Toll-like receptor 10 gene polymorphism and risk of multiple sclerosis among Iraqi patients

Background Toll-like receptors (TLRs) are a family of 10 pattern recognition receptors (TLR1–TLR10) involved in the regulation of inflammatory and immune responses besides their role in the pathogenesis of autoimmune diseases including multiple sclerosis (MS). TLR10 is the least studied TLR in MS, a...

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Veröffentlicht in:Egyptian Journal of Medical Human Genetics 2022-05, Vol.23 (1), p.88-10, Article 88
Hauptverfasser: Atiyah, Noor S., Fadhil, Hula Y., Ad’hiah, Ali H.
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Ad’hiah, Ali H.
description Background Toll-like receptors (TLRs) are a family of 10 pattern recognition receptors (TLR1–TLR10) involved in the regulation of inflammatory and immune responses besides their role in the pathogenesis of autoimmune diseases including multiple sclerosis (MS). TLR10 is the least studied TLR in MS, and data for single nucleotide polymorphisms (SNPs) of the TLR10 gene are limited. Therefore, a case–control study was performed on 85 patients with relapsing–remitting MS and 86 healthy controls (HC) to explore SNPs in the promoter region of TLR10 gene. A 927-bp region was amplified, and Sanger sequencing identified 10 SNPs with a minor allele frequency ≥ 10% (rs200395112 T/A, rs201802754 A/T, rs201228097 T/A, rs113588825 G/A, rs10004195 T/A, rs10034903 C/G, rs10012016 G/A/C, rs10012017 G/T, rs33994884 T/Deletion [Del] and rs28393318 A/G). Results Del allele and T/Del genotype of rs33994884, as well as AG genotype of rs28393318, showed significantly lower frequencies in MS patients compared to HC. Allele and genotype frequencies of the 10 SNPs showed no significant differences between MS patients classified according to the Expanded Disability Status Scale. Haplotype analysis revealed that haplotype A-T-A-G-A-G-G-T-A showed a significantly increased frequency in MS patients compared to HC (odds ratio [OR] = 9.70; 95% confidence interval [CI] = 1.28–73.31; corrected probability [ pc ] = 0.03), while frequency of A-T-A-G-T-C-A-T-G haplotype was significantly decreased (OR = 0.10; 95% CI = 0.01–0.85; pc  = 0.05). Conclusions The study indicated that two SNPs may influence susceptibility to MS (rs33994884 and rs28393318), but haplotype analysis of TLR10 gene SNPs was more informative.
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TLR10 is the least studied TLR in MS, and data for single nucleotide polymorphisms (SNPs) of the TLR10 gene are limited. Therefore, a case–control study was performed on 85 patients with relapsing–remitting MS and 86 healthy controls (HC) to explore SNPs in the promoter region of TLR10 gene. A 927-bp region was amplified, and Sanger sequencing identified 10 SNPs with a minor allele frequency ≥ 10% (rs200395112 T/A, rs201802754 A/T, rs201228097 T/A, rs113588825 G/A, rs10004195 T/A, rs10034903 C/G, rs10012016 G/A/C, rs10012017 G/T, rs33994884 T/Deletion [Del] and rs28393318 A/G). Results Del allele and T/Del genotype of rs33994884, as well as AG genotype of rs28393318, showed significantly lower frequencies in MS patients compared to HC. Allele and genotype frequencies of the 10 SNPs showed no significant differences between MS patients classified according to the Expanded Disability Status Scale. Haplotype analysis revealed that haplotype A-T-A-G-A-G-G-T-A showed a significantly increased frequency in MS patients compared to HC (odds ratio [OR] = 9.70; 95% confidence interval [CI] = 1.28–73.31; corrected probability [ pc ] = 0.03), while frequency of A-T-A-G-T-C-A-T-G haplotype was significantly decreased (OR = 0.10; 95% CI = 0.01–0.85; pc  = 0.05). Conclusions The study indicated that two SNPs may influence susceptibility to MS (rs33994884 and rs28393318), but haplotype analysis of TLR10 gene SNPs was more informative.