Comprehensive review and annotation of susceptibility SNPs associated with obesity-related traits.

We aimed to summarize the results of genetic association studies for obesity and provide a comprehensive annotation of all susceptibility single nucleotide polymorphisms (SNPs). A total of 72 studies were summarized, resulting in 90,361 susceptibility SNPs (738 index SNPs and 89,623 linkage disequilibrium SNPs). Over 90% of the susceptibility SNPs are located in non-coding regions, and it is challenging to understand their functional significance. Therefore, we annotated these SNPs by using various functional databases. We identified 24,623 functional SNPs, including 4 nonsense SNPs, 479 missense SNPs, 399 untranslated region SNPs which might affect microRNA binding, 262 promoter and 5,492 enhancer SNPs which might affect transcription factor binding, 7 splicing sites, 76 SNPs which might affect gene methylation levels, 1,839 SNPs under natural selection and 17,351 SNPs which might modify histone binding. Expression quantitative trait loci analyses for functional SNPs identified 98 target genes, including 69 protein coding genes, 27 long non-coding RNAs and 3 processed transcripts. The percentage of protein coding genes that could be correlated with obesity-related pathways directly or through gene-gene interaction is 75.36 (52/69). Our results may serve as an encyclopaedia of obesity susceptibility SNPs and offer guide for functional experiments.

The aberrant expression of Smad6 and TGF-ß in obesity linked cardiac disease.

OBJECTIVE: Obesity is a major health problem in modern society because their progression is always associated with many health issues. The major among them is developing the cardiovascular disease because as the obesity prolonged it results with cardiac remodelling and finally results in the dysfunction of the cardiac system. Many genes are associated with developing the obesity-linked cardiac dysfunction and it should be evaluated at different pathological stages of obesity. MATERIALS AND METHODS: In the present studies, we analyzed the expression pattern of Smad6 and TGF-ß using obesity-induced mice model which are ob/ob-/- deficient. The pathology of disease progression in initial and aggressive stage of cardiac dysfunction are studied together with Smad6 and TGF-ß expression. RESULTS: The mice develop initial stages of cardiac dysfunction on 3rd month and advanced stage of cardiac dysfunction on the 6th month. The results with histology show as the dysfunction progress it shows cellular lesions associated with enlarged cells. Immunochemistry with Smad6 represents that its expression positively regulate and repair the initial lesion but it has no role in the aggressive form of cardiac dysfunction and at that stage their expression downregulated. The results with TGF-ß show initial upregulation in repairing the damage but in latter stage its expression many fold increases and it takes part in the inflammatory response. CONCLUSIONS: Overall our results show aberrant expression of Smad6 and TGF-ß at different stages of obesity linked cardiac dysfunction.