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.
Objective: The family of angiopoietin-like proteins (ANGPTLs) is composed of eight ANGPTLs members that are involved in regulating various metabolic processes and have been implicated in type 2 diabetes (T2D) and obesity. ANGPTL5 is an understudied member of this family that has been suggested to regulate triglyceride metabolism with a potential role in obesity. This study was designed to investigate the expression levels of ANGPTL5 protein in the circulation of subjects with obesity and T2D. Methods: A total of 204 subjects were enrolled in this cross-sectional study, of which 95 had diagnosed T2D and 109 did not (non-T2D). Within the non-T2D group, 39 subjects were obese (BMI ≥ 30 Kg/m 2 ) and 70 were not (BMI < 30 Kg/m 2 ). Among subjects with T2D, 61 were obese and 34 were non-obese. Circulating ANGPTL5 plasma levels were measured by enzyme-linked immunosorbent assay (ELISA). Results: In this study, we showed that ANGPTL5 levels were higher in the plasma of subjects with T2D [mean ± standard error of the mean (SEM): 5.78 ± 2.70 ng/mL] compared with individuals without T2D (mean ± SEM: 4.42 ± 2.22 ng/mL; P < 0.001). Obese and non-T2D subjects had significantly higher levels of ANGPTL5 (mean ± SEM: 5.115 ± 0.366 ng/mL) compared with non-obese, non-T2D subjects (mean ± SEM: 4.02 ± 0.271 ng/mL; P = 0.003). Similarly, among subjects with diagnosed T2D, those who were obese had higher ANGPTL5 plasma levels than non-obese subjects, although this difference did not reach statistical significance ( P = 0.088). Correlation analyses revealed that ANGPTL5 levels positively associated with fasting plasma glucose (FPG), glycated hemoglobin (HbA1c), triglycerides (TGL), and insulin resistance as measured by HOMA-IR. Conclusion: our data shows for the first time that circulating ANGPTL5 levels were higher in obese individuals and those with T2D. Further analysis will be required to better understand the interaction between ANGPTL5 and other metabolic related biomarkers to shed more light on its role in diabetes and obesity.
Angiopoetin like protein family is composed of eight members that are involved in regulating various metabolic processes. ANGPTL5 is one of the members of this family that is mainly expressed in the heart and was showed to stimulate the expansion of human cord blood hematopoietic stem cell ex-vivo. This study was designed to investigate the expression level of this protein in the plasma of obese and diabetic people. Methods: A total of 204 people were enrolled in this study including 109 nondiabetic and 95 type 2 diabetics. The nondiabetic people included 70 non-obese (BMI<30 Kg/m2) and 39 obese people (BMI<30 Kg/m2), while the diabetic people included 34 non-obese and 61 obese people. ANGPTL5 plasma level was measured by ELISA. Results: In this study we showed that ANGPTL5 level was increased in the plasma of diabetic people (5.78±2.59 ng/mL) compared to nondiabetics (4.42 ± 2.32 ng/mL) (p-Value<0.0001). Obese nondiabetics had a significantly higher level of ANGPTL5 (5.12±2.23 ng/mL) compared to non-obese people (4.02 ± 2.27 ng/mL) (p-Value=0.029). Obese diabetic had higher level of ANGPTL5 compared non-obese yet did not reach significance (p-Value=0.064). ANGPTL5 was significantly associated with glycated haemoglobin 1C and insulin resistance as measured by HOMA-IR. Conclusion: Our data shows for the first time that ANGPTL5 was increased in diabetic and obese people. Given its unique tissue expression in the heart, ANGPTL5 might modulate its response to insulin resistance through its interaction with other proteins including other ANGPTL proteins. Further analysis will be required to better understand the interaction between ANGPTL5 and other metabolic related biomarkers to shed more light on its role in diabetes and obesity. Disclosure N. Alhasawi: None. M. Qaddoumi: None. F. Almulla: None. J. Tuomilehto: None. M. Alanbaei: None. J. Abubaker: None.
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