İrritabl barsak sendromu (İBS) hastalarında brain-derived nörotrofik faktör (BDNF) düzeyi ve val66met polimorfizmi'nin tanısal değeri
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Dosyalar
Tarih
2020
Yazarlar
Dergi Başlığı
Dergi ISSN
Cilt Başlığı
Yayıncı
Düzce Üniversitesi
Erişim Hakkı
info:eu-repo/semantics/openAccess
Özet
Giriş ve Amaç: İrritabl barsak sendromu (İBS); karın ağrısı, abdominal rahatsızlık hissi, dışkılamanın formundaki ve sıklığındaki değişiklikler ile karakterize fonksiyonel bir barsak hastalığıdır. Etiyolojisi tam olarak bilinmemekle birlikte; psikolojik faktörler, beslenme alışkanlıkları ve barsak florasındaki değişiklikler gibi birçok faktörün sebep olduğu düşünülmektedir. Beyin-barsak aksı gastrointestinal yol (enterik sinir sistemi) ve beyin (merkezi sinir sistemi) arasında otonomik nöral, nöroimmün ve nöroendokrin yolakları kullanan çift yönlü bir bağlantı sistemi olarak tanımlanabilir. Bu sebeple barsak fonksiyonları bozulduğunda, bu bozukluğun sebebi beyin-barsak aksındaki merkezi sinir sisteminden gelen modulatör girdilerinden de kaynaklanabilir. Nörotrofinler; nöronal bakım, farklılaşma ve sağkalımın düzenlenmesi için oldukça önemli bir büyüme faktörleri ailesidir. Bunlar arasında beyin kaynaklı nörotrofik faktörün (Brain Derived Neurotrophic Factor, BDNF) disregülasyonunun nörodejeneratif hastalıklara karşı yatkınlığı arttırdığı bilinmektedir. BDNF, enterik sinir sistemi nöronları, intestinal mukoza epiteli, interstisyel aralık gibi intestinal traktusun farklı bölgelerinde oldukça yaygın bir şekilde dağılım gösterir. BNDF'nin barsak motilitesi üzerindeki fizyolojik etkilerini araştıran birçok çalışma mevcuttur. BDNF'nin pro-bölgesi içindeki 66 pozisyonunda valin (Val)' den metionine (Met) bir aminoasit değişimi (rs6265) fonksiyonel bir tek nükleotid polimorfizmine (SNP) sebep olur. Bu çalışmamızda İBS tanısı ile BNDF polimorfizminin ve serum BDNF düzeylerinin ilişkisini inceledik. Hastalar ve Metod: Düzce Üniversitesi Araştırma ve Uygulama Hastanesi İç Hastalıkları ve Gastroenteroloji polikliniklerine Ocak 2019- Eylül 2019 tarihleri arasında başvuran ve Roma IV kriterlerine göre İBS tanısı alan 60 hasta ve 40 sağlıklı birey gönüllülük esasına dayanılarak belirlendi. Hastaların serum örneklerinde BDNF düzeyleri insan BDNF monoklonal antikorları ile kaplanmış 96 kuyucuklu ELISA plakalarında, ticari satın alınan "Human Free BDNF Quantikine ELISA" test kitiyle (R&D Systems, Inc., Minneapolis, MN, USA) üreticinin çalışma protokolüne uygun olarak kantitatif düzeyde analiz edilmiştir. Ayrıca BDNF genotiplendirmesi tam kan örneklerinden DNA ekstraksiyonu ve sonrasında PCR-RLFP analizi ile yapıldı. BDNF analizi ELISA testi ve BDNF genotiplendirilmesi Karabük Üniversitesi Tıp Fakültesi Tıbbi Biyoloji ABD laboratuvarında çalışılmıştır. Bulgular: Hasta ve kontrol grubu karşılaştırıldığında ortalama BDNF düzeyleri arasında anlamlı farklılık saptandı. Ortalama BDNF düzeyi hasta grubunda istatistiksel olarak anlamlı düşük bulundu (p=0,019). Serum BDNF düzeyleri hasta grubunda ortalama 781,888 pg/mL (128,48-1501,6), kontrol grubunda ise 988,715 pg/mL (66,1-1948,8) olarak saptandı. İBS alt grup analizi yapıldığında da İBS-İ alt grubunda ortalama BDNF düzeyinde anlamlı düşüş saptandı. Psikiyatrik hastalık öyküsü, psikiyatrik ilaç kullanımı, sigara kullanımı için ortalama BDNF düzeyleri arasında anlamlı farklılık saptanmadı(p>0,05). Hasta ve kontrol grubu arasında Val ve Met allel frekansı değerlendirildi. Hasta grubunda Met allel frekansı % 17 iken kontrol grubunda % 12,5 olarak bulundu. Hasta ve kontrol grubunun genotipleri ve allel frekansları arasında anlamlı fark saptanmadı (p=0,499). Hastaların BDNF düzeyleri ve genotipleri arasında da anlamlı ilişki saptanmadı (p>0,05). Sonuç: Yaptığımız bu çalışmanın sonucunda temel olarak İBS'li hastalarda kontrol grubuna göre serum BDNF düzeyini daha düşük saptadık. Ancak hasta ve kontrol grubunda genotip açısından anlamlı fark görmedik. Ayrıca olguların genotipleri ile serum BDNF düzeyleri arasında da anlamlı bir ilişki olmadığını gördük. Bu durum BDNF geninin dinamik fonksiyonel regülasyon göstermesi sonucu farklı doku ve patolojilerde çeşitli ekspresyon paternine sahip olmasından kaynaklanıyor olabilir. Bu nedenle çalışmanın daha geniş hasta grubunda yapılması ve dolayısı ile Met allel sıklığının arttırılması istatistiksel olarak daha doğru sonuçlar elde edilmesini sağlayabilir. Çalışmamızın, bu konuda yapılacak daha geniş ve kontrollü çalışmalara ışık tutacağını umuyoruz.
