{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T02:40:48Z","timestamp":1760150448830,"version":"build-2065373602"},"reference-count":43,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2023,11,21]],"date-time":"2023-11-21T00:00:00Z","timestamp":1700524800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Deputyship for Research and Innovation, \u201cMinistry of Education\u201d in Saudi Arabia","award":["IFKSUOR3-193-1"],"award-info":[{"award-number":["IFKSUOR3-193-1"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>The genetic etiology of Keratoconus (KC) in Middle Eastern Arabs of Saudi origin is still unclear. A recent genome-wide study identified two significant loci in the region of PNPLA2 (rs61876744) and CSNK1E (rs138380) for KC that may be associated with KC in the Saudi population. In addition, polymorphisms in the apolipoprotein E (APOE) gene, namely, rs429358 and rs7412, responsible for APOE allelic variants \u03b52, \u03b53, and \u03b54, may influence KC via oxidative stress mechanism(s). Thus, we investigated the possible association of polymorphisms rs61876744, rs138380, rs429358, rs7412, and APOE genotypes in KC patients of the Saudi population. This study included 98 KC cases and 167 controls. Polymorphisms rs6187644 and rs138380 were genotyped using TaqMan assays, and rs429358 and rs7412 were genotyped via Sanger sequencing. Although the allele frequency of rs61876744(T) in PNPLA2 was a protective effect against KC (odds ratio (OR) = 0.64, 95% confidence interval (CI) = 0.44\u20130.93), the p-value (p = 0.020) was not significant for multiple testing correction (p = 0.05\/4 = 0.015). However, rs6187644 genotype showed a modestly significant protective effect in the dominant model (OR = 0.53, 95% CI = 0.32\u20130.88, p = 0.013). Polymorphisms rs138380, rs429358, and rs7412 showed no significant allelic or genotype association with KC. However, the \u03b52-carriers (\u03b52\/\u03b52 and \u03b52\/\u03b53 genotypes) exhibited a greater than 5-fold increased risk of KC, albeit non-significantly (p = 0.055). Regression analysis showed no significant effect of age, gender, and the four polymorphisms on KC. Our results suggest that polymorphism rs6187644 in PNPLA2 might be associated with KC in the Middle Eastern Arabs of Saudi origin but warrant a large-scale association analysis at this locus.<\/jats:p>","DOI":"10.3390\/genes14122108","type":"journal-article","created":{"date-parts":[[2023,11,21]],"date-time":"2023-11-21T01:48:45Z","timestamp":1700531325000},"page":"2108","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Association between Polymorphism rs61876744 in PNPLA2 Gene and Keratoconus in a Saudi Cohort"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5516-6951","authenticated-orcid":false,"given":"Altaf A.","family":"Kondkar","sequence":"first","affiliation":[{"name":"Department of Ophthalmology, College of Medicine, King Saud University, Riyadh 11411, Saudi Arabia"},{"name":"Glaucoma Research Chair in Ophthalmology, College of Medicine, King Saud University, Riyadh 11411, Saudi Arabia"},{"name":"King Saud University Medical City, King Saud University, Riyadh 11411, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Taif A.","family":"Azad","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, College of Medicine, King Saud University, Riyadh 11411, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tahira","family":"Sultan","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, College of Medicine, King Saud University, Riyadh 11411, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9320-5579","authenticated-orcid":false,"given":"Tanvir","family":"Khatlani","sequence":"additional","affiliation":[{"name":"Department of Blood and Cancer Research, King Abdullah International Medical Research Center, King Saud Bin Abdulaziz University of Health Sciences, Ministry of National Guard Health Affairs, Riyadh 11426, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Abdulaziz A.","family":"Alshehri","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Imam Abdulrahman Alfaisal Hospital, Riyadh 14723, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Glenn P.","family":"Lobo","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology and Visual Neurosciences, University of Minnesota, Minneapolis, MN 55347, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1831-6807","authenticated-orcid":false,"given":"Hatem","family":"Kalantan","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, College of Medicine, King Saud University, Riyadh 11411, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0573-4017","authenticated-orcid":false,"given":"Saleh A.","family":"Al-Obeidan","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, College of Medicine, King Saud University, Riyadh 11411, Saudi Arabia"},{"name":"Glaucoma Research Chair in Ophthalmology, College of Medicine, King Saud University, Riyadh 11411, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Abdulrahman M.","family":"Al-Muammar","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, College of Medicine, King Saud University, Riyadh 11411, Saudi Arabia"},{"name":"King Saud University Medical City, King Saud University, Riyadh 11411, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,11,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1038\/eye.2013.278","article-title":"The pathogenesis of keratoconus","volume":"28","author":"Davidson","year":"2014","journal-title":"Eye"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"533","DOI":"10.1097\/APO.0000000000000332","article-title":"Biochemical markers and alterations in keratoconus","volume":"9","author":"Shetty","year":"2020","journal-title":"Asia Pac. 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