Abstract
Obesity is a multifactorial disorder and requires favorable environment for its expression. However, some individuals are more prone to weight gain than others in an obesogenic environment. Thus, at individual level, who becomes overweight or obese is mostly determined by genetic factors. The current study was undertaken to explore for the first time the association of the TMEM18 rs7561317 variant with overweight/obesity and related anthropometric, metabolic, physical, and behavioral traits in a sample of Pakistani population with association between the rs7561317 and many traits was not investigated before in any population. The current study involved a total of 612 subjects including 306 overweight/obese and equal number of age- and sex-matched normal weight individuals. Obesity-related parameters were determined and the variant was genotyped by allelic discrimination assay. All the aforementioned associations were assessed by regression analyses adjusted for covariates and corrected for multiple comparisons. The results revealed a significant association of the TMEM18 rs7561317 with overweight/obese phenotype in more than one genetic model. Therefore, h-index (degree of dominance) was calculated, which indicated the recessive mode of inheritance for the above-said association. Similarly, a significant association of the rs7561317 with obesity-related anthropometric traits and clinical surrogate markers of visceral adiposity was observed. Thus, GG genotype of the rs7561317 was found to increase 1.74 times the risk of overweight/obesity in Pakistani population (OR = 1.74, 95% CI 1.210–2.496, p = 0.003) while low physical activity seemed to accentuate the TMEM18 rs7561317-associated risk of overweight/obesity (OR = 2.696, 95% CI 1.485–4.896, p = 0.004).
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Acknowledgements
Authors are thankful to Mr. Adil Anwar Bhatti, Mr. Saad Mirza, and Ms. Soma Rahmani for their contribution in sample collection.
Funding
This work was supported by a recurring grant provided by the International Center for Chemical and Biological Sciences (ICCBS), University of Karachi, Pakistan. However, biochemical assays regarding lipid profile were supported by a research grant given by the Higher Education Commission (HEC) (Ref. No. 5740/Sindh/NRPU/R&D/HEC/2016) under National Research Program for Universities (NRPU). The funding bodies did not play any role in the design of the study, sample collection, data collection, data analysis and interpretation or in writing the manuscript.
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SR conceived the project and arranged funding. AS performed the experiments. AS and SR performed the statistical analysis with major contribution of AS. SR and AS wrote the manuscript with major contribution of SR. SR also has major role in collecting the samples. All authors carefully checked and approved this version of the manuscript.
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Rana, S., Sultana, A. Association of the Variant rs7561317 Downstream of the TMEM18 Gene with Overweight/Obesity and Related Anthropometric Traits in a Sample of Pakistani Population. Biochem Genet 58, 257–278 (2020). https://doi.org/10.1007/s10528-019-09940-2
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DOI: https://doi.org/10.1007/s10528-019-09940-2