Introduction: Irritable bowel syndrome (IBS) is a functional bowel disease characterized by abdominal discomfort, changes in the form and frequency of defecation. Although its etiology is not fully known, it is thought to be caused by many factors such as psychological factors, nutritional habits and changes in intestinal flora. The brain-bowel axis can be defined as a bidirectional connecting system that uses autonomic neural, neuroimmune, and neuroendocrine pathways between the gastrointestinal tract (enteric nervous system) and the brain (central nervous system). Therefore, when bowel function is impaired, this may also be caused by modulator inputs from the central nervous system in the brain-bowel axis. Neurotrophins are a quite important family of growth factors for the regulation of neuronal care, differentiation, and survival. Among these, dysregulation of brain-derived neurotrophic factor (BDNF) is known to increase susceptibility to neurodegenerative diseases. BDNF is widely distributed in different regions of the intestinal tractus such as enteric nervous system neurons, intestinal mucosa epithelium, interstitial space. There are many studies investigating the physiological effects of BNDF on intestinal motility. An aminoacid exchange (rs6265) from valine (Val) to methionine (Met) at position 66 within the pro-region of BDNF causes a functional single nucleotide polymorphism (SNP). Within the scope of this project, the relationship between IBS and BNDF polymorphism and serum BDNF levels were examined. Patients and Methods: 60 patients and 40 healthy individuals who were admitted to the Düzce University Research and Practice Hospital Internal Diseases and Gatroenterology outpatient clinics between January 2019 and September 2019 and diagnosed with IBS according to ROME 4 criteria were determined on a voluntary basis. In serum samples of patients, BDNF levels are in the 96-well ELISA plates coated with human BDNF monoclonal antibodies to the manufacturer's study protocol with the commercially purchased "Human Free BDNF Quantikine ELISA" test kit (R&D Systems, Inc., Minneapolis, MN, USA). It was appropriately analyzed at the quantitative level. In addition, BDNF genotyping was performed by DNA extraction from whole blood samples and subsequently by PCR-RLFP analysis. BDNF ELISA test and BDNF genotyping were studied in Karabuk University Faculty of Medicine Department of Medical Biology. Results: Mean serum BDNF levels were found as 781,888 pg / mL (128,48-1501,6) in the patient group and 988,715 pg / mL (66,1-1948,8) in the control group. Mean BDNF levels were significantly lower in the patient group (p=0.019) when compared to healthy controls. When the IBS subgroup analysis was performed, a significant decrease was found in the mean BDNF level in the IBS-I subgroup. There were no significant differences between the mean levels of BDNF for psychiatric history of disease, psychiayric drug use or smoking (p>0.05). Val and Met allele frequencies were evaluated between the patient and control groups. There was no significant difference between the genotypes and allele frequencies of the patient and control groups (p = 0.499). Met allele frequency was found to be 17% in the patient group and 12,5% in the control group. There was no significant association between BDNF levels and genotypes of the patients (p>0,05). Conclusion: As a result of our study, we found that serum BDNF level was lower in patients with IBS compared to the control group. However, there was no significant difference in genotype in the patient and control groups. We also found that there was no significant association between BDNF gene polymorphism and serum BDNF levels. This may be due to the fact that the BDNF gene has dynamic functional regulation and has various expression patterns in different tissues and pathologies. Therefore, the study should be conducted in a wider group of patients and therefore increasing the frequency of Met alleles may provide statistically more accurate results. We hope that our study will shed light on the wider and controlled work to be done on this issue.
