Document Details
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Document Type |
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Thesis |
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Document Title |
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ASSOCIATION OF CYTOCHROME P450 GENETIC POLYMORPHISMS AND LEVEL OF STEROIDS IN MULTIPLE SCLEROSIS PATIENTS علاقة تعدد الأشكال الوراثية للسيتوكروم ب 450 بمستوى الإستيرويد لدى مرضى 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 an inflammatory demyelinating disease and the most common cause of neurological disability in young adults. The pathology of MS is still not completely understood. Genetic and environmental factors contribute to the etiology of MS. Several studies have suggested that steroid hormones play a role in the inflammatory process, damage, and repair mechanisms in MS. Mitochondrial cytochrome P450 side-chain cleavage enzyme (P450scc, CYP11A1) is the initiating enzyme of steroidogenesis. Steroidogenic acute regulatory protein (StAR) facilitates the movement of cholesterol into the inner mitochondrial membrane where P450scc cleaves the cholesterol side chain, converting cholesterol to pregnenolone, the precursor of steroids. This suggests that genetic alterations of steroidogenic enzymes could be correlated with an increased risk of developing MS. Therefore, we aimed to investigate the association between genetic polymorphisms of CYP11A1 and StAR genes, and levels of steroids in MS patients in the Saudi population. A case-control study was conducted on 40 MS cases and 20 controls. Genotyping was performed by polymerase chain reaction (PCR) and Sanger sequencing. In this study, there was a significant decrease in the level of progesterone in female and male patients (p = 0.01 and p < 0.001, respectively) compared to female and male controls. A significant increase in level of FSH in female and male patients (p = 0.05) compared to controls. There was a significant decrease in estradiol levels in male patients (p < 0.001) compared to male controls. Analysis of promoter region of the CYP11A1 gene revealed five different alleles [4-, 6-, 7- 8-, and 9-] (tttta) repeat polymorphisms in MS patients. The most frequent allele observed was six repeats (29.6%) in females and (38.5%) in males. A significant decrease of FSH level (p = 0.05) and a significant increase of cortisol level (p < 0.05) in female MS patients with the (tttta)4 allele compared to patients with the (tttta)6 allele. A total of 8 genetic variants were detected in the MS patients and healthy individuals including 4 novel variants. In the promoter region of the CYP11A1, rs79975126 and SNP G/C in chromosome position (15:74368301) were detected. In exon 2 of CYP11A1, two variants were detected rs1484215 and rs145866066. In the StAR gene at exon 5, three synonymous variants were detected (Glycine 201=), (Glutamate 211=), and (Glutamine 191=). In exon 7 of StAR, one synonymous variant rs757414809 was detected. A significant association between GG and GA genotypes of (rs1484215) variant in exon 2 of CYP11A1 and triglyceride levels was detected. The GG and GA genotypes of (8: 38145980) variant in exon 5 of StAR gene were associated with triglyceride (p = 0.03) and glucose (p = 0.05) levels. In conclusion, the changes in steroid hormones, lipid profile, and glucose levels may be associated with the risk of MS. Genetic variants in the CYP11A1 gene and StAR gene maybe influence MS risk. The (tttta)6 allele of CYP11A1 may be linked to MS in the Saudi population. |
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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
| سهام أحمد الشاردي | Al-Shardy, Siham Ahmed | Researcher | Master | |
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