The <i>TCN2</i> variant of rs9606756 [Ile23Val] acts as risk loci for obesity‐related traits and mediates by interacting with Apo‐A1

Hebbar, Prashantha; Alkayal, Fadi; Nizam, Rasheeba; Melhem, Motasem; Elkum, Naser; John, Sumi Elsa; Abu‐Farha, Mohamed; Alsmadi, Osama; Thanaraj, Thangavel Alphonse

doi:10.1002/oby.21826

Cited by 15 publications

(9 citation statements)

References 40 publications

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“…Therefore, our findings were not surprising as FTO may interact with ApoA1 in regulating weight, TBW, and SLM and thus affects obesity and also corroborate studies showing SNPs from ApoA1 associated with lower levels of HDL as obesity risk factors (Rashid and Genest, 2007;Chen et al, 2009). In addition, this is also supported by our previous observations showing interactions between Apo-A1/ HDL and a genetic variant in TCN2 regulate WC (Hebbar et al, 2017). Others have demonstrated a positive correlation between ApoB48 and abdominal circumference (Kuo et al, 2019), with obese and hyperlipidemic subjects showing higher levels of ApoB48 (Otokozawa et al, 2009).…”

Section: Discussionsupporting

confidence: 90%

FTO Variant rs1421085 Associates With Increased Body Weight, Soft Lean Mass, and Total Body Water Through Interaction With Ghrelin and Apolipoproteins in Arab Population

et al. 2020

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Association studies have implicated single nucleotide polymorphisms (SNPs), particularly rs1421085, from the fat mass and obesity-associated (FTO) gene with body composition phenotypes, obesity, dietary intake, and physical activity in European, East Asian, and African populations. However, the impact of the rs1421085 variant has not been sufficiently tested in ethnic populations (such as Arabs) with high levels of obesity. Further, there is a lack of studies identifying biomarkers that interact with FTO. Therefore, we investigated the association of rs1421085 with obesity and body composition traits and metabolic biomarkers in Arab population. We genotyped rs1421085 SNP in 278 Arab individuals, where multiple biomarkers relating to obesity, inflammation, and other metabolic pathways were quantified. We performed genetic association tests under additive mode of inheritance using linear regression models and found association of rs1421085_C allele with higher levels of body weight, soft lean mass (SLM), and total body water. Examination (using linear regression models under dominant mode of inheritance) of correlation among biomarkers and interaction with genotypes at the variant revealed that measures of these three body composition traits were found mediated by interaction between carrier genotypes (TC+CC) and measures of ghrelin, ApoA1, and ApoB48. Lean body mass (LBM), to which SLM contributes, is an important determinant of physical strength and is a focal point in studies on sarcopenia. Low LBM is known to be associated with higher risk of cardiometabolic disorders. Thus, the finding on the FTO variant as a genetic determinant of SLM via interaction with ghrelin, ApoA1, and ApoB48 is important.

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Section: Discussionsupporting

confidence: 90%

FTO Variant rs1421085 Associates With Increased Body Weight, Soft Lean Mass, and Total Body Water Through Interaction With Ghrelin and Apolipoproteins in Arab Population

et al. 2020

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“…To the best of our knowledge, the most commonly used Illumina Human OmniExpress Bead Chip genome wide array does not include the tested rs1997623 variant. Apparently, a vast majority of GWA studies were also performed in European, African-American and Asian population and relatively little information is available from the State of Kuwait (Hebbar et al, 2017, 2018). The genetic divergence of Kuwaiti population has largely been evidenced by the differences in disease prevalence and risk allele frequencies.…”

Section: Discussionmentioning

confidence: 99%

Caveolin-1 Variant Is Associated With the Metabolic Syndrome in Kuwaiti Children

Nizam

Al‐Ozairi

Goodson³

et al. 2018

Front. Genet.

