Leptin reseptörü ve Hipoksi-İndüklenebilir Faktör-1alfa genlerindeki polimorfizmlerin OSAHS'la ilişkisi
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Dosyalar
Tarih
2018
Yazarlar
Dergi Başlığı
Dergi ISSN
Cilt Başlığı
Yayıncı
Necmettin Erbakan Üniversitesi Sağlık Bilimleri Enstitüsü
Erişim Hakkı
info:eu-repo/semantics/openAccess
Özet
Obstrüktif apne/hipoapne sendromu (OSAHS) obez bireylerde yaygın görülen çok odaklı bir
hastalıktır. Leptin hormonu yağ hücrelerinde üretilen, iştah ve enerji harcanmasının düzenlenmesinden
sorumlu olan bir sinyal faktörüdür. Leptinin spesifik reseptörü olan LEPR genellikle hipotalamusta
işlevseldir. OSAHS’da sık görülen bir durum kronik intermittent hipoksi (CIH) ‘dir. Hipoksiyle
İndüklenen Faktör-1α (HIF-1α), hipoksik koşullar altında oksijen homeostazının düzenlenmesine
yanıt sağlayan bir transkripsiyon faktörüdür.
Çalışmaya Konya popülasyonundan cinsiyeti erkek 154 hasta ve 39 sağlıklı bireyden oluşan
kontrol grubu dahil edilmiştir. Bütün hasta ve kontrol bireylerine polisomnografi testi uygulanmıştır.
Gruplar, genotip dağılımı; yaş, BMI (Body Mass İndex), boyun ve bel çevresi, AHI (Apne Hipoapne
İndeksi), Total Kolesterol, Trigliserit, HDL (High-density lipoprotein), LDL (Low-density
lipoprotein), Kan basıncı (Sistolik ve Diastolik), SpO2 (Oksijen saturasyonu) ve Epwort Uykululuk
skalası değişkenleri ile karşılaştırılmıştır. OSAHS’ın patofizyolojik sinyal yolaklarını etkileyip
etkilemediğini belirlemek için HIF-1α genindeki Pro582Ser polimorfizm ile LEPR genindeki
Lys109Arg ve Lys656Asn polimorfizmlerinin genotip dağılımları ARMS-PZR ve PZR-RFLP
moleküler tanı yöntemleri kullanılarak belirlenmiştir.
Tüm SNP’lerde hasta ve kontrol bireyleri arasında yaş, kilo, BMI, AHI, boyun çevresi, bel
çevresi, oksijen saturasyonu (p<0,001) ve sistolik kan basıncı, Epworth (p<0,05) anlamlı bulundu. Bu
parametrelerin değerleri OSAHS’lı hastalarda daha yüksekti ancak, oksijen saturasyonu
OSAHS’lılarda daha düşüktü. Pro582Ser ve Lys109Arg polimorfizminde hem hasta hemde kontrol
grubunda genotip dağılımları ve allel sıklıkları arasında parametrelere göre anlamlı bir farklılık
gözlenmedi. Yalnızca Lys109Arg polimorfizminde dominant modelde HDL ve LDL değerini anlamlı
bulundu (p<0,05), Lys656Asn polimorfizminde ise OSAHS’lı hasta grubunun kodominant ve
dominant modelinde kilo, BMI, bel ve boyun çevresi, sistolik ve diastolik kan basıncını anlamlı
bulundu. Sonuç olarak gerek LEPR gerekse HIF-1α geninde belirlenen diğer polimorfizmlerin
moleküler tarama yöntemleri kullanılarak yeteri kadar veri bulunmayan Türk populasyonunda
etkilerinin araştırılması uygun olacaktır.
