Significant association of MTHFD1 1958G>A single nucleotide polymorphism with nonsyndromic cleft lip and palate in Indian population

Objectives: Nonsyndromic cleft lip and palate (NSCLP) is genetically distinct from those with syndromic clefts, and accounts for ~70% of cases with Oral clefts. Folate, or vitamin B9, is an essential nutrient in our diet. Allelic variants in genes involved in the folate pathway might be expected to have an impact on risk of oral clefts. Given the key role of methylenetetrahydrofolate dehydrogenase 1 (MTHFD1) in folate metabolism, it would be of significant interest to assess its role in NSCLP etiology. Study Design: The present study aims at examining the association between MTHFD1 1958G>A polymorphism and NSCLP risk by conducting a case-control study in south Indian population. Our sample comprised of 142 cases with nonsyndromic clefts and 141 controls without clefts or family history of clefting. The MTHFD1 1958G>A polymorphism was genotyped using PCR-RFLP. Results: An increased risk was found for the heterozygous 1958GA (OR=2.44; P =0.020) and homozygous 1958AA (OR=2.45; P =0.012) genotypes in the children. When the dominant model (AG+AA vs GG) was applied the risk remained the same as co-dominant model, but the level of significance increased (OR=2.44; P =0.002). Conclusions: The results indicated the MTHFD1 1958G>A polymorphism to be one of the important genetic determinants of NSCLP risk in South Indian subjects

Perspectives on the relationship of renal disease and coronavirus disease 2019

Coronavirus disease 2019 (COVID-19) is now a pandemic and its death toll is rocketing up. Patients with acute kidney injury (AKI) and chronic kidney disease (CKD) are at high risk of developing COVID-19 complications and COVID-19 infection can also lead to renal dysfunction. Considering the importance of kidney function in COVID-19 patients, the present review is aimed to dig into the available evidence about kidney and COVID-19. We summarize the mechanisms underlying the renal injury in COVID-19 patients, and treatment strategies in dialysis and kidney transplant patients. We conclude, it is imperative to highlight the early monitoring of patients with AKI and carefully control kidney function during severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection

Genetic affinities among the lower castes and tribal groups of India: inference from Y chromosome and mitochondrial DNA

BACKGROUND: India is a country with enormous social and cultural diversity due to its positioning on the crossroads of many historic and pre-historic human migrations. The hierarchical caste system in the Hindu society dominates the social structure of the Indian populations. The origin of the caste system in India is a matter of debate with many linguists and anthropologists suggesting that it began with the arrival of Indo-European speakers from Central Asia about 3500 years ago. Previous genetic studies based on Indian populations failed to achieve a consensus in this regard. We analysed the Y-chromosome and mitochondrial DNA of three tribal populations of southern India, compared the results with available data from the Indian subcontinent and tried to reconstruct the evolutionary history of Indian caste and tribal populations. RESULTS: No significant difference was observed in the mitochondrial DNA between Indian tribal and caste populations, except for the presence of a higher frequency of west Eurasian-specific haplogroups in the higher castes, mostly in the north western part of India. On the other hand, the study of the Indian Y lineages revealed distinct distribution patterns among caste and tribal populations. The paternal lineages of Indian lower castes showed significantly closer affinity to the tribal populations than to the upper castes. The frequencies of deep-rooted Y haplogroups such as M89, M52, and M95 were higher in the lower castes and tribes, compared to the upper castes. CONCLUSION: The present study suggests that the vast majority (>98%) of the Indian maternal gene pool, consisting of Indio-European and Dravidian speakers, is genetically more or less uniform. Invasions after the late Pleistocene settlement might have been mostly male-mediated. However, Y-SNP data provides compelling genetic evidence for a tribal origin of the lower caste populations in the subcontinent. Lower caste groups might have originated with the hierarchical divisions that arose within the tribal groups with the spread of Neolithic agriculturalists, much earlier than the arrival of Aryan speakers. The Indo-Europeans established themselves as upper castes among this already developed caste-like class structure within the tribes

Strive for kidney health for everyone during COVID-19; the possible theme for the world kidney day 2021

Increasing awareness regarding CKD and self-care during COVID-19 pandemic has become the most important aspect for the nephrologists. Hence it is appropriate that the theme of the forthcoming World Kidney Day on 11 March 2021 should be “Strive for kidney health for everyone during COVID-19

Administration of metformin in type 2 diabetes mellitus patients with chronic kidney disease; facts and myths

There are few publications reporting adverse effects of metformin for patients with type 2 diabetes mellitus (T2DM) and chronic kidney disease (CKD). Although some of these reports have made big claims about the adverse effects of metformin in patients with renal failure, the majority of studies showed a superior safety profile for metformin compared with other antidiabetic medications in these patients. Further, metformin use is not contributing to an increased incidence of acute kidney injury (AKI). In conclusion, we suggest that a low dose of metformin is safe to use in patients with or without CKD. Multicenter randomized trials are required to further discover the benefits of the risk of metformin therapy in different stages of CKD and its effect on progression of CKD

Interleukin-10 gene promoter variants and susceptibility to diabetic nephropathy; a meta-analysis

