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

Publisher: Public Library of Science Country of Publication: United States NLM ID: 101285081 Publication Model: eCollection Cited Medium: Internet ISSN: 1932-6203 (Electronic) Linking ISSN: 19326203 NLM ISO Abbreviation: PLoS One Subsets: MEDLINE

Original Publication: San Francisco, CA : Public Library of Science

Dioxygenases*/genetics ; Leptin*/genetics; Adiponectin/genetics ; Alpha-Ketoglutarate-Dependent Dioxygenase FTO/genetics ; Body Mass Index ; Body Weight/genetics ; Cholesterol Ester Transfer Proteins/genetics ; Complement C1q/genetics ; Genetic Markers ; Humans ; Ketoglutaric Acids ; Obesity/genetics ; Polymorphism, Single Nucleotide ; Receptors, Leptin/genetics

Competing Interests: The authors have declared that no competing interests exist.
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.

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0 (Adiponectin)
0 (Cholesterol Ester Transfer Proteins)
0 (Genetic Markers)
0 (Ketoglutaric Acids)
0 (Leptin)
0 (Receptors, Leptin)
80295-33-6 (Complement C1q)
EC 1.13.11.- (Dioxygenases)
EC 1.14.11.33 (Alpha-Ketoglutarate-Dependent Dioxygenase FTO)
EC 1.14.11.33 (FTO protein, human)

Date Created: 20220920 Date Completed: 20220923 Latest Revision: 20221004

20250114

PMC9488755

10.1371/journal.pone.0274904

36126070