Fibromiyalji sendromu ile transient reseptör potansiyel melastatin 8 (TRPM8) kanalı gen ekspresyonu ve polimorfizmi arasındaki ilişkinin incelenmesi
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2021
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info:eu-repo/semantics/openAccess
Özet
Amaç: Fibromiyalji sendromu (FMS) genellikle yorgunluk, kognitif disfonsiyon, psikiyatrik semptomlar ve çoklu somatik semptomların eşlik ettiği kronik yaygın kas-iskelet sistemi ağrısı nedenidir. Etiyolojisi ve patofizyolojik mekanizmaları tam olarak bilinmemektedir. Bu çalışmanın amacı TRPM8 tek gen polimorfizmleri (rs10166942, rs11562975) ve gen ekspresyon düzeyi ile FMS'nin varlığı, semptom şiddeti ve farklı klinik özelliklerinin arasındaki ilişkinin incelenmesidir. Materyal ve Metod: Çalışmaya 2016 ACR tanı kriterlerine göre FMS tanısı almış 60 kişiden oluşan hasta grubu ve 40 kişiden oluşan kontrol grubu olmak üzere toplam 100 kişi dahil edildi. Tüm katılımcıların demografik özellikleri kaydedildi. Her iki gruba da Görsel Analog Ölçek, Yorgunluk Şiddet Ölçeği (YŞÖ), Fibromiyalji Etki Anketi (FEA), Beck Depresyon Ölçeği (BDÖ), Pittsburgh Uyku Kalitesi İndeksi (PUKİ), Mini Mental Test (MMT) uygulandı. Katılımcıların periferik kan örneklerinden total RNA izolasyonu yapılarak RT-PCR yöntemi ile TRPM8 gen ekspresyonu belirlendi. Polimorfizm bölgelerindeki değişen alleller, allele özgü nükleotidlerle mutasyon belirleme teknigi (ARMS-PCR) kullanılarak belirlendi. Elde edilen sonuçlar IBM SPSS Statistics 20 programı kullanılarak analiz edildi. Bulgular: Elde edilen sonuçlara göre hasta grubundaki bireylerin gen ekspresyon düzeyleri kontrol grubuna oranla istatistiksel olarak anlamlı düzeyde yüksek idi (hasta grubu ort=9.33±2.41, kontrol grubu ort=6.29±2.76, p<0.001). Kontrol grubuna göre hasta grubunda TRPM8 mRNA düzeylerinde 8,24 kat artış (kat değişimi=8,24) gözlemlendi. Tüm katılımcılar değerlendirildiğinde yaygın ağrı düzeyi ve semptom şiddeti, VAS, YŞÖ, FEA, BDÖ, PUKİ skorları ile gen ekspresyon düzeyleri arasında pozitif yönlü korelasyon vardı. MMT puanları ile gen ekspresyon vi düzeyleri arasında negatif yönlü korelasyon mevcuttu (p<0.001). Hasta grubundaki kadınlarla kontrol grubundaki kadınlar değerlendirildiğinde rs10166942 ve rs11562975 polimorfizim dağılımları arasında anlamlı fark saptandı (p<0.05). Hasta grubundaki kadınların kontrol grubundaki kadınlara göre rs10166942 T allel dağılımı anlamlı olarak yüksekti. Sonuç: TRPM8 geni, FMS gelişimi ve semptom şiddeti ile ilişkilendirilebilecek genetik faktörlerden biri olabilir. Çalışmamız sonuçlarına göre FMS hastalarında TRPM8 gen ekspresyon düzeyi artmaktadır. Gen ekspresyonu düzeyi arttıkça katılımcıların fibromiyalji ile ilişkili semptomları kötüleşmektedir. Ayrıca FMS yatkınlığı ile allel ve genotip sıklığı açısından rs10166942 ve rs11562975 polimorfizimleri arasında anlamlı bir bağlantı olabileceği saptanmıştır. Bu konuda daha net verilere ulaşabilmek için TRPM8 ile FMS arasındaki ilişkiyi ortaya koyan daha büyük örneklem boyutuna sahip ve diğer etnik gruplarda yapılan araştırmalara ihtiyaç vardır. Anahtar Kelimeler: Fibromiyalji sendromu, etyopatogenez, TRPM8, gen ekspresyon, polimorfizm
Purpose: Fibromyalgia syndrome (FMS) is a common cause of chronic widespread musculoskeletal pain, often accompanied by fatigue, cognitive dysfunction, psychiatric symptoms, and multiple somatic symptoms. Its etiology and pathophysiological mechanisms are not fully known. The aim of this study is to examine the relationship between TRPM8 single gene polymorphisms (rs10166942, rs11562975) and gene expression level and the presence of FMS, symptom severity and different clinical features. Materials and Methods: A total of 100 people were included in the study, according to the 2016 ACR diagnostic criteria, the patient group consisting of 60 people diagnosed with FMS and the control group consisting of 40 people without FMS diagnosis. Demographic characteristics of all participants were recorded. Visual Analog Scale (VAS), Fatigue Severity Scale (FSS), Fibromyalgia Impact Questionnaire (FIQ), Beck Depression Scale (BDS), Pittsburgh Sleep Quality Index (PSQI), Mini-mental state examination (MMSE) were implemented to both groups. Total RNA was isolated from peripheral blood samples of the participants and TRPM8 gene expression was determined by RT-PCR method. Altered alleles in polymorphism regions were determined using the amplification refractory mutation system (ARMS-PCR). The results obtained were analyzed using the IBM SPSS Statistics 20 program. Results: According to the results obtained, the gene expression levels of the individuals in the patient group were statistically significantly higher than the control group (patient group mean=9.33±2.41, control group