</description><identifier>ISSN: 2090-2441</identifier><identifier>ISSN: 1110-8630</identifier><identifier>EISSN: 2090-2441</identifier><identifier>DOI: 10.1186/s43042-022-00301-0</identifier><language>eng</language><publisher>Berlin/Heidelberg: Springer Berlin Heidelberg</publisher><subject>Alleles ; Autoimmune diseases ; B cells ; DNA sequencing ; Ethylenediaminetetraacetic acid ; Expanded disability status scale ; Gene frequency ; Gene polymorphism ; Genes ; Genetic aspects ; Genotype &amp; phenotype ; Haplotype ; Haplotypes ; Immune response ; Inflammation ; Medical research ; Medicine ; Medicine &amp; Public Health ; Medicine, Experimental ; Multiple sclerosis ; Nucleotide sequencing ; Pattern recognition receptors ; Relapsing–remitting multiple sclerosis ; Single nucleotide polymorphism ; Single nucleotide polymorphisms ; TLR1 protein ; Toll-like receptor 10 ; Toll-like receptors</subject><ispartof>Egyptian Journal of Medical Human Genetics, 2022-05, Vol.23 (1), p.88-10, Article 88</ispartof><rights>The Author(s) 2022</rights><rights>COPYRIGHT 2022 Springer</rights><rights>The Author(s) 2022. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c377t-5f99e2d974ca2b0a559dc6bc5037fbc659267033eb9949e5d4b7ed9079e13b3e3</cites><orcidid>0000-0002-2445-2242</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,860,27901,27902</link.rule.ids></links><search><creatorcontrib>Atiyah, Noor S.</creatorcontrib><creatorcontrib>Fadhil, Hula Y.</creatorcontrib><creatorcontrib>Ad’hiah, Ali H.</creatorcontrib><title>Toll-like receptor 10 gene polymorphism and risk of multiple sclerosis among Iraqi patients</title><title>Egyptian Journal of Medical Human Genetics</title><addtitle>Egypt J Med Hum Genet</addtitle><description>Background Toll-like receptors (TLRs) are a family of 10 pattern recognition receptors (TLR1–TLR10) involved in the regulation of inflammatory and immune responses besides their role in the pathogenesis of autoimmune diseases including multiple sclerosis (MS). TLR10 is the least studied TLR in MS, and data for single nucleotide polymorphisms (SNPs) of the TLR10 gene are limited. Therefore, a case–control study was performed on 85 patients with relapsing–remitting MS and 86 healthy controls (HC) to explore SNPs in the promoter region of TLR10 gene. A 927-bp region was amplified, and Sanger sequencing identified 10 SNPs with a minor allele frequency ≥ 10% (rs200395112 T/A, rs201802754 A/T, rs201228097 T/A, rs113588825 G/A, rs10004195 T/A, rs10034903 C/G, rs10012016 G/A/C, rs10012017 G/T, rs33994884 T/Deletion [Del] and rs28393318 A/G). Results Del allele and T/Del genotype of rs33994884, as well as AG genotype of rs28393318, showed significantly lower frequencies in MS patients compared to HC. Allele and genotype frequencies of the 10 SNPs showed no significant differences between MS patients classified according to the Expanded Disability Status Scale. Haplotype analysis revealed that haplotype A-T-A-G-A-G-G-T-A showed a significantly increased frequency in MS patients compared to HC (odds ratio [OR] = 9.70; 95% confidence interval [CI] = 1.28–73.31; corrected probability [ pc ] = 0.03), while frequency of A-T-A-G-T-C-A-T-G haplotype was significantly decreased (OR = 0.10; 95% CI = 0.01–0.85; pc  = 0.05). Conclusions The study indicated that two SNPs may influence susceptibility to MS (rs33994884 and rs28393318), but haplotype analysis of TLR10 gene SNPs was more informative.</description><subject>Alleles</subject><subject>Autoimmune diseases</subject><subject>B cells</subject><subject>DNA sequencing</subject><subject>Ethylenediaminetetraacetic acid</subject><subject>Expanded disability status scale</subject><subject>Gene frequency</subject><subject>Gene polymorphism</subject><subject>Genes</subject><subject>Genetic aspects</subject><subject>Genotype &amp; phenotype</subject><subject>Haplotype</subject><subject>Haplotypes</subject><subject>Immune response</subject><subject>Inflammation</subject><subject>Medical research</subject><subject>Medicine</subject><subject>Medicine &amp; Public Health</subject><subject>Medicine, Experimental</subject><subject>Multiple sclerosis</subject><subject>Nucleotide sequencing</subject><subject>Pattern recognition receptors</subject><subject>Relapsing–remitting multiple sclerosis</subject><subject>Single nucleotide polymorphism</subject><subject>Single nucleotide polymorphisms</subject><subject>TLR1 protein</subject><subject>Toll-like