AUTHOR=Al Madhoun Ashraf , Hebbar Prashantha , Nizam Rasheeba , Haddad Dania , Melhem Motasem , Abu-Farha Mohamed , Thanaraj Thangavel Alphonse , Al-Mulla Fahd 

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

JOURNAL=Frontiers in Genetics

VOLUME=13

YEAR=2022

URL=https://www.frontiersin.org/journals/genetics/articles/10.3389/fgene.2022.1034892

DOI=10.3389/fgene.2022.1034892

ISSN=1664-8021

ABSTRACT=<p><bold>Background:</bold> Animal and cell model studies have implicated <italic>CAV1</italic> in the pathophysiology of metabolic disorders. Our previous studies demonstrated a potential association of <italic>CAV1</italic> rs1997623 C/A variant with pediatric metabolic syndrome (MetS) in Arab children. In the present study, we evaluate whether the <italic>CAV1</italic> variant associates with MetS Arab adults as well. The association signal is further examined for ancestry-specific variation by considering cohorts of other ethnicities.</p><p><bold>Method:</bold> The <italic>CAV1</italic> rs1997623 was genotyped in three cohorts of Arab (<italic>n</italic> = 479), South Asian (<italic>n</italic> = 660), and South East Asian (<italic>n</italic> = 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 <italic>p-</italic>values (P<sub><italic>emp</italic></sub>) were generated using max(T) permutation procedure based on 10,000 permutations.</p><p><bold>Results:</bold> The <italic>CAV1</italic> variant was significantly associated with MetS status (OR = 1.811 [1.25–2.61]; <italic>p</italic>-value = 0.0015; P<sub><italic>emp</italic></sub> = 0.0013) and with siMS (Effect size = 0.206; <italic>p</italic>-value = 0.0035; P<sub><italic>emp</italic></sub> = 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; <italic>p</italic>-values = 0.25 and 0.67, respectively).</p><p><bold>Conclusion:</bold> The reported association of <italic>CAV1</italic> 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 <italic>CAV1</italic> rs1997623 association with MetS.</p>