Obstructive Sleep Apnea/Hypoapnea Syndrome is a multifactorial disease widely seen in obese individuals. Obesity and OSAHS have shared multi physiopathological mechanisms. Leptin hormone is a adipocyte-derived signaling factor that has an important role in metabolic control. Leptin is responsible for energy expenditure and reduction of food intake and Leptin’s specific receptor (LEPR) is generally functional in hypothalamus. Firstly, the aim of this study is to investigate the relation between OSAHS and Lys109Arg and Lys656Asn polymorphisms in LEPR. Chronic intermittent hypoxia (CIH) is a frequent feature of OSAHS. Cellular response to intermittent hypoxia and reoxygenation should provide insight into pathophysiological pathways in OSAHS. Hypoxia inducible factor-1α (HIF-1α) is a transcription factor that is responsible for the regulation of oxygen homeostasis under hypoxic conditions. The second aim of this study is to investigate the relation between OSAHS and Pro582Ser polymorphism in LEPR. Our study was included 154 patients and 39 healthy control individuals who were all male, from Konya populations. Diagnostic polysomnography was performed in all patients and control individuals. The results between both groups and distributions of genotyping were compared with data of ages, weight, BMI (Body Mass Index), neck and waist circumference, AHI (Apnea Hypoapnea Index), total cholesterol, triglyceride, HDL (High-density lipoprotein), LDL (Low-density lipoprotein), sistolic-diastolic blood pressure (SBP), SpO2 (saturation of oxygen) and Epworth Sleepiness Scale. The distribution of genotyping of Lys109Arg and Lys656Asn polymorphisms was determined with the method PCR-RFLP of a molecular diagnostic and HaeIII and BstU1 restriction enzyme was used, respectively. ARMS-PZR method was used for Pro582Ser polimorfizm. There were statistically significant difference between patients with OSAHS and control individulas in terms of weight, BMI, AHI, neck and waist circumference, SpO2 (P<0,001) and ages, sistolik blood pressure, Epworth characteristics (p<0,05). These data values was higher in OSAHS patiens but, SpO2 was lower. In LEPR polimorphisms any interaction was not determined between distributions of genotyping and allel frequencies. There were statistically significance differences HDL and LDL values in dominant models in Lys109Arg. OSAHS patients in dominant and co-dominant models in Lys656Asn polimorphism was statistically significant weight, BMI, neck and waist circumference, sistolic-diastolic blood pressure. By using molecular research methods of other polymorphisms in both leptin receptor and HIF-1α, it is necessary to search the effect of Leptin receptor and HIF-1α on OSAHS in Turkish population that has not enough data. It needs to widespread studies for determination of genetic basic on multifactorial patients like OSAHS.
Obstructive Sleep Apnea/Hypoapnea Syndrome is a multifactorial disease widely seen in obese individuals. Obesity and OSAHS have shared multi physiopathological mechanisms. Leptin hormone is a adipocyte-derived signaling factor that has an important role in metabolic control. Leptin is responsible for energy expenditure and reduction of food intake and Leptin’s specific receptor (LEPR) is generally functional in hypothalamus. Firstly, the aim of this study is to investigate the relation between OSAHS and Lys109Arg and Lys656Asn polymorphisms in LEPR. Chronic intermittent hypoxia (CIH) is a frequent feature of OSAHS. Cellular response to intermittent hypoxia and reoxygenation should provide insight into pathophysiological pathways in OSAHS. Hypoxia inducible factor-1α (HIF-1α) is a transcription factor that is responsible for the regulation of oxygen homeostasis under hypoxic conditions. The second aim of this study is to investigate the relation between OSAHS and Pro582Ser polymorphism in LEPR. Our study was included 154 patients and 39 healthy control individuals who were all male, from Konya populations. Diagnostic polysomnography was performed in all patients and control individuals. The results between both groups and distributions of genotyping were compared with data of ages, weight, BMI (Body Mass Index), neck and waist circumference, AHI (Apnea Hypoapnea Index), total cholesterol, triglyceride, HDL (High-density lipoprotein), LDL (Low-density lipoprotein), sistolic-diastolic blood pressure (SBP), SpO2 (saturation of oxygen) and Epworth Sleepiness Scale. The distribution of genotyping of Lys109Arg and Lys656Asn polymorphisms was determined with the method PCR-RFLP of a molecular diagnostic and HaeIII and BstU1 restriction enzyme was used, respectively. ARMS-PZR method was used for Pro582Ser polimorfizm. There were statistically significant difference between patients with OSAHS and control individulas in terms of weight, BMI, AHI, neck and waist circumference, SpO2 (P<0,001) and ages, sistolik blood pressure, Epworth characteristics (p<0,05). These data values was higher in OSAHS patiens but, SpO2 was lower. In LEPR polimorphisms any interaction was not determined between distributions of genotyping and allel frequencies. There were statistically significance differences HDL and LDL values in dominant models in Lys109Arg. OSAHS patients in dominant and co-dominant models in Lys656Asn polimorphism was statistically significant weight, BMI, neck and waist circumference, sistolic-diastolic blood pressure. By using molecular research methods of other polymorphisms in both leptin receptor and HIF-1α, it is necessary to search the effect of Leptin receptor and HIF-1α on OSAHS in Turkish population that has not enough data. It needs to widespread studies for determination of genetic basic on multifactorial patients like OSAHS.
Açıklama
Doktora Tezi
Anahtar Kelimeler
OSAHS, LEPR, HIF-1α, Polimorfizm, Lys109Arg, Lys656Asn, Pro582Ser, PZR-RFLP, ARMS
Kaynak
WoS Q Değeri
Scopus Q Değeri
Cilt
Sayı
Künye
Çetinkaya, S. (2018). Leptin reseptörü ve Hipoksi-İndüklenebilir Faktör-1alfa genlerindeki polimorfizmlerin OSAHS'la ilişkisi. (Yayımlanmamış doktora tezi). Necmettin Erbakan Üniversitesi, Sağlık Bilimleri Enstitüsü Tıbbi Biyoloji Anabilim Dalı, Konya.