Introduction: Irritable bowel syndrome (IBS) is a functional bowel disease characterized by abdominal discomfort, changes in the form and frequency of defecation. Although its etiology is not fully known, it is thought to be caused by many factors such as psychological factors, nutritional habits and changes in intestinal flora. The brain-bowel axis can be defined as a bidirectional connecting system that uses autonomic neural, neuroimmune, and neuroendocrine pathways between the gastrointestinal tract (enteric nervous system) and the brain (central nervous system). Therefore, when bowel function is impaired, this may also be caused by modulator inputs from the central nervous system in the brain-bowel axis. Neurotrophins are a quite important family of growth factors for the regulation of neuronal care, differentiation, and survival. Among these, dysregulation of brain-derived neurotrophic factor (BDNF) is known to increase susceptibility to neurodegenerative diseases. BDNF is widely distributed in different regions of the intestinal tractus such as enteric nervous system neurons, intestinal mucosa epithelium, interstitial space. There are many studies investigating the physiological effects of BNDF on intestinal motility. An aminoacid exchange (rs6265) from valine (Val) to methionine (Met) at position 66 within the pro-region of BDNF causes a functional single nucleotide polymorphism (SNP). Within the scope of this project, the relationship between IBS and BNDF polymorphism and serum BDNF levels were examined. Patients and Methods: 60 patients and 40 healthy individuals who were admitted to the Düzce University Research and Practice Hospital Internal Diseases and Gatroenterology outpatient clinics between January 2019 and September 2019 and diagnosed with IBS according to ROME 4 criteria were determined on a voluntary basis. In serum samples of patients, BDNF levels are in the 96-well ELISA plates coated with human BDNF monoclonal antibodies to the manufacturer's study protocol with the commercially purchased "Human Free BDNF Quantikine ELISA" test kit (R&D Systems, Inc., Minneapolis, MN, USA). It was appropriately analyzed at the quantitative level. In addition, BDNF genotyping was performed by DNA extraction from whole blood samples and subsequently by PCR-RLFP analysis. BDNF ELISA test and BDNF genotyping were studied in Karabuk University Faculty of Medicine Department of Medical Biology. Results: Mean serum BDNF levels were found as 781,888 pg / mL (128,48-1501,6) in the patient group and 988,715 pg / mL (66,1-1948,8) in the control group. Mean BDNF levels were significantly lower in the patient group (p=0.019) when compared to healthy controls. When the IBS subgroup analysis was performed, a significant decrease was found in the mean BDNF level in the IBS-I subgroup. There were no significant differences between the mean levels of BDNF for psychiatric history of disease, psychiayric drug use or smoking (p>0.05). Val and Met allele frequencies were evaluated between the patient and control groups. There was no significant difference between the genotypes and allele frequencies of the patient and control groups (p = 0.499). Met allele frequency was found to be 17% in the patient group and 12,5% in the control group. There was no significant association between BDNF levels and genotypes of the patients (p>0,05). Conclusion: As a result of our study, we found that serum BDNF level was lower in patients with IBS compared to the control group. However, there was no significant difference in genotype in the patient and control groups. We also found that there was no significant association between BDNF gene polymorphism and serum BDNF levels. This may be due to the fact that the BDNF gene has dynamic functional regulation and has various expression patterns in different tissues and pathologies. Therefore, the study should be conducted in a wider group of patients and therefore increasing the frequency of Met alleles may provide statistically more accurate results. We hope that our study will shed light on the wider and controlled work to be done on this issue.
Açıklama
YÖK Tez No: 622231
Anahtar Kelimeler
Gastroenteroloji, Gastroenterology
