Detection of mutations in NOD2/CARD15 gene in Arab patients with Crohn's disease
Background: Mutations in NOD2/CARD15 gene have been linked to an increased risk of Crohn's disease (CD). The objective of this study is to determine NOD2/CARD15 gene mutations, and their association with the risk of CD in Arabs in Kuwait. Methods: Four NOD2 gene mutations, including Pro268Ser (...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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Wolters Kluwer Medknow Publications
2021-01-01
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| Series: | The Saudi Journal of Gastroenterology |
| Subjects: | |
| Online Access: | http://www.saudijgastro.com/article.asp?issn=1319-3767;year=2021;volume=27;issue=4;spage=240;epage=248;aulast=Siddique |
| _version_ | 1819147254954459136 |
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| author | Iqbal Siddique Abu S Mustafa Islam Khan Ali H Ziyab Munira Altarrah Riyas Sulaiman Numeer Kadungothayil Faraz Shaheed |
| author_facet | Iqbal Siddique Abu S Mustafa Islam Khan Ali H Ziyab Munira Altarrah Riyas Sulaiman Numeer Kadungothayil Faraz Shaheed |
| author_sort | Iqbal Siddique |
| collection | DOAJ |
| description | Background: Mutations in NOD2/CARD15 gene have been linked to an increased risk of Crohn's disease (CD). The objective of this study is to determine NOD2/CARD15 gene mutations, and their association with the risk of CD in Arabs in Kuwait.
Methods: Four NOD2 gene mutations, including Pro268Ser (SNP5), Arg702Trp (SNP8), Gly908Arg (SNP12), and Leu1007FsinsC (SNP13) were examined in Arab CD patients (n = 103) and control subjects (n = 100). The genomic DNA was isolated and used in polymerase chain reaction (PCR) with four sets of specific primers. The PCR-amplified DNA fragments were sequenced and analyzed for the NOD2 mutations. Logistic regression was used to estimate the adjusted odds ratios (aOR) and 95% confidence intervals (CI).
Results: Of the four genotyped variants, the Arg702Trp (SNP8) and Leu1007FsinsC (SNP13) variants were not informative in our study sample due to minor allele frequency of <1%. The Pro268Ser (SNP5) mutation was detected in 17 (16.5%) CD patients and 32 (32.0%) controls. The Gly908Arg (SNP12) mutation was observed in 24 (23.3%) patients and 10 (10.0%) controls. In the dominant genetic risk model (i.e. carrying at least one minor allele), CD patients compared to controls were less likely to carry either the “CT” or “TT” genotype of variant Pro268Ser (SNP5; aOR = 0.43, 95% CI: 0.22–0.84). In contrast, CD patients compared to controls were more likely to carry the homozygous for the minor allele or the heterozygous genotypes of variant Gly908Arg (SNP12; aOR = 2.67, 95% CI: 1.19–5.97).
