Dataset Information

Polymorphic Analysis of Leptin Promoter in Obese/diabetic Subjects in Kashmiri Population.

ABSTRACT: Background:The role of common variants in leptin promoter has already been established to play a major role in obesity and diabetes in humans. The study was accordingly focused on leptin promoter variants and their potential association with diabetes and obesity in ethnic population from Kashmir, India. Methods:Allele frequencies of 620 Kashmiri subjects with diabetes (200), obese subjects (200), and ethnically matched healthy controls (200) were tested for the Hardy-Weinberg disequilibrium. Among 200 obese subjects, a total of 50 persons were with diabetes. The genotype and allele frequencies were evaluated using the Chi-square or Fisher's exact tests. Results:Sequence analysis revealed two reported variations i.e., rs72563764C>T and rs7799039G>A in promoter region. Both variants show homozygous as well as heterozygous genotypes. These variations indicated significant difference with respect to allelic and genotypic frequencies in all groups i.e., persons with diabetes, obese, and obese persons with diabetes (P < 0.05). We also analyzed the association of these variations with biochemical characteristics and found significant association of rs72563764C>T with triglycerides (TG) in obese patients and fasting plasma glucose (FPG) and random blood sugar (RBS) in obese/persons with diabetes. Also rs7799039G>A showed association with postprandial plasma sugar (PPPS) in obese patients and FPG and resting plasma glucose (RPG) in obese persons with diabetes. Conclusions:Our results are suggestive of the association of leptin promoter gene variations i.e., rs72563764C>T and rs7799039G>A with both diabetes and obesity.

SUBMITTER: Dar R

PROVIDER: S-EPMC6446689 | biostudies-literature | 2019 Jan-Feb

REPOSITORIES: biostudies-literature

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Polymorphic Analysis of Leptin Promoter in Obese/diabetic Subjects in Kashmiri Population.

Dar Rubiya R Rasool Shabhat S Waza Ajaz Ahmad AA Ayoub Gazalla G Qureshi Meenu M Zargar Abdul Hamid AH Bashir Iftikhar I Jan Tariq T Andrabi Khurshid Iqbal KI

Indian journal of endocrinology and metabolism 20190101 1

<h4>Background</h4>The role of common variants in leptin promoter has already been established to play a major role in obesity and diabetes in humans. The study was accordingly focused on leptin promoter variants and their potential association with diabetes and obesity in ethnic population from Kashmir, India.<h4>Methods</h4>Allele frequencies of 620 Kashmiri subjects with diabetes (200), obese subjects (200), and ethnically matched healthy controls (200) were tested for the Hardy-Weinberg dise ...[more]

PMID: 31016164

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Project description:The obese people with abnormal BMI are predisposed to insulin resistance and diabetes. At the same time, human subjects with obesity and high BMI that are otherwise insulin sensitive are an interesting group to study the underlying gene expression patterns which provide them with such protective phenotype. Objective: Insulin resistance (IR) is one of the earliest predictors of type 2 diabetes. However, diagnosis of IR is limited. High fat fed mouse models provide key insights into IR. We hypothesized that early features of IR are associated with persistent changes in gene expression (GE) and endeavoured to (a) develop novel methods for improving signal:noise in analysis of human GE using mouse models; (b) identify a GE motif that accurately diagnoses IR in humans; and (c) identify novel biology associated with IR in humans. Methods: We integrated human muscle GE data with longitudinal mouse GE data and developed an unbiased three-level cross-species analysis platform (single-gene, gene-set and networks) to generate a gene expression motif (GEM) indicative of IR. A logistic regression classification model validated GEM in 3 independent human datasets (n =115). Results: This GEM of 93 genes substantially improved diagnosis of IR compared to routine clinical measures across multiple independent datasets. Individuals misclassified by GEM possessed other metabolic features raising the possibility that they represent a separate metabolic subclass. The GEM was enriched in pathways previously implicated in insulin action and revealed novel associations between Î²-catenin and Jak1 and IR. Functional analyses using small molecule inhibitors showed an important role for these proteins in insulin action. Conclusions: This study shows that systems approaches for identifying molecular signatures provides a powerful way to stratify individuals into discrete metabolic groups. Moreover, we speculate that the Î²-catenin pathway may represent a novel biomarker for IR in humans that warrant future investigation. Gene expression from muscle biopsies of Lean, Obese insulin sensitive (OIS), Obese insulin resistant (OIR) and obese T2D patients (T2D) were compared for differential expression between the groups (n=7 in each group)

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Dataset Information

Polymorphic Analysis of Leptin Promoter in Obese/diabetic Subjects in Kashmiri Population.

Publications

Polymorphic Analysis of Leptin Promoter in Obese/diabetic Subjects in Kashmiri Population.

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