Studies have implicated CAV1 in the pathophysiology of diabetes and obesity. Previously, we demonstrated a potential association between the CAV1 rs1997623 C/A variant and metabolic syndrome (MetS) in Kuwaiti children. In the present study, we substantiate the association of CAV1 with MetS in adult Arab individuals. Method: The CAV1 rs1997623 was genotyped in three cohorts of Arabs (n=479) , South Asians (n=660) and South East Asians (n=362) . MetS status of the individuals was diagnosed using the IDF criteria (i.e., presence of central obesity and of at least two abnormalities of high TG, low HDL, hypertension, or type 2 diabetes) . The quantitative measure of MetS was calculated as siMS=2*WC/Height + FBG/5.6 + TG/1.7 + SBP/130 - HDL/1.02 for males or HDL/1.28 for females. Allelic associations with quantitative and dichotomous traits were assessed using linear and logistic regression, respectively, with and adjustment for age and sex. CAV1 transcripts were quantified in adipose tissues from a cohort of 50 Arab individuals differing in siMS score. Results: The CAV1 variant was significantly associated with MetS status (OR=1.8[1.25-2.61]; P-value=0.0015; Pemp=0.0013) and with siMS (Effect size = 0.206; P-value=0.0035; Pemp=0.0028) in the cohort of Arab individuals. The variant was weakly and insignificantly associated in the cohorts of South Asian and South East Asian individuals (OR= 1.and 1.11; P-values= 0.25 and 0.67, respectively) . siMS scores correlated positively with mRNA levels of CAV1 in adipose tissue. Conclusion: The association of CAV1 rs1997623 C/A with MetS in Arab pediatric is now demonstrated in adults as well. Higher expression levels were seen in individuals poses increasing MetS rates further validates the implication of CAV1 rs1997623 C/A variant in MetS phenotype. Only a weak association signal was seen in the South Asian and South East Asian populations leading us to propose that the CAV1 rs1997623 association with MetS is probably specific to Arab ethnicity.
A.Al madhoun: None. P.Hebbar: None. R.Nizam: None. D.Haddad: None. M.H.Dashti: None. M.Abu-farha: None. R.Ahmad: None. A.T.Thangavel: None. F.Almulla: None.
Kuwait Foundation for the Advancement of Sciences (KFAS) and Dasman Diabetes Institute, Project RA CB-2021-007