Huda AHMED, Deniz MIHÇIOĞLU, Filiz ÖZBAŞ GERÇEKER, Başar AKSOY

KIR2DL4 gen polimorfizmlerinin obezite ile ilişkisi

Amaç: Obezite dünyanın pek çok yerinde görülmekte olup halk sağlığının temel sorunlarından biri haline gelmiştir. Obezite, genetik, davranışsal, çevresel, fizyolojik, sosyal ve kültürel değişkenlerin sebep olduğu enerji dengesizliği ve gereksiz yağ birikimi sonucu oluşur. Ülkemizde de diğer ülkelerde olduğu gibi obezite görülme sıklığı gün geçtikçe artmaktadır. Obezitenin, kanser, kalp-damar hastalıkları, diyabet, hipertansiyon gibi birçok riskli hastalığın gelişmesini kolaylaştırdığı gösterilmiştir. Obeziteye eşlik eden bir diğer önemli hastalık grubu da immün sistem hastalıklarıdır. Obez bireylerdeki inflamasyon değişiklikleri ve immün hücre fonksiyonları, obezitenin patofizyolojik etkilerinin oluşmasında önemli bir role sahiptir. Obezite, multifaktöryel ve kompleks bir hastalıktır. Doğal öldürücü hücreler (NK) sitotoksik lenfositlerdir ve doğal bağışıklık sisteminin önemli bir parçasıdır. Doğal öldürücü hücre immunglobulin benzeri reseptörler (KIR) hem NK hücrelerinde eksprese olan transmembran glikoproteinleridir hem de T hücrelerinin alt grubudur. KIR2DL4, hücresel konum, sinyalleşme, ligandların özgüllüğü ve protein işlevi açısından diğer KIR geni aile üyelerine göre atipiktir. Çalışmada, KIR2DL4 polimorfizmleri ile obezite arasındaki ilişkiyi araştırmak amaçlanmıştır. Yöntem: Çalışmaya, 50 obez (BKI≥30) ve 50 obez olmayan (BKI≤30) birey katılmıştır. Kan örnekleri toplanarak, DNA izolasyonları yapılmış PCR reaksiyonu ile KIR2DL4 geninin ilgili bölgeleri çoğaltılıp uygun enzimle kesildikten sonra genotip sayımı yapılmıştır. Allel ve genotip frekansları direk sayım yöntemi ile hesaplanmış ve gruplardaki genotip dağılımları ki-kare analizi ile karşılaştırılmıştır. Bulgular: Obezite ve rs649216 ve rs660773 polimorfizmleri arasında istatistiksel olarak anlamlı bir ilişki bulunmamıştır (p>0.05). Fakat, KIR2DL4 rs660437– 9769 C > A polimorfizminin genotip sıklıklarının hasta ve kontrol grubunda karşılaştırılması sonucunda istatistiksel olarak anlamlı bir fark gözlenmiştir (p=0.004). CC genotip sıklığı obez grupta (%44) kontrol grubuna (%24) göre daha yüksek bulunmuştur. Sonuç: rs660437 C allel frekansı obez grupta anlamlı olarak daha yüksek bulunmuştur, bu nedenle hastalığın gelişimi için bir risk faktörü olabilir (p=0.004).

Association of KIR2DL4 gene polymorphisms with obesity

Objective: Obesity is seen at many parts of the world and has become one of the main issues of public health. Obesity is the consequence of genetic, behavioral, environmental, physiological, social and cultural variables resulting in energy imbalance and encouraging unnecessary accumulation of fat. In our country, as in other countries, the incidence of obesity is increasing day by day. It has been shown that obesity contributes to the development of many risky diseases such as cancer, cardiovascular diseases, diabetes, hypertension. Another important disease group accompanying obesity is immune system diseases. Inflammation changes and immune cell functions in obese individuals play an important role in the pathophysiological effects of obesity. Obesity is a multifactorial and complex disease. Natural killer (NK) cell is cytotoxic lymphocytes, which is essential element of innate immune system. The human killer cell immunoglobulin like receptors (KIR) which is a class of transmembrane glycoproteins expressed on NK cell as well as a subgroup of T cell. KIR2DL4 is atypical KIR which varies by other family members in terms of cellular location, signaling, specificity of ligands, as well as protein function. The aim of the study was to investigate the relationship between KIR2DL4 polymorphisms and obesity. Methods: 50 obese (BMI≥30) and 50 non-obese (BMI≤30) individuals participated in the study. After collecting blood samples, DNA isolations and PCR reaction, the relevant regions of the KIR2DL4 gene were amplified and digest with the suitable enzyme. Allele and genotype frequencies were calculated by direct counting and genotype distributions in the groups were compared by chi-square analysis. Results: No statistically significant association was found between obesity and rs649216, rs660773 polymorphisms (p>0.05). However, a significant difference was determined as a result of the comparison of genotype frequencies of KIR2DL4 rs660437– 9769 C > A polymorphism between obese and control group (p=0.004). CC genotype frequency was found to be higher in obese group (44%) than in control group (24%). Conclusion: rs660437 C allel frequency was significantly higher in obese group, so it might be a risk factor for the development of the disease (p=0.004).

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