mean=6.29±2.76, p<0.001). An 8.24 fold increase (fold change=8.24) was observed in TRPM8 mRNA levels in the viii patient group compared to the control group. When all participants were evaluated, a positive correlation was seen between widespread pain level and symptom severity, VAS, FSS, FIQ, BDS, PUKI scores and gene expression levels. Apart from this, negative correlation was observed between MMT scores and gene expression levels (p<0.001). When the women in the patient group and the women in the control group were evaluated, a significant difference was found between rs10166942 and rs11562975 polymorphism distributions (p<0.05). The rs10166942 T allele distribution of the women in the patient group was significantly higher than the women in the control group. Conclusion: TRPM8 gene may be one of the genetic factors that can be associated with FMS development and symptom severity. According to the results of our study, TRPM8 gene expression level is increased in FMS patients. As the level of gene expression increased, participants fibromyalgia-related symptoms worsened. In addition, a significant correlation was found between FMS susceptibility and polymorphisms of rs10166942 and rs11562975 in terms of allele and genotype frequency. In order to reach clear data on this subject, studies with larger sample sizes and conducted in other ethnic groups revealing the relationship between TRPM8 and FMS are needed. Keywords: Fibromyalgia syndrome, etiopathogenesis, TRPM8, gene expression, polymorphism
Purpose: Fibromyalgia syndrome (FMS) is a common cause of chronic widespread musculoskeletal pain, often accompanied by fatigue, cognitive dysfunction, psychiatric symptoms, and multiple somatic symptoms. Its etiology and pathophysiological mechanisms are not fully known. The aim of this study is to examine the relationship between TRPM8 single gene polymorphisms (rs10166942, rs11562975) and gene expression level and the presence of FMS, symptom severity and different clinical features. Materials and Methods: A total of 100 people were included in the study, according to the 2016 ACR diagnostic criteria, the patient group consisting of 60 people diagnosed with FMS and the control group consisting of 40 people without FMS diagnosis. Demographic characteristics of all participants were recorded. Visual Analog Scale (VAS), Fatigue Severity Scale (FSS), Fibromyalgia Impact Questionnaire (FIQ), Beck Depression Scale (BDS), Pittsburgh Sleep Quality Index (PSQI), Mini-mental state examination (MMSE) were implemented to both groups. Total RNA was isolated from peripheral blood samples of the participants and TRPM8 gene expression was determined by RT-PCR method. Altered alleles in polymorphism regions were determined using the amplification refractory mutation system (ARMS-PCR). The results obtained were analyzed using the IBM SPSS Statistics 20 program. Results: According to the results obtained, the gene expression levels of the individuals in the patient group were statistically significantly higher than the control group (patient group mean=9.33±2.41, control group mean=6.29±2.76, p<0.001). An 8.24 fold increase (fold change=8.24) was observed in TRPM8 mRNA levels in the viii patient group compared to the control group. When all participants were evaluated, a positive correlation was seen between widespread pain level and symptom severity, VAS, FSS, FIQ, BDS, PUKI scores and gene expression levels. Apart from this, negative correlation was observed between MMT scores and gene expression levels (p<0.001). When the women in the patient group and the women in the control group were evaluated, a significant difference was found between rs10166942 and rs11562975 polymorphism distributions (p<0.05). The rs10166942 T allele distribution of the women in the patient group was significantly higher than the women in the control group. Conclusion: TRPM8 gene may be one of the genetic factors that can be associated with FMS development and symptom severity. According to the results of our study, TRPM8 gene expression level is increased in FMS patients. As the level of gene expression increased, participants fibromyalgia-related symptoms worsened. In addition, a significant correlation was found between FMS susceptibility and polymorphisms of rs10166942 and rs11562975 in terms of allele and genotype frequency. In order to reach clear data on this subject, studies with larger sample sizes and conducted in other ethnic groups revealing the relationship between TRPM8 and FMS are needed. Keywords: Fibromyalgia syndrome, etiopathogenesis, TRPM8, gene expression, polymorphism
Açıklama
Anahtar Kelimeler
Ağrı = Pain ; Etyopatogenez = Etiopathogenesis ; Fibromiyalji = Fibromyalgia ; Kas-iskelet hastalıkları = Musculoskeletal diseases
