Abstract
Genetic variations in a disintegrin and metalloprotease 12 (ADAM12) gene may contribute to develop Osteoarthritis (OA) that is characterized by cartilage matrix degradation and osteophytes formation. Therefore, the aim of present study was to analyze the association between the ADAM12 gene variants and knee OA predisposition. Tetra‐primers ARMS‐PCR was employed, to genotype the ADAM12 gene polymorphisms (rs1044122 and rs1871054) in 400 knee OA patients and equal number of age-matched controls. The association between ADAM12 gene variants and OA susceptibility was estimated using the Chi-square, logistic regression, haplotypes and linkage analyses. A significant association of rs1044122 (genotype: χ2 = 18.94; P < 0.001, allele: χ2 = 19.10; P < 0.001) and rs1871054 (genotype: χ2 = 10.04; P = 0.007, allele: χ2 = 10.57; P = 0.001) was observed with increased OA susceptibility. The variant genotype of rs1044122 increased OA risk more than twice [odds ratio (OR) 2.20; P = 0.001] and the risk was higher in females (OR 2.43; P = 0.001). The variant genotype of rs1871054 was perceived to almost double the risk in females (OR 1.97; P = 0.003). Moreover, a significant association of rs1044122 and rs1871054 under the additive genetic model (P < 0.001 and P = 0.002, respectively) was observed. The targeted ADAM12 gene polymorphisms, showed significant association with knee OA susceptibility. Females harboring the polymorphisms might be at risk. Besides, the haplotype CC of rs1044122 and rs1871054 in the ADAM12 gene may double knee OA risk. These findings may help in determining the etiology of OA and recognizing the people at risk of developing knee OA.
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Data Availability
The datasets analyzed during this study may be provided on reasonable request from the corresponding author.
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The authors acknowledge Dr. Muhammad Saeed Minhas, Orthopedic Surgeon in the JPMC, for collaboration and support.
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SF, BK: Conception and design of work. SF, BK, OYK: Data analyses and interpretation. BK, MA: Drafting of the manuscript. SF, SZ, OYK: Revision of the manuscript. AA, OYK, SF: Final approval of the manuscript to be published.
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All procedures performed in the study involving human participants were under the ethical standards of the Helsinki declaration (1964 and its later amendments). The institutional ethics committee of Jinnah Postgraduate Medical Centre (JPMC), Karachi and the Karachi Institute of Biotechnology and Genetic Engineering (KIBGE), Pakistan, has approved the study. All the samples have been collected with written informed consent.
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Fatima, S., Khan, B., Khan, O.Y. et al. Tetra-primers ARMS-PCR Based Association Analyses of Synonymous and Intronic Variants in the ADAM12 Gene with Susceptibility to Knee Osteoarthritis: A Case-Control Study. Biochem Genet 60, 1695–1715 (2022). https://doi.org/10.1007/s10528-022-10189-5
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DOI: https://doi.org/10.1007/s10528-022-10189-5