Introduction: Diabetic nephropathy (DN) is a leading cause of chronic kidney disease (CKD) in diabetes patients. There is ample evidence that the inflammatory pathways are central to both diabetes and DN. Several studies that examined the link between the interleukin-10 (IL10) polymorphisms and DN risk yielded conflicting results. Objectives: The purpose of this meta-analysis is to evaluate the associations between IL10 promoter polymorphisms and DN risk. Methods: A bibliographic search was carried out on PubMed, Google scholar and Web of Science from the beginning until July 30, 2020. Association between IL10 promoter variants (-1082 A>G, -819 C>T and -592 C>A) and DN risk were assessed by considering diabetes without nephropathy (DWN) as well as healthy controls. Data were retrieved and the pooled odds ratio (OR) with 95% confidence interval (CI) was calculated. Results: For the IL10 -1082 A> G analysis, a total of 4 studies with DWN controls (682 cases and 529 controls) and 5 studies with healthy controls (1025 cases and 1625 controls) were considered. For the IL10 -819 C> T analysis, a total of three studies with DWN controls (9619 cases and 445 controls) and 5 studies with healthy controls (1005 cases and 1537 controls) were considered. For the IL10 -592 C> T analysis, a total of 5 studies with DWN controls (819 cases and 645 controls) and 5 studies with healthy controls (1005 cases and 1537 controls) were considered. In addition, there was no evidence of publication bias for IL10 promoter variants. No substantial association was observed between IL10 promoter variants and DN risk. Conclusion: Our study signifies that polymorphisms of IL10 -1082 A>G, -819 C>T and -592 C>A are not linked with DN risk

Lack of association between IRF6 polymorphisms and nonsyndromic oral clefts in South Indian population

Objective: This present study is aimed to investigate the association between interferon regulatory factor 6 (IRF6), single nucleotide polymorphisms (SNPs), and nonsyndromic cleft lip without without cleft palate (NSCLP) in the South Indian population. Subject and Methods: For this study, 190 unrelated NSCLP patients and 189 controls without clefts were genotyped with rs2235371 (V2741) and rs642961 SNPs using PCR-RFLP. The associations between NSCLP groups and IRF6 gene polymorphisms, as well as haplotypes, were analyzed using chi-squared test and 95% confidence interval (95%CI) of the odds ratios were calculated with the control groups as reference. Results: For controls, the minor allele frequencies of both variants, V2741 and rs642961, were 7.1% and 21.1%, respectively. Genotype data for both variants in control and cleft groups follow the Hardy Weinberg Equilibrium. Between cases with NSCLP and controls, the two SNPs showed no differences in frequencies of the genotypes or alleles. The pairwise linkage disequilibrium (LD) values (D’=1 and r2=0.027) between V2741 and rs642961 revealed that these two SNPs are not in strong LD. Haplotype G-T showed a significantly reduced risk for oral clefts (p<0.001) and haplotype A-T increased the risk for oral clefts (p=0.043). Gene-gene interaction showed that the higher risk group contains more GG-CC combination of cases that the controls, but this model was not significantly associated with cleft status (p=0.136) Conclusion: In conclusion, while IRF6 is strongly associated in other populations, this study demonstrated that variants in IRF6 may play a role in NSCLP in a South Indian population, but other genes are expected to play a role in this population as well

Genetic association of ACE gene I/D polymorphism with the risk of diabetic kidney disease; a meta-analysis

Introduction: Diabetic nephropathy (DN) is a progressive renal disease characterized by persistent albuminuria that leads to end-stage renal disease in both type 1 diabetes (T1DM) and type 2 diabetes (T2DM) patients. The renin-angiotensin-aldosterone system (RAAS) plays a major role in the onset and progression of DN. Objectives: The present meta-analysis is intended to synthesize evidence on the association between ACE gene insertion and deletion (ACE I/D) polymorphism and the risk of DN. Methods: PubMed, Scopus, Google Scholar and Embase were searched to retrieve relevant publications. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to evaluate the association between ACE I/D polymorphism and DN risk. The Cochrane Q test and I2 statistic were used to detect heterogeneity. To assess between-study heterogeneity, subgroup analysis and sensitivity analysis were performed. Funnel plots and Egger’s test were used to estimate publication bias. Results: Around 45 articles (47 studies) with 6124 patients of DN and 2492 T2DM patients (controls) were ultimately considered for meta-analysis. Overall, the ACE I/D polymorphism was associated with DN under three different genetic models (allelic model: OR = 1.34; 95% CI: 1.20- 1.49; P 50%) was present in the analysis for all ethnic groups. Further, there is no evidence for publication bias in this meta-analysis. Conclusion: The current meta-analysis provided confirmation that the ACE I/D polymorphism is correlated with an increased risk of DN in patients with T2DM and the D allele of ACE I/D was a susceptible factor

Herbal antioxidants and renal ischemic-reperfusion injury; an updated review

Renal ischemia-reperfusion (RIR) is a pathological condition due to transient restriction of blood flow to the kidneys, which is followed by the subsequent recovery of perfusion and re-oxygenation. RIR injury contributes to the progression of renal dysfunction including acute kidney injury (AKI) in native and renal allograft transplant. The generation of reactive oxygen species (ROS) during oxidative stress contributes to the occurrence of RIR. Hence, the use of antioxidant compounds can improve oxidative stress due to RIR. This review highlights herbal antioxidant efficacy against RIR injury. The findings of this study indicate that antioxidant compounds with herbal origin could reduce complications due to oxidative stress related to RIR through diminishing lipid peroxidation, decreased production of malondialdehyde (MDA), apoptosis and increasing antioxidant enzymes activity. Reducing oxidative stress with the pharmacological approach of antioxidants can be a desirable target for ameliorating RIR