The Relationship Between the BCL1 Variant of the Glucocorticoid Receptor Gene and Non-Syndromic Microtia

Yıl 2020, Cilt: 3 Sayı: 3, 168 - 172, 05.11.2020

Ayşe Feyda Nursal , Kürşat Özdilli , Mehmet Bekerecioğlu , Berker Büyükgüral , Sacide Pehlivan

Öz

Objective: Microtia is defined as a congenitally defective external ear which has different degrees of severity from a simple isolated reduced size to complete loss of the ear. Normal fetal development is affected by the Glucocorticoids (GCs), which are critical for the maturation and development of different fetal tissues. The glucocorticoid receptors (GR) influence the GCs' actions. Therefore, we aimed to evaluate the association between the NR3C1 (encoding GR) gene BCL1 variant and its role in the development of non-syndromic microtia. Materials and Methods: Nineteen cases with microtia and forty healthy controls enrolled in the present study. We genotyped the NR3C1 BCL1 variant using the polymerase chain reaction (PCR) and PCR-restriction fragment length polymorphism (RFLP) method. The patients and controls were compared in terms of allele and genotype distribution using the χ2 test. Results: No statistical association was found between the NR3C1 BCL1 genotype distribution and microtia risk. However, the NR3C1 BCL1 variant G allele was lower in patients than in the healthy controls (p=0.034, OR:2.411, 95%Cl: 1.115-5.212) . In the current study, our results suggested that the subjects carrying the G allele in the NR3C1 gene BCL1 variant had a lower risk of microtia. Conclusion: Further studies are needed to determine whether this gene variant has a role in the risk of developing the disorder.

Anahtar Kelimeler

Microtia, DNA, glucocorticoid receptor, BCL1, variant

Sendromik Olmayan Microtia ve Glucocorticoid Receptor Genindeki BCL1 Variantının İlişkisi

Öz

Amaç: Microtia, basit izole küçük boyuttan tamamen kulak kaybına kadar farklı şiddet derecelerine sahip, kongenital kusurlu bir dış kulak olarak tanımlanır. Normal fetal gelişim, farklı fetal dokuların olgunlaşması ve gelişimi için kritik olan Glukokortikoidlerden (GK) etkilenir. Glukokortikoid reseptörleri (GR), GC’lerin fonksiyonlarını etkiler. Bu nedenle NR3C1 gen (GR kodlayan) BCL1 varyantı ile sendromik olmayan mikrotia gelişmesindeki rolü arasındaki ilişkiyi değerlendirmeyi amaçladık. Gereç ve Yöntem: Bu çalışmaya ondokuz mikrotia olgusu ve kırk sağlıklı kontrol dahil edildi. NR3C1 BCL1 varyantı polimeraz zincir reaksiyonu (PZR) ve sınırlayıcı parça uzunluk poliorfizmi (RFLP) yöntemini kullanarak genotipledik. Hastalar ve kontroller χ2 testi kullanılarak alel ve genotip dağılımı açısından karşılaştırıldı. Bulgular: NR3C1 BCL1 genotip dağılımı ve mikrotia arasında istatistiksel bir ilişki bulunmadı. Bununla birlikte, NR3C1 BCL1 varyant G aleli hastalarda sağlıklı kontrollere göre daha düşüktü (p=0.034, OR:2.411, 95%Cl: 1.115-5.212). Bu çalışmada, sonuçlarımız NR3C1 gen BCL1 varyantı G aleli taşıyan kişilerin daha düşük bir mikrotia riskine sahip olduğunu gösterdi. Sonuç: Bu gen varyantının, bozukluk riskinin gelişmesinde bir rolü olup olmadığını belirlemek için daha fazla çalışmaya ihtiyaç vardır.

