Publication: Glukokortikoid reseptör polimorfizmleri ve metabolik sendrom arasındaki ilişki
Abstract
1. ÖZET Glukokortikoid Reseptör Polimorfizmleri ve Metabolik Sendrom Arasındaki İlişki Metabolik sendrom (MetS), insülin direnci ve tip 2 diyabet, abdominal obezite, dislipidemi, hipertansiyon veya mikroalbuminüri kriterlerinden en az ikisinin bir arada bulunması ile karakterize bir hastalıktır. Bozulmuş glukokortikoid hormon aktivitesi MetS’un etiyolojisine katkıda bulunmaktadır. Glukokortikoid reseptör (GR) gen polimorfizmleri ile bireyler arasında GC’lere duyarlılığın değiştiği bilinmektedir. Bu çalışmanın amacı, Türk toplumunda MetS’lu hastalarda glukokortikoid reseptör geni varyantlarının görülme sıklığını ve muhtemel ilişkisini araştırmaktır. Çalışmaya Dünya Sağlık Örgütü kriterlerine uygun MetS tanılı 70 hasta ve 180 sağlıklı birey alınmış, DNA izolasyonu ardından PZR-RFLP ile GR geninde BclI, N363S, ER22/ 23EK, TthllII polimorfizmleri için genotipleme yapılmıştır. Bcll kapsamında 32 (%45,7) doğal tip; 30 (%42,9) heterozigot; 8 (%11,4) polimorfik genotip saptanmıştır, kontrol grubunda oranlar sırasıyla 96 (%53,3), 77 (%42,8) ve 7 (%3,9)’dir. TthIIIl kapsamında hasta grubunda doğal tip 33 (%41,1), heterozigot 30 (%42,9) ve polimorfik genotip 7 (%10) olup, kontrol grubunda oranlar sırasıyla 70 (%38,9), 90 (%50) ve 20 (%11,1)’dir. Kontrol grubunda ER22/ 23EK için doğal tip allele rastlanmazken 9 (%5) heterozigot ve 171 (%95) polimorfik genotip saptanmıştır. Hasta grubunda, 1 (%1,4) doğal tip ve 69 (%98,6) homozigot polimorfik genotip görülmüştür. N363S dağılımı, polimorfik allel taşıyanların oranı hasta grubunda %1,5, kontrol grubunda %1,1 olarak saptanmıştır. ER22/ 23EK taşıyan olguların tümünün TthIIII de taşıdığı gözlenmiştir. GR geninin çalışılan polimorfizmleri arasında homozigot Bcll varyantı ve ER22/ 23EK ile TthlllI polimorfizmlerinin beraber bulunması MetS için iyi bir belirleyici olabileceği düşünülmektedir. Metabolik Sendrom, Glukokortikoid Reseptör Geni, Glukokortikoid Reseptör, Glukokortikoid, İnsülin Direnci. 2.
Relationship between Glucocorticoid Receptor Polymorphisms and Metabolic Syndrome The metabolic syndrome (MetS) is characterized by a cluster of metabolic factors including insulin resistance and type 2 diabetes, abdominal obesity, dislipidemia, hypertension and microalbuminuria. Impaired glucocorticoid hormon activity plays a role in the etiology of MetS. Glucocorticoid receptor polymorphisms seem to be associated with altered GC sensitivity among different population. This study evaluates the effects of GR gene polimorphisms on patients with MetS in Turkish population. 70 subjects with MetS and 180 healthy controls chosen according to WHO criteria were enrolled in the study. Standart protocols are carried out in DNA isolation followed by PCR and RFLP for GR gene polymorphisms (BclI, N363S, TthlllI ve ER22/ 23EK). Genotype distributions for BclI polymorphism in the patients were 32 (45,7%) wild type, 30 (42,9%) heterozygote and 8 (11,4%) homozygote mutant genotype. The results in control group was 96 (53,3%), 77 (42,8%) and 7 (3,9%), respectively. The distribution of TthlllI polymorphism in patients is 33 (47,1%) wild type, 30 (42,9%) heterozygote and 7 (10%) homozygote mutant, and 70 (38,9%), 90 (50%) and 20 (11,1%) respectively in controls. ER22/ 23EK polymorphism while no wild type allele was found, heterozygosity was 9 (%5) and mutant homozygote 171 (%95) in controls. In patinents homozygote wild type 1 (%1,4), homozygote mutant 69 (%98,6). The carriers of N363S variant allele was identified 1,5% in patient group and 1,1% in control group. However, all the ER22/ 23EK polymorphism coexisted with polymorphic variant of TthlllI (p=0.007). Presence of homozygote polymorphic variant of BclI polymorphism and coexistence with ER22/ 23EK and TthlllI polymorphism in the GR gene might be strong predictive markers for the MetS disease susceptibility. Key Word: Metabolic Syndrome, Glukokorticoid Receptor Gene, Glucocorticoid Receptor, Glucocorticoid, İnsülin resistance.
Relationship between Glucocorticoid Receptor Polymorphisms and Metabolic Syndrome The metabolic syndrome (MetS) is characterized by a cluster of metabolic factors including insulin resistance and type 2 diabetes, abdominal obesity, dislipidemia, hypertension and microalbuminuria. Impaired glucocorticoid hormon activity plays a role in the etiology of MetS. Glucocorticoid receptor polymorphisms seem to be associated with altered GC sensitivity among different population. This study evaluates the effects of GR gene polimorphisms on patients with MetS in Turkish population. 70 subjects with MetS and 180 healthy controls chosen according to WHO criteria were enrolled in the study. Standart protocols are carried out in DNA isolation followed by PCR and RFLP for GR gene polymorphisms (BclI, N363S, TthlllI ve ER22/ 23EK). Genotype distributions for BclI polymorphism in the patients were 32 (45,7%) wild type, 30 (42,9%) heterozygote and 8 (11,4%) homozygote mutant genotype. The results in control group was 96 (53,3%), 77 (42,8%) and 7 (3,9%), respectively. The distribution of TthlllI polymorphism in patients is 33 (47,1%) wild type, 30 (42,9%) heterozygote and 7 (10%) homozygote mutant, and 70 (38,9%), 90 (50%) and 20 (11,1%) respectively in controls. ER22/ 23EK polymorphism while no wild type allele was found, heterozygosity was 9 (%5) and mutant homozygote 171 (%95) in controls. In patinents homozygote wild type 1 (%1,4), homozygote mutant 69 (%98,6). The carriers of N363S variant allele was identified 1,5% in patient group and 1,1% in control group. However, all the ER22/ 23EK polymorphism coexisted with polymorphic variant of TthlllI (p=0.007). Presence of homozygote polymorphic variant of BclI polymorphism and coexistence with ER22/ 23EK and TthlllI polymorphism in the GR gene might be strong predictive markers for the MetS disease susceptibility. Key Word: Metabolic Syndrome, Glukokorticoid Receptor Gene, Glucocorticoid Receptor, Glucocorticoid, İnsülin resistance.