Caveolin-1 rs1997623 variant and adult metabolic syndrome—Assessing the association in three ethnic cohorts of Arabs, South Asians and South East Asians

Abstract

Background: Animal and cell model studies have implicated CAV1 in the pathophysiology of metabolic disorders. Our previous studies demonstrated a potential association of CAV1 rs1997623 C/A variant with pediatric metabolic syndrome (MetS) in Arab children. In the present study, we evaluate whether the CAV1 variant associates with MetS Arab adults as well. The association signal is further examined for ancestry-specific variation by considering cohorts of other ethnicities.Method: The CAV1 rs1997623 was genotyped in three cohorts of Arab (n = 479), South Asian (n = 660), and South East Asian (n = 362) ethnic adults from Kuwait. MetS status of the individuals was diagnosed using the IDF criteria (presence of central obesity and at least two abnormalities out of: elevated TG, low HDL, hypertension, or T2D). 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 MetS traits were assessed using linear and logistic regression models adjusted for age and sex. In addition, empirical p-values (Pemp) were generated using max(T) permutation procedure based on 10,000 permutations.Results: The CAV1 variant was significantly associated with MetS status (OR = 1.811 [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 association was weak and insignificant in the South Asian and South East Asian cohorts (OR = 1.19 and 1.11; p-values = 0.25 and 0.67, respectively).Conclusion: The reported association of CAV1 rs1997623 C/A with MetS in Arab pediatric population is now demonstrated in an adult Arab cohort as well. The weak association signal seen in the Asian cohorts lead us to propose a certain extent of ethnic-specificity in CAV1 rs1997623 association with MetS.

Caveolin-1 rs1997623 Single Nucleotide Polymorphism Creates a New Binding Site for the Early B-Cell Factor 1 That Instigates Adipose Tissue CAV1 Protein Overexpression

“…Little is known about CAV1 regulation in adipocytes; single nucleotide polymorphisms (SNPs) in the CAV1 gene have been associated with metabolic syndrome (MetS), which is a major risk factor for diabetes and coronary artery disease. Several CAV1 SNPs were found to be associated with MetS, including rs926198 in Caucasians and Hispanics [ 11 ], rs3807989 in Han Chinese [ 12 ], rs11773845 in Latin Americans [ 13 ], rs3807992 in Persians [ 14 ], and rs1997623 in Kuwaiti children, as shown in our previous study [ 15 ], and as found in another adult population [ 16 ]. Although central obesity is a landmark trait for the diagnosis of MetS, the full spectrum of traits relating to MetS includes various other metabolic factors related to hypertension, diabetes, and dyslipidemia.…”

Editorial: Population and ancestry specific variation in disease susceptibility

“…Overall, this Research Topic collected four articles ( Al Madhoun et al, 2022 ; Cullina et al, 2023 ; James et al, 2023 ; Sezgin and Kaplan, 2022 ).…”

“…Thus, this Research Topic presents a series of research works on population-specific variation in human diseases ( Al Madhoun et al, 2022 ; Cullina et al, 2023 ; James et al, 2023 ; Sezgin and Kaplan, 2022 ). The complementary Research Topic in Frontiers in Genetics named “High-throughput Sequencing-based Investigation of Chronic Disease Markers and Mechanisms, Volume II” ( https://www.frontiersin.org/research-topics/53085/high-throughput-sequencing-based-investigation-of-chronic-disease-markers-and-mechanisms-volume-ii ) continues the collection of articles on the markers of human diseases ( Orlov et al, 2022 ).…”