Anahtar Kelimeler

Microtia, DNA, glukokortikoid reseptör, BCL1, varyant

Kaynakça

• 1. Alasti F, Van Camp G. Genetics of Microtia and Associated Syndromes. J Med Genet. 2009;46(6): 361-69 .
• 2. Luquetti DV, Heike CL, Hing AV, Cunningham ML, Cox TC. Microtia: Epidemiology & Genetics. Am J Med Genet A. 2012;158A(1): 124-39.
• 3. McEwen BS. Physiology and neurobiology of stress and adaptation: central role of the brain. Physiol Rev. 2007;87(3):873-904.
• 4. Korgun ET, Ozmen A, Unek G, Mendilcioglu I. The Effects of Glucocorticoids on Fetal and Placental Development. X Qian (Ed.), Glucocorticoids – New Recognition of Our Familiar Friend, InTech, Croatia 2012; 305-36.
• 5. El-Fayoumi R, Hagras M, Abozenadaha A, Bawazir W, Shinawi T. Association Between NR3C1 Gene Polymorphisms and Toxicity Induced by Glucocorticoids Therapy in Saudi Children with Acute Lymphoblastic Leukemia. Asian Pac J Cancer Prev. 2018; 19(5): 1415-23.
• 6. Fleury I, Beaulieu P, Primeau M, Labuda D, Sinnett D, Krajinovic M. Characterization of the BclI polymorphism in the glucocorticoid receptor gene. Clin Chem. 2003;49:1528-31.
• 7. Miller SA, Dykes DD, Polesky HF. A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acids Res. 1988;16:1215.
• 8. Aydeniz A, Sever T, Pehlivan S, Pehlivan M, Altındag O, Budeyri S, Gursoy S. Investigation of Glucocorticoid Receptor Gene Bcl-1 Polymorphism in Rheumatoid Arthritis. Turk J Rheumatol 2011;26(3):199-203.
• 9. Ruimin Qiao, Yuyong He, Bo Pan, Shijun Xiao, Xufei Zhang, Jing Li, Zhiyan Zhang, Yuan Hong, Understanding the molecular mechanisms of human microtia via a pig model of HOXA1 syndrom. Disease Models & Mechanisms 2015;8:611-22.
• 10. Gendron C, Schwentker A, van Aalst JA. Genetic Advances in the Understanding of Microtia. J Pediatr Genet. 2016; 5(4):189-97.
• 11. Bromer C, Marsit CJ, Armstrong DA, Padbury JF, Lester B. Genetic and epigenetic variation of the glucocorticoid receptor (NR3C1 ) in placenta and infant neurobehavior. Developmental Psychobiology 2013;55(7):673-83.
• 12. Timmermans S, Souffriau J, Libert C. A General Introduction to Glucocorticoid Biology. Front Immunol. 2019;10:1545.
• 13. Mangelsdorf DJ, Thummel C, Beato M, Herrlich P, Schütz G, Umesono K, Blumberg B, Kastner P, Mark M. The nuclear receptor superfamily: the second decade. Cell. 1995; 83:835-39.
• 14. Wust S, Federenko IS, van Rossum EF, Koper JW, Kumsta R, Entringer S, Hellhammer DH. A psychobiological perspective on genetic determinants of hypothalamus-pituitary-adrenal axis activity. Ann N Y Acad Sci. 2004;1032:52-62.
• 15. Srivastava N, Prakash J, Lakhan R, Agarwal CG, Pant DC, Mittal B. Influence of Bcl-1 Gene Polymorphism of Glucocorticoid Receptor Gene (NR3C1, rs41423247) on Blood Pressure, Glucose in Northern Indians. Indian J Clin Biochem. 2011;26(2):125-30.
• 16. van Rossum EF, Koper JW, van den Beld AW, Uitterlinden AG, Arp P, Ester W, et al. Identification of the BclI polymorphism in the glucocorticoid receptor gene: association with sensitivity to glucocorticoids in vivo and body mass index. Clin Endocrinol (Oxf). 2003;59(5):585-92.
• 17. Szappanos A, Patócs A, Töke J, Boyle B, Sereg M, Majnik J, Borgulya G, Varga I, Likó I, Rácz K, Tóth M. BclI polymorphism of the glucocorticoid receptor gene is associated with decreased bone mineral density in patients with endogenous hypercortisolism. Clin Endocrinol (Oxf). 2009;71(5):636-43.