No abstract

The present findings suggest that MTHFR 1298 A > C polymorphism and, altered homocysteine and vitamin B levels might play a vital role in the precipitation of vitiligo.

The present study proposes the crucial role of CAT and its allelic variants in oxidative stress-mediated pathogenesis of vitiligo.

Vitiligo is characterized by circumscribed depigmented macules in the skin resulting due to the autoimmune destruction of melanocytes from the epidermis. Both humoral as well as cell-mediated autoimmune responses are involved in melanocyte destruction. Several studies including ours have established that oxidative stress is involved in vitiligo onset, while autoimmunity contributes to the disease progression. However, the underlying mechanism involved in programing the onset and progression of the disease remains a conundrum. Based on several direct and indirect evidences, we suggested that endoplasmic reticulum (ER) stress might act as a connecting link between oxidative stress and autoimmunity in vitiligo pathogenesis. Oxidative stress disrupts cellular redox potential that extends to the ER causing the accumulation of misfolded proteins, which activates the unfolded protein response (UPR). The primary aim of UPR is to resolve the stress and restore cellular homeostasis for cell survival. Growing evidences suggest a vital role of UPR in immune regulation. Moreover, defective UPR has been implicated in the development of autoimmunity in several autoimmune disorders. ER stress-activated UPR plays an essential role in the regulation and maintenance of innate as well as adaptive immunity, and a defective UPR may result in systemic/tissue level/organ-specific autoimmunity. This review emphasizes on understanding the role of ER stress-induced UPR in the development of systemic and tissue level autoimmunity in vitiligo pathogenesis and its therapeutics.

Adiponectin is a prime determinant of the status of insulin resistance. Association studies between adiponectin (ADIPOQ) gene single nucleotide polymorphisms (Snps) and metabolic diseases have been reported earlier. However, results are ambiguous due to apparent contradictions. Hence, we investigated (1) the association between ADIPOQ Snps: −11377C/G, +10211T/G, +45T/G and +276G/T for the risk towards type 2 diabetes (T2D) and, (2) genotype-phenotype association of these SNPs with various biochemical parameters in two cohorts. Genomic DNA of diabetic patients and controls from Gujarat and, Jammu and Kashmir (J&K) were genotyped using PCR-RFLP, TaqMan assay and MassArray. transcript levels of ADIPOQ were assessed in visceral adipose tissue samples, and plasma adiponectin levels were estimated by qPCR and ELISA respectively. Results suggest: (i) reduced HMW adiponectin/ total adiponectin ratio in Gujarat patients and its association with +10211T/G and +276G/T, and reduced ADIPOQ transcript levels in T2D, (ii) association of the above SNPs with increased FBG, BMI, TG, TC in Gujarat patients and (iii) increased GGTG haplotype in obese patients of Gujarat population and, (iv) association of −11377C/G with T2D in J&K population. Reduced HMW adiponectin, in the backdrop of obesity and ADIPOQ genetic variants might alter metabolic profile posing risk towards T2D.Metabolic Syndrome (MS) is the new wave of diseases that has hit the human population in the last few decadesthe Metabolic Syndrome Era. It has become pandemic and with obesity and type 2 diabetes (T2D) clubbed under the MS umbrella, millions of people around the globe have come under its grip. Though obesity and T2D are ubiquitous, there exists a pattern of prevalence based on ethnicity. A recent report has identified demographic transitions, nutrition and lifestyle in the backdrop of genetic predisposition as the chief factors responsible for the rising trend of obesity associated amongst South Asians 1 . Over accumulation of visceral adipose tissue (AT) has been identified as one of the major driving factors towards T2D. Adipose tissue is an important regulator of metabolic homeostasis by virtue of the adipokines (pro-inflammatory and anti-inflammatory) that it secretes. In obese conditions, the fine-tuned balance between the pro-and anti-inflammatory adipokines gets altered leading to various metabolic disorders 2 . These bioactive peptides act locally and distally to calibrate and fine tune various metabolic pathways. Adiponectin is one such calibrator which is abundantly expressed in white adipose tissue 3 . It circulates in three polymorphic forms, low molecular weight (LMW), moderate molecular weight (MMW) and high molecular weight (HMW). Interestingly, the ratio of plasma HMW adiponectin to total adiponectin is more strongly correlated with plasma glucose levels than any of the forms alone 4 . Adiponectin gene (ADIPOQ/ APM1/GBP28) locus, 3q27, has been strongly associated with a variety of metabolic disorders like-impaired glucose tolerance, obesity, dys...