receptor 10</subject><subject>Toll-like receptors</subject><issn>2090-2441</issn><issn>1110-8630</issn><issn>2090-2441</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2022</creationdate><recordtype>article</recordtype><sourceid>C6C</sourceid><sourceid>BENPR</sourceid><sourceid>DOA</sourceid><recordid>eNp9UU1P3TAQjCoqFWj_QE-Weg5df8X2EaECT0LiQk89WI6zSf1I4mDnHfj3GIJKK6HKa621mhmNd6rqK4UzSnXzPQsOgtXAygUOtIYP1TEDAzUTgh799f5UneS8B2gkV-K4-nUXx7Eewz2ShB6XNSZCgQw4I1ni-DjFtPwOeSJu7kgK-Z7EnkyHcQ3LiCT7EVPMIRM3xXkgu-QeAlncGnBe8-fqY-_GjF9e-2n18_LH3cV1fXN7tbs4v6k9V2qtZW8Mss4o4R1rwUlpOt-0XgJXfesbaVijgHNsjREGZSdahZ0BZZDyliM_rXabbhfd3i4pTC492uiCfRnENFiX1lC8Wq690Y5qpTsQ0HPnKTQKpRYNM6KVRevbprWk-HDAvNp9PKS52LesONHMaEPfUIMromHu45qcn0L29lwBK0WNLqizd1DldDgFH2fsQ5n_Q2AbwZel5oT9n89QsM852y1nW3K2LzlbKCS-kXIBzwOmN8f_YT0BcM6oJg</recordid><startdate>20220505</startdate><enddate>20220505</enddate><creator>Atiyah, Noor S.</creator><creator>Fadhil, Hula Y.</creator><creator>Ad’hiah, Ali H.</creator><general>Springer Berlin Heidelberg</general><general>Springer</general><general>Springer Nature B.V</general><general>SpringerOpen</general><scope>C6C</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>CWDGH</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M7P</scope><scope>PHGZM</scope><scope>PHGZT</scope><scope>PIMPY</scope><scope>PKEHL</scope><scope>PQEST</scope><scope>PQGLB</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>DOA</scope><orcidid>https://orcid.org/0000-0002-2445-2242</orcidid></search><sort><creationdate>20220505</creationdate><title>Toll-like receptor 10 gene polymorphism and risk of multiple sclerosis among Iraqi patients</title><author>Atiyah, Noor S. ; 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TLR10 is the least studied TLR in MS, and data for single nucleotide polymorphisms (SNPs) of the TLR10 gene are limited. Therefore, a case–control study was performed on 85 patients with relapsing–remitting MS and 86 healthy controls (HC) to explore SNPs in the promoter region of TLR10 gene. A 927-bp region was amplified, and Sanger sequencing identified 10 SNPs with a minor allele frequency ≥ 10% (rs200395112 T/A, rs201802754 A/T, rs201228097 T/A, rs113588825 G/A, rs10004195 T/A, rs10034903 C/G, rs10012016 G/A/C, rs10012017 G/T, rs33994884 T/Deletion [Del] and rs28393318 A/G). Results Del allele and T/Del genotype of rs33994884, as well as AG genotype of rs28393318, showed significantly lower frequencies in MS patients compared to HC. Allele and genotype frequencies of the 10 SNPs showed no significant differences between MS patients classified according to the Expanded Disability Status Scale. Haplotype analysis revealed that haplotype A-T-A-G-A-G-G-T-A showed a significantly increased frequency in MS patients compared to HC (odds ratio [OR] = 9.70; 95% confidence interval [CI] = 1.28–73.31; corrected probability [ pc ] = 0.03), while frequency of A-T-A-G-T-C-A-T-G haplotype was significantly decreased (OR = 0.10; 95% CI = 0.01–0.85; pc  = 0.05). Conclusions The study indicated that two SNPs may influence susceptibility to MS (rs33994884 and rs28393318), but haplotype analysis of TLR10 gene SNPs was more informative.</abstract><cop>Berlin/Heidelberg</cop><pub>Springer Berlin Heidelberg</pub><doi>10.1186/s43042-022-00301-0</doi><tpages>10</tpages><orcidid>https://orcid.org/0000-0002-2445-2242</orcidid><oa>free_for_read</oa></addata></record>
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subjects Alleles
Autoimmune diseases
B cells
DNA sequencing
Ethylenediaminetetraacetic acid
Expanded disability status scale
Gene frequency
Gene polymorphism
Genes
Genetic aspects
Genotype & phenotype
Haplotype
Haplotypes
Immune response
Inflammation
Medical research
Medicine
Medicine & Public Health
Medicine, Experimental
Multiple sclerosis
Nucleotide sequencing
Pattern recognition receptors
Relapsing–remitting multiple sclerosis
Single nucleotide polymorphism
Single nucleotide polymorphisms
TLR1 protein
Toll-like receptor 10
Toll-like receptors
title Toll-like receptor 10 gene polymorphism and risk of multiple sclerosis among Iraqi patients
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