Conclusions: In this Arab population, carrying at least one copy of the minor allele of Gly908Arg (SNP12) mutation in NOD2 gene was associated with increased susceptibility to CD, while having the heterozygous or homozygous for the minor allele genotype of the Pro268Ser (SNP5) mutation provided protection against CD. Mutations in Arg702Trp (SNP8) and Leu1007FsinsC (SNP13) were not detected in this sample of the Arab population in Kuwait. |
| first_indexed | 2024-12-22T13:26:54Z |
| format | Article |
| id | doaj.art-124083acc8c24ac69a7ac8c19f700a6b |
| institution | Directory Open Access Journal |
| issn | 1319-3767 1998-4049 |
| language | English |
| last_indexed | 2024-12-22T13:26:54Z |
| publishDate | 2021-01-01 |
| publisher | Wolters Kluwer Medknow Publications |
| record_format | Article |
| series | The Saudi Journal of Gastroenterology |
| spelling | doaj.art-124083acc8c24ac69a7ac8c19f700a6b2022-12-21T18:24:16ZengWolters Kluwer Medknow PublicationsThe Saudi Journal of Gastroenterology1319-37671998-40492021-01-0127424024810.4103/sjg.sjg_582_20Detection of mutations in NOD2/CARD15 gene in Arab patients with Crohn's diseaseIqbal SiddiqueAbu S MustafaIslam KhanAli H ZiyabMunira AltarrahRiyas SulaimanNumeer KadungothayilFaraz ShaheedBackground: Mutations in NOD2/CARD15 gene have been linked to an increased risk of Crohn's disease (CD). The objective of this study is to determine NOD2/CARD15 gene mutations, and their association with the risk of CD in Arabs in Kuwait. Methods: Four NOD2 gene mutations, including Pro268Ser (SNP5), Arg702Trp (SNP8), Gly908Arg (SNP12), and Leu1007FsinsC (SNP13) were examined in Arab CD patients (n = 103) and control subjects (n = 100). The genomic DNA was isolated and used in polymerase chain reaction (PCR) with four sets of specific primers. The PCR-amplified DNA fragments were sequenced and analyzed for the NOD2 mutations. Logistic regression was used to estimate the adjusted odds ratios (aOR) and 95% confidence intervals (CI). Results: Of the four genotyped variants, the Arg702Trp (SNP8) and Leu1007FsinsC (SNP13) variants were not informative in our study sample due to minor allele frequency of <1%. The Pro268Ser (SNP5) mutation was detected in 17 (16.5%) CD patients and 32 (32.0%) controls. The Gly908Arg (SNP12) mutation was observed in 24 (23.3%) patients and 10 (10.0%) controls. In the dominant genetic risk model (i.e. carrying at least one minor allele), CD patients compared to controls were less likely to carry either the “CT” or “TT” genotype of variant Pro268Ser (SNP5; aOR = 0.43, 95% CI: 0.22–0.84). In contrast, CD patients compared to controls were more likely to carry the homozygous for the minor allele or the heterozygous genotypes of variant Gly908Arg (SNP12; aOR = 2.67, 95% CI: 1.19–5.97). Conclusions: In this Arab population, carrying at least one copy of the minor allele of Gly908Arg (SNP12) mutation in NOD2 gene was associated with increased susceptibility to CD, while having the heterozygous or homozygous for the minor allele genotype of the Pro268Ser (SNP5) mutation provided protection against CD. Mutations in Arg702Trp (SNP8) and Leu1007FsinsC (SNP13) were not detected in this sample of the Arab population in Kuwait.http://www.saudijgastro.com/article.asp?issn=1319-3767;year=2021;volume=27;issue=4;spage=240;epage=248;aulast=Siddiquearabcard15crohn's diseasegenetickuwaitnod2 |
| spellingShingle | Iqbal Siddique Abu S Mustafa Islam Khan Ali H Ziyab Munira Altarrah Riyas Sulaiman Numeer Kadungothayil Faraz Shaheed Detection of mutations in NOD2/CARD15 gene in Arab patients with Crohn's disease The Saudi Journal of Gastroenterology arab card15 crohn's disease genetic kuwait nod2 |
| title | Detection of mutations in NOD2/CARD15 gene in Arab patients with Crohn's disease |
| title_full | Detection of mutations in NOD2/CARD15 gene in Arab patients with Crohn's disease |
| title_fullStr | Detection of mutations in NOD2/CARD15 gene in Arab patients with Crohn's disease |
| title_full_unstemmed | Detection of mutations in NOD2/CARD15 gene in Arab patients with Crohn's disease |
| title_short | Detection of mutations in NOD2/CARD15 gene in Arab patients with Crohn's disease |
| title_sort | detection of mutations in nod2 card15 gene in arab patients with crohn s disease |
| topic | arab card15 crohn's disease genetic kuwait nod2 |
| url | http://www.saudijgastro.com/article.asp?issn=1319-3767;year=2021;volume=27;issue=4;spage=240;epage=248;aulast=Siddique |
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