Risk variants of obesity associated genes demonstrate BMI raising effect in a large cohort.

Autor:	Saqlain M; University Institute of Biochemistry & Biotechnology, PMAS- Arid Agriculture University Rawalpindi, Rawalpindi, Pakistan.; Department of Biochemistry and Molecular Biology, University of Sialkot, Sialkot, Pakistan., Khalid M; University Institute of Biochemistry & Biotechnology, PMAS- Arid Agriculture University Rawalpindi, Rawalpindi, Pakistan., Fiaz M; Department of Pathology, Pakistan Institute of Medical Sciences (PIMS), Islamabad, Pakistan., Saeed S; University Institute of Biochemistry & Biotechnology, PMAS- Arid Agriculture University Rawalpindi, Rawalpindi, Pakistan., Mehmood Raja A; University Institute of Biochemistry & Biotechnology, PMAS- Arid Agriculture University Rawalpindi, Rawalpindi, Pakistan., Mobeen Zafar M; University Institute of Biochemistry & Biotechnology, PMAS- Arid Agriculture University Rawalpindi, Rawalpindi, Pakistan., Fatima T; Department of Rheumatology and Inflammation Research, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden., Bosco Pesquero J; Center for Research and Molecular Diagnostic of Genetic Diseases-Department of Biophysics, Federal University of São Paulo, São Paulo, Brazil., Maglio C; Department of Rheumatology and Inflammation Research, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.; Region Västra Götaland, Sahlgrenska University Hospital, Rheumatology Clinic, Gothenburg, Sweden.; Wallenberg Center for Molecular and Translational Medicine, University of Gothenburg, Gothenburg, Sweden., Valadi H; Department of Rheumatology and Inflammation Research, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden., Nawaz M; Department of Rheumatology and Inflammation Research, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden., Kaukab Raja G; University Institute of Biochemistry & Biotechnology, PMAS- Arid Agriculture University Rawalpindi, Rawalpindi, Pakistan.
Jazyk:	angličtina
Zdroj:	PloS one [PLoS One] 2022 Sep 20; Vol. 17 (9), pp. e0274904. Date of Electronic Publication: 2022 Sep 20 (Print Publication: 2022).
DOI:	10.1371/journal.pone.0274904
Abstrakt:	Obesity is highly polygenic disease where several genetic variants have been reportedly associated with obesity in different ethnicities of the world. In the current study, we identified the obesity risk or protective association and BMI raising effect of the minor allele of adiponectin, C1Q and collagen domain containing (ADIPOQ), cholesteryl ester transfer protein (CEPT), FTO alpha-ketoglutarate dependent dioxygenase (FTO), leptin (LEP), and leptin receptor (LEPR) genes in a large cohort stratified into four BMI-based body weight categories i.e., normal weight, lean, over-weight, and obese. Based on selected candidate genetic markers, the genotyping of all study subjects was performed by PCR assays, and genotypes and allele frequencies were calculated. The minor allele frequencies (MAFs) of all genetic markers were computed for total and BMI-based body weight categories and compared with MAFs of global and South Asian (SAS) populations. Genetic associations of variants with obesity risk were calculated and BMI raising effect per copy of the minor allele were estimated. The genetic variants with higher MAFs in obese BMI group were; rs2241766 (G = 0.43), rs17817449 (G = 0.54), rs9939609 (A = 0.51), rs1421085 (C = 0.53), rs1558902 (A = 0.63), and rs1137101 (G = 0.64) respectively. All these variants were significantly associated with obesity (OR = 1.03-4.42) and showed a high BMI raising effect (β = 0.239-0.31 Kg/m2) per copy of the risk allele. In contrast, the MAFs of three variants were higher in lean-normal BMI groups; rs3764261 A = 0.38, rs9941349 T = 0.43, and rs7799039 G = 0.40-0.43). These variants showed obesity protective associations (OR = 0.68-0.76), and a BMI lowering effect per copy of the protective allele (β = -0.103-0.155 Kg/m2). The rs3764261 variant also showed significant and positive association with lean body mass (OR = 2.38, CI = 1.30-4.34). Overall, we report six genetic variants of ADIPOQ, FTO and LEPR genes as obesity-risk markers and a CETP gene variant as lean mass/obesity protective marker in studied Pakistani cohort. Competing Interests: The authors have declared that no competing interests exist.
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu