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

Abstract

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.

Caveolin-1 Genetic Polymorphisms Interact with Fatty Acid Types to Modulate Metabolic Syndrome Risk

“…To the authors' knowledge, there is little evidence describing an association between Cav-1 and metabolic syndrome. It was observed that a genetic variant of Cav-1 (rs3807992) was associated with increased MetS risk, which is consistent with previous studies that revealed a signi cant association between the minor allele in cav-1 variations and the odds of metabolic diseases 10,11,15,17 . Also, compared with other candidate gene studies, no studies had evaluated SNP rs3807992 and MetS risk.…”

“…The exact mechanisms are unclear, but it seems that Cav-1 is able to regulate several key enzymes in lipid metabolism, such as cholesterol ester transfer protein and phospholipid transfer protein 13 . While the association between Cav-1 polymorphisms and type 2 diabetes risk has been widely reported in various populations 14 , these relationships with MetS have been inconsistent, despite several publications on the association between Cav-1 gene variants and serum lipid pro les [14][15][16][17] . To the authors' knowledge, there has been no study evaluating Cav-1 rs3807992 variant, metabolic risk factor, and the interaction of fatty acid intake levels with this SNP.…”

Role of Caveolin-1 in Diabetes and Its Complications

“…CAV1 SNP variants have been suggested to be linked to metabolic syndrome (MetS), a major risk factor for diabetes and coronary artery disease. Several CAV1 single-nucleotide polymorphisms (SNP) were found to associate with MetS: rs926198 in Caucasians and Hispanics [77], rs3807989 in the Chinese Han population [78], and rs1997623 in Kuwaiti children as shown by our previous study [79]. The forest plot in Figure 3 shows an association between LHDLC and MetS with the heterozygous genotype CA and the A-allele, meaning that a carrier of the A genotype has a higher chance of developing MetS in the studied population.…”

Caveolae as Potential Hijackable Gates in Cell Communication

“…Caveolin-1 has been reported to regulate metabolism of lipid droplets in adipocytes (Briand et al, 2014, reviewed in Martin, 2013 and endothelial cells (Kuo et al, 2018), including the composition in peripheral phospholipids and associated proteins (Blouin et al, 2010). CAV-1 gene polymorphisms have been reported in patients with altered lipid metabolism in adult (Mora-Garcia et al, 2017 and juvenile forms (Nizam et al, 2018). Metabolic alterations are partially mediated by impaired insulin signaling (Gonzalez-Munoz et al, 2009;Perez-Verdaguer et al, 2018;Travez et al, 2018).…”