Rasmaizatul Akma ROSDİ, Nurfadhlina MUSA, Zalına ZAHARI, Zahrı KHAIRI, Mulham ALFATAMA, Boon Yin KHOO

Malezya'daki Malaylar Arasında İrritabl Bağırsak Sendromu (IBS) ile ilişkili Tek Nükleotid Polimorfizmlerinin Genotip ve Alel Frekansları

Amaç: Kronik veya tekrarlayan karın ağrısı veya rahatsızlığı ve bağırsak alışkanlıklarında değişiklik ile tanımlanan irritabl bağırsak sendromu (irritable bowel syndrome, IBS), en sık görülen fonksiyonel gastrointestinal bozukluktur. Çalışmalar, genlerdeki polimorfizmlerin, IBS'de altta yatan anahtar rollerden biri olduğunu kanıtlamıştır. Bu çalışmada, Malezya'nın ilişkisiz, sağlıklı Malaylarında, GNB3 (rs54443) ve SCN5A (rs8015124) genlerinden, IBS ile ilişkili tek nükleotid polimorfizminin (single nucleotide polymorphism, SNP) genotiplerinin ve alel frekanslarının araştırılması amaçlanmıştır. Gereç ve Yöntemler: Toplam 404 katılımcının genomik DNA'sı, yukarıda belirtilen SNP'leri belirlemek için yuvalanmış, multipleks ve alele özgü polimeraz zincir reaksiyonu (polymerase chain reaction, PCR) ile analiz edildi. PCR sonuçları, Sanger sıralama analizi ile doğrulandı. Bulgular: Malaylar, rs5443'te %56,3’e karşı %43,7 ile mutant (T) alellerinden biraz daha yüksek bir yabanıl (C) alel frekansına sahipti. Bununla birlikte, alellerin frekansları Malay kadınlar alt grubunda eşitti (C-%50, T-%50). rs1805124 için, Malayların sadece %18,6'sı mutant alel G'yi taşıyordu ve 10'dan az katılımcı homozigot mutant GG taşıyıcılarıydı. Aynı zamanda, çalışmadaki SNP Hardy-Weinberg dengesinden de sapmamıştı. Sonuç: İBS, kişinin yaşam kalitesini önemli ölçüde düşüren ve toplumlara ekonomik yük haline gelen yaygın bir gastrointestinal sorunudur. Mutant alellerin oldukça düşük olmasına rağmen, IBS ile ilişkili polimorfizmlerin, rs5443 ve rs1805124'ün Malaylarda yaygın olarak bulunduğu kaydedildi. rs5443 ve rs1805124 polimorfizmleri ile sendromun ilişkisini doğrulamak için yerel IBS hastaları üzerinde daha fazla araştırma yapılması önerilir.

Anahtar Kelimeler:

Genetik popülasyon, irritabl bağırsak sendromu, Malayca, rs5443, rs1805124

Genotype and Allele Frequencies of Irritable Bowel Syndrome (IBS)-associated Single Nucleotide Polymorphisms among Malays in Malaysia

Aim: Irritable bowel syndrome (IBS) defined by chronic or recurrent abdominal pain or discomfort and changes in bowel habits, is the most common functional gastrointestinal disorder. Studies proved that polymorphisms in the genes were one of the key roles in the underlying IBS. This study aimed to investigate the genotypes and allele frequencies of the IBS-associated single nucleotide polymorphism (SNP) from the genes GNB3 (rs54443) and SCN5A (rs8015124) in unrelated, healthy Malays of Malaysia. Material and Methods: The genomic DNA of 404 subjects was set to nested, multiplex, and allele-specific PCR to determine the aforementioned SNPs. The PCR results were validated through the Sanger sequencing analysis. Results: Malays possessed a slightly higher frequency of wild (C) than mutant (T) alleles in the rs5443 with 56.3 vs 43.7%. However, the frequencies of the alleles were equivalent in the subset of Malay females (C-50%, T-50%). For rs1805124, only 18.6% of Malays carried the mutant allele G with less than 10 subjects being homozygous mutant GG carriers. Concurrently, the Hardy-Weinberg equilibrium of the SNPs in the study was not deviated. Conclusion: IBS is a common gastrointestinal problem that has significantly reduced the life quality of oneself and become an economic burden to societies. Though the mutant alleles were rather low, the IBS-associated polymorphisms, rs5443 and rs1805124 were noted to be commonly present in the Malays. Further research on the local IBS patients is recommended to affirm the association of rs5443 and rs1805124 polymorphisms and the syndrome.

Keywords:

Genetic population, irritable bowel syndrome, Malay, rs5443, rs1805124,

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