Then to identify genetic variants of TRPV5, the entire coding region and exon-intron boundaries of the gene were amplified by polymerase chain reaction using specific oligonucleotide primers and then genotypes were determined by bi-directional DNA sequencing and sequence alignment between case and control individuals. RESULTS: Urinary calcium excretion was found to be significantly high (p value < 0.0001) in urolithiasis patients as compared to controls. A total of 14 SNPs were obtained of which one non-synonymous (rs4236480; p.Arg154His; CGT > CAT), one synonymous (rs4252417; p.Tyr278Tyr; TAC > TAT) and three intronic (rs4252400, rs4252402, rs4236481) SNPs were found to be significantly associated with increased risk of urolithiasis. For non-synonymous SNP rs4236480, 'A' was found to be the risk allele (OR 1.77, 95% CI 1.24-2.51; p value 0.001) and genotype frequency analysis revealed that individuals carrying variant genotype AA were more prone to the disease than individuals with wild genotype GG (OR 3.09, 95% CI 1.26-7.59; p value 0.0136), indicating AA as the risk genotype. CONCLUSIONS: The non-synonymous SNP rs4236480 showed significant association with urolithiasis risk in West Bengal population of India. Future translational and larger population-based studies are required to validate our finding.

Physiological and behavioural responses to acid and osmotic stress and effects of Mucuna extract in Guppies.

Variation in pH (acidification) and salinity conditions have severe impact at different levels of biological organization in fish. Present study focused to assess the effects of acidification and salinity changes on physiological stress responses at three different levels of function: i) hormonal and oxidative response, ii) osmoregulation and iii) reproduction, in order to identify relevant biomarkers. Second objective of the study was to evaluate the efficacy of plant (Mucuna pruriens) extract for alleviating pH and salinity related stress. Guppies (Poecilia reticulata) were exposed to different pH (6.0, 5.5, 5.0) and salinity (1.5, 3.0, 4.5 ppt) for 7, 14 and 21 days. Following exposure to stress for respective duration, fish were fed diet containing methanol extract of Mucuna seeds (dose 0.80 gm/kg feed) for 7, 14 and 21 days to measure their possible recovery response. Stress hormone (cortisol), hepatic oxidative stress parameters [superoxide dismutase (SOD), catalase (CAT), glutathione reductase (GRd), glutathione peroxidise (GPx), glutathione S-transferase (GST), malondialdehyde (MDA), glutathione (GSH)], gill osmoregulatory response (Na+-K+ATPase activity), sex steroid profiles and mating behaviours (gonopodial thrust and gestation period) were estimated. Cortisol and MDA levels increased with dose and duration of acid and salinity stress, and cortisol levels were higher in males than in females. Effect on Na+-K+ATPase activity was more intense by salinity stress rather than pH induced stress. Both acid and salinity stress reduced sex steroid levels, and mating response was highly affected by both stresses in a dose- and duration-dependent manner. Mucuna treatment reduced stress-induced alteration of cortisol, MDA, Na+-K+ATPase activity and reproductive parameters. Dietary administration of Mucuna seed extract decreased the intensity of environmental stressors at all three functional levels. Mucuna treatment was more effective against salinity stress than acid stress. Thus, cortisol, oxidative stress marker MDA and Na+-K+ATPase could be effective indicators for acid and salinity stress in wild and domestic fish populations. Dietary administration of Mucuna extract may limit the detrimental effects of acidification and salinity variations that are the inevitable outcomes expected under global climate change conditions.

Genetic Alterations in Pendrin (SLC26A4) Gene in Adult Hypothyroid Patients.

Current study was aimed to screen the SLC26A4 gene in 127 nonautoimmune and noncongenital hypothyroid patients, who were under optimal iodine nutrition and devoid of any characteristics of Pendred syndrome from eastern part of Indian population. 8 single nucleotide variants/mutations were identified in heterozygous state in 20% patient population, which include 1 novel nonsynonymous (p.C18S), 1 novel intronic (g.942C>A), 3 known nonsynonymous (p.S23X, p.V239D, and p.I455F), and 3 known intronic (g.23034G>T, g.29641C>G, and g.33893T>C) variants. Only g.23034G>T was noted also in homozygous state in 2% patient population. However, Controls exhibited only the variations g.23034G>T and p.I455F. Therefore, present study reports for the first time that the observed novel variants in pendrin gene might be linked with autoimmune negative hypothyroidism, without any characteristics of Pendred syndrome and/or congenital hypothyroidism. While, all observed known variants/mutations were reported with either Pendred syndrome and/or congenital hypothyroidism earlier, but never with nonautoimmune adult hypothyroidism solely. Thereby, the absence of any features of Pendred syndrome and/or congenital hypothyroidism in patients with observed known nonsynonymous variants/mutations may be due to either heterozygous state of each variant or differential domain specific activity of ions trafficking in the respective organ. The analysis of amino acid change at least for p.C18S, p.S23X, and p.V239D in correlation with phenotypic characteristics of respective patients might assume a possible effect on protein structure and function. Altogether, we report for the first time that genetical variations in SLC26A4 gene could play an important role in development of nonautoimmune adult hypothyroidism.

The Demographic Diversity of Food Intake and Prevalence of Kidney Stone Diseases in the Indian Continent.

