TÜRK SAĞLIKLI BİREYLERDE CDKAL1 rs7754840 G>C POLİMORFİZMİNİN ALEL VE GENOTİP SIKLIKLARI: POPÜLASYON TEMELLİ BİR ÇALIŞMA

Öz

Amaç: CDKAL1 rs7754840 G>C polimorfizmi, kusurlu insülin salınımı ve tip 2 diyabet riskinin artmasıyla bağlantılıdır. Bu araştırmanın amacı, sağlıklı Türk bireylerde rs7754840 G>C polimorfizminin alel ve genotip sıklıklarını belirlemek ve bunları diğer popülasyonlarda gözlenen sıklıklarla karşılaştırmaktır. Bulgular ayrıca, diyabet riski ve tedavi yanıtı üzerindeki rolü hakkındaki önceki araştırmalara dayanarak tartışılmıştır.

Gereç ve Yöntem: CDKAL1 rs7754840 polimorfizmi, 112 sağlıklı Türk bireyden alınan DNA örneklerinde polimeraz zincir reaksiyonu ve restriksiyon fragman uzunluk polimorfizmi yöntemiyle incelendi. Alel ve genotip sıklıkları değerlendirildi ve farklı popülasyonlardan elde edilen verilerle istatistiksel olarak karşılaştırıldı.

Sonuç ve Tartışma: Genotip analizinde homozigot varyant için %7.1, heterozigot için %40.2 ve homozigot yabanıl tip için %52.7 sıklıkları belirlendi; bu da %27.2 (varyant) ve %72.8 (yabanıl tip) alel sıklıklarına karşılık geliyordu. CDKAL1 rs7754840 varyant alelinin sıklıkları, Amerikan, Finli olmayan Avrupalı, Güney Asyalı ve çoğu Doğu Asyalı popülasyonda belirlenen sıklıklarla tutarlıydı (p>0,05). Ancak, varyant alel sıklığı Afrika kökenli popülasyonlarda bildirilen sıklıktan önemli ölçüde farklıydı. Sonuç olarak, bu araştırma sağlıklı Türk bireylerinde CDKAL1 rs7754840 varyantının sıklığı hakkında güncel veriler sunmaktadır. Türk popülasyonu ile diğer bazı etnik gruplar arasında genotip ve alel frekanslarının önemli ölçüde farklı olduğu gözlemlendi. Bu bulguların genetik epidemiyoloji, farmakogenetik ve kişiselleştirilmiş tıp alanındaki gelecekteki araştırmalara katkı sağlayabilir.

Anahtar Kelimeler

• CDKAL1
• polimorfizm
• rs7754840
• Türk popülasyonu

Destekleyen Kurum

Yazarlar bu çalışma için herhangi bir finansal destek sağlanmadığını bildirmektedirler.

Etik Beyan

Çalışma için Mersin Üniversitesi Etik Kurulu'ndan onay alındı ​​(02 Eylül 2020, Referans Numarası: 2020/614). Bu çalışmada kullanılan DNA örnekleri, Mersin Üniversitesi Etik Kurulu tarafından daha önce onaylanan bir projeden elde edildi (22 Ekim 2015, Referans Numarası: 2015/317). Kan alımı sırasında tüm gönüllülerden yazılı onam alındı.

ALLELE AND GENOTYPE FREQUENCIES OF THE CDKAL1 rs7754840 G>C POLYMORPHISM IN TURKISH HEALTHY INDIVIDUALS: A POPULATION-BASED STUDY

Öz

Objective: The CDKAL1 rs7754840 G>C polymorphism is link to defective insulin release and an elevated risk of type 2 diabetes mellitus. The objective of the current research was to identify the frequencies of alleles and genotypes for the rs7754840 G>C polymorphism in healthy Turkish individuals and to contrast them with those observed in other populations. The findings were also discussed based on previous research about its role in diabetes risk and treatment response.

Material and Method