Document Details
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Document Type |
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Thesis |
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Document Title |
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GENETIC VARIATIONS OF CYTOCHROME P450 EPOXYGENASE (CYP2J2, CYP2C9), AND PROSTAGLANDIN GENE IN RELATION TO MULTIPLE SCLEROSIS RISK التغيرات الوراثية للسيتوكروم ب450 أيبوأكسجيناز(CYP2J2, CYP2C9)، وجين البروستاجلاندين وعلاقتها بخطر مرض التصلب المتعدد |
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Subject |
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Faculty of Science |
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Document Language |
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Arabic |
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Abstract |
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Multiple sclerosis (MS) is a neurological disease that is characterized by demyelination, inflammation, and loss of axonal. Eicosanoids are specific biomarkers of inflammation. Free arachidonic acid (AA) can be metabolized to eicosanoids by cyclooxygenase (COX-2), lipoxygenases (LOX), and cytochrome P450 enzymes. The COX-2 is an inducible enzyme that plays a major role in the inflammatory response by converting AA to prostaglandins (PGs). AA can be metabolized by cytochrome P450 epoxygenases CYP2C9 and CYP2J2 to epoxyeicosatrienoic acids (EETs), which has been established to has anti-inflammatory. Furthermore, EETs are important endogenous brain lipid signaling molecules involved in the regulation of many facets of CNS function. This suggests that genetic alterations of cytochrome P450 epoxygenases might affect the activity of EETs which determine susceptibility to the development of MS. Therefore, we aimed to investigate the possible association between the genetic variations of COX-2, CYP2J2, and CYP2C9 and the risk of MS. The study was conducted on 40 MS patients and 20 controls. Genotyping was performed by polymerase chain reaction (PCR) and sanger sequencing. In this study, a synonymous substitution of Valine at position 102 (rs5277) in COX-2 within exon 3 was detected in 2/40 (5%) patients and 1/20 (5%) controls. In exon 2 of CYP2J2 gene three SNPs were detected, namely rs11572245 (c.373+173C>G), rs3738474 (c.373+26C>T), and rs3820538 (c.211-125C>T). The rs11572245 was detected in 2/40 (5%) patients and 6/20 (30%) controls. The rs3738474 was detected in 1/40 (2.5%) patient and 3/20 (15%) controls. The rs3820538 was detected in 4/40 (10%) patients and 6/20 (30%) controls. One missense substitution (rs2228113, Asn124Ser), synonymous variant (Pro112=), and SNP rs11572244 were detected at exon 2 in control samples only. Two SNPs were detected in exon 4 of the CYP2J2 gene. One of the two SNPs was novel variant C/A at chromosome position (1:59912077). This polymorphism was detected in 11/40 (27.5%) patients and 6/20 (30%) controls. The SNP rs75173289 was detected in 2/40 (5%) patients and 1/20 (5%) control. In exon 4 of CYP2C9 gene one SNP CYP2C9C-65 (rs9332127) was detected in 1/40 (2.5%) patient and 3/20 (15%) controls. In exon 7 of CYP2C9 two CYP2C9 alleles, namely CYP2C9*3 and CYP2C9*11 were detected. The CYP2C9*3 (rs1057910) missense substitution of isoleucine to leucine change at codon 359 (Ile359Leu) was detected in 5/40 (12.5%) as heterozygous and 1/40 (2.5%) as homozygous in MS patients. The CYP2C9*11 allele (rs28371685) missense substitution of arginine to tryptophan substitution at codon 335 (Arg335Trp) was detected in 1/40 (2.5%) as heterozygous in MS patients. A novel mutation with an insertion of C in chromosome position 10:94981146 in exon 7 of CYP2C9 was detected in 1/40 (2.5%) patient. Our results reflect that genetic variations in COX-2, CYP2J2, and CYP2C9 genes may influence MS risk. |
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Supervisor |
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Dr. Hanan Saad Radah Althagafy |
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Thesis Type |
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Master Thesis |
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Publishing Year |
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1442 AH
2021 AD |
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Added Date |
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Monday, May 31, 2021 |
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Researchers
| أصايل غازي العتيبي | Alotaibi, Asayil Ghazi | Researcher | Master | |
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