Food intake plays a pivotal role in human growth, constituting 45% of the global economy and wellbeing in general. The consumption of a balanced diet is essential for overall good health, and a lack of equilibrium can lead to malnutrition, prenatal death, obesity, osteoporosis and bone fractures, coronary heart diseases (CHD), idiopathic hypercalciuria, diabetes, and many other conditions. CHD, osteoporosis, malnutrition, and obesity are extensively discussed in the literature, although there are fragmented findings in the realm of kidney stone diseases (KSD) and their correlation with food intake. KSD associated with hematuria and renal failure poses an increasing threat to healthcare infrastructures and the global economy, and its emergence in the Indian population is being linked to multi-factorial urological disorder resulting from several factors. In this realm, epidemiological, biochemical, and macroeconomic situations have been the focus of research, even though food intake is also of paramount importance. Hence, in this article, we review the corollary associations with the consumption of diverse foods and the role that these play in KSD in an Indian context.

Does quality of drinking water matter in kidney stone disease: A study in West Bengal, India.

Purpose: The combined interaction of epidemiology, environmental exposure, dietary habits, and genetic factors causes kidney stone disease (KSD), a common public health problem worldwide. Because a high water intake (>3 L daily) is widely recommended by physicians to prevent KSD, the present study evaluated whether the quantity of water that people consume daily is associated with KSD and whether the quality of drinking water has any effect on disease prevalence. Materials and Methods: Information regarding residential address, daily volume of water consumption, and source of drinking water was collected from 1,266 patients with kidney stones in West Bengal, India. Drinking water was collected by use of proper methods from case (high stone prevalence) and control (zero stone prevalence) areas thrice yearly. Water samples were analyzed for pH, alkalinity, hardness, total dissolved solutes, electrical conductivity, and salinity. Average values of the studied parameters were compared to determine if there were any statistically significant differences between the case and control areas. Results: We observed that as many as 53.6% of the patients consumed <3 L of water daily. Analysis of drinking water samples from case and control areas, however, did not show any statistically significant alterations in the studied parameters. All water samples were found to be suitable for consumption. Conclusions: It is not the quality of water, rather the quantity of water consumed that matters most in the occurrence of KSD.

Polymorphisms of PTH (Parathyroid Hormone) Gene and Risk of Kidney Stone Disease: A Case-Control Study from West Bengal, India.

OBJECTIVE: To investigate the potential contribution of parathyroid hormone (PTH) gene polymorphisms in kidney stone disease (KSD), a global clinical problem impacting major burden on public health care system worldwide. METHODS: A case-control study was performed in West Bengal (India) with 152 patients reported with calcium-rich stone in kidney and 144 corresponding normal healthy individuals as controls. To identify genetic variants of PTH, the entire coding region, exon-intron boundaries and a few hundred nucleotides downstream the exon 3 (3' UTR region) was bi-directionally sequenced for all the study participants. RESULTS: Two intronic (rs694 and rs6254) and one synonymous (rs6256, located in exon 3) variant were identified along with 2 single nucleotide polymorphisms (SNPs) (rs307247 and rs307248) in the 3' UTR of the PTH gene. Allele and genotype frequency analysis of these SNPs revealed that rs6254 and rs6256 had moderate association with increased risk of KSD. The 2 SNPs (rs307247 and rs307248) of the 3' UTR, which were in strong linkage disequilibrium, were found to be significantly associated with kidney stone risk in the population of West Bengal, India. CONCLUSION: This is the first time report in the world, regarding association of PTH gene polymorphisms with KSD. Our finding suggests that PTH gene polymorphisms can be used as potential genetic markers for early detection of KSD and for preventing its occurrence. Additional studies with larger sample size are essential to validate our result.

Association of calcitonin receptor gene (CALCR) polymorphism with kidney stone disease in the population of West Bengal, India.

Kidney Stone Disease (KSD) is a complex urologic disorder with strong genetic constituent. Earlier association studies have indicated that the genetic polymorphisms are the potential cause of stone materialization; however unfortunately, the actual genetic signature is still unknown. Therefore, present study was aimed to investigate the potential contribution of two important polymorphisms of calcitonin receptor gene (CALCR): (i) rs1801197 (Leu447Pro) and (ii) rs1042138 (3'UTR+18C>T) in renal stone formation. Accordingly, we enrolled 152 patients registered with calcium-rich stone in kidney (case) and 144 corresponding age, sex and ethnicity matched healthy individuals (controls). Epidemiological and clinical data were recorded as well as peripheral blood sample was collected from each individual. Serum creatinine and urinary calcium level was found high in patients, compared to controls. Out of two studied polymorphisms, we have not found any significant association against the rs1042138 with KSD, nonetheless, significant high frequency (p=0.001; Odds ratio=1.81; 95% CI: 1.28-2.55) of risk allele T against the rs1801197 (T>C) in patient was noted. Moreover, significant association with KSD was noted by genotypic analysis of rs1801197 (Leu447Pro) in our population. Interestingly, male patients carrying TT genotype was found to be at high risk of stone formation, while no such association was observed in female patients. Altogether, present study indicated that the rs1042138 might not be used as a useful marker for susceptibility of kidney stone formation, whereas, the rs1801197 could definitely be considered as one of the risk factors for KSD in Indian population at least in West Bengal in particular.