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Caveolin-1 (CAV1) variants have been suggested to be associated with obesity and related metabolic disorders, but information based on human studies is limited. In the present study, we aimed to investigate the potential association between the CAV1 rs1997623 C/A variant and metabolic syndrome (MetS) in Kuwaiti children. DNA from saliva samples collected from 1313 Kuwaiti children (mean age: 12 years) were genotyped using the TaqMan SNP genotyping assay. The classification of MetS was based on the presence/absence of four indicators; (1) central obesity, (2) elevated systolic or diastolic blood pressure, (3) low salivary high-density lipoprotein cholesterol (HDLC), and (4) high salivary glucose. In this study, children with MetS scored ≥3, children in the intermediate metabolic group scored 1 or 2 and children without MetS scored 0. About one-third of the children were obese. A total of 246 children (18.7%) were classified as having MetS; 834 children (63.5%) were in the intermediate metabolic group, and 233 children (17.7%) had no indication of MetS. Obesity was highly prevalent in the MetS group (91.9%) while 26.8% of children were obese in the intermediate metabolic group. None of the children were obese in the group without MetS. Analysis of the CAV1 rs1997623 variant revealed a significant association of the A-allele (p = 0.01, Odds Ratio (OR) = 1.66) and the heterozygous CA-genotype (p = 0.005, OR = 1.88) with MetS. Consistently, the A-allele (p = 0.002, OR = 1.71) and CA-genotype (p = 0.005, OR = 1.70) also showed significant association with the intermediate metabolic group. Furthermore, the A-allele (p = 0.01, OR = 1.33) and the CA-genotype (p = 0.008, OR = 1.55) were associated with low levels of saliva HDLC. Individuals who were heterozygous or homozygous for the variant (CA/AA) showed significantly lower levels of high HDLC compared to those harboring the CC-genotype (p = 0.023). Our study revealed a novel association of the CAV1 rs1997623 variant with the MetS and with low saliva HDLC levels in young Kuwaiti children and indicated the need for further in-depth studies to unravel the role of CAV1 gene in the genetic etiology of MetS.

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“…Generally, in genome-wide disease association studies (GWAS), significance is confirmed after adjusting for confounding factors including age, gender, population stratification, and genetic ancestry. In our association analysis, age and gender were only adjusted as all study individuals belong to Arab ethnicity and their population structure has been well-defined in our previous genome-wide association studies 24,31,32. Since all three groups (lean, overweight, and obese) are only of Arabian descent, their haplogroup distribution should be similar to that of the Middle Eastern region.…”

Section: Discussionmentioning

confidence: 99%

“…All participants were recruited after obtaining written informed consent under protocols approved by the Scientific and Ethics Advisory Boards at the Dasman Diabetes Institute, Kuwait. The participant recruitment, sample collection, and related procedures were conducted in accordance with the Declaration of Helsinki and detailed elsewhere 23,24. On categorizing the study subjects based on BMI scores, we ended up with 232 obese (BMI≥30 kg/m 2 ), 110 overweight (BMI≥25 kg/m 2 and <30 kg/m 2 ), and 53 lean (BMI<25 kg/m 2 ) individuals.…”

Section: Methodsmentioning

confidence: 99%

<p>Mitochondrial DNA D-loop sequencing reveals obesity variants in an Arab population</p>

Eaaswarkhanth¹,

Melhem²,

Nizam³

et al. 2019

TACG

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Background: The association of mitochondrial DNA (mtDNA) variations with obesity has been investigated in diverse populations across the world. However, such obesity-associated mtDNA examinations are rarely conducted in Arab populations. Materials and methods: We re-sequenced mtDNA displacement loop (D-loop) region of 395 Arab individuals of Kuwait. We categorized the individuals based on their BMI scores as obese (n=232; BMI ≥30 kg/m 2 ), overweight (n=110; BMI ≥25 kg/m 2 and <30 kg/m 2 ), and lean (n=53; BMI <25 kg/m 2 ). We performed all the statistical tests by combining obese and overweight individuals in one group. Association analyses were conducted applying Fisher's exact test and logistic regression model. Results: We identified that the mtDNA variations m.73A>G, and m.523delAC were positively correlated with obesity, while m.310T>C, and m.16318A>T were negatively associated. All these variants, except m.16318A>T, remain statistically significant after adjusting for age and gender. We found that the variant m.73A>G increases the likelihood of being obese by 6-fold, whereas haplogroup H decreases the probability of being obese in Arab individuals of Kuwait. Haplotype analysis revealed that a haplotype, A263G-C309CT-T310C, defining the H2a clade of H haplogroup, reduces the probability of being obese. Conclusion: Our study reports, for the first time, the obesity-related mtDNA variants in Arabs of Kuwait. Based on the mtDNA D-loop region variations, we detected particular variants and haplogroup that are related with increased and decreased probability of being obese in the Kuwait Arab population.

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The TCN2 variant of rs9606756 [Ile23Val] acts as risk loci for obesity‐related traits and mediates by interacting with Apo‐A1

Abstract: The TCN2 variant acts as a risk factor for WC in the Arab population. The variant mediates obesity-related anthropometric traits via interactions with Apo-A1/high-density lipoprotein or TP53.

Cited by 15 publications

References 40 publications

FTO Variant rs1421085 Associates With Increased Body Weight, Soft Lean Mass, and Total Body Water Through Interaction With Ghrelin and Apolipoproteins in Arab Population

FTO Variant rs1421085 Associates With Increased Body Weight, Soft Lean Mass, and Total Body Water Through Interaction With Ghrelin and Apolipoproteins in Arab Population

Caveolin-1 Variant Is Associated With the Metabolic Syndrome in Kuwaiti Children

<p>Mitochondrial DNA D-loop sequencing reveals obesity variants in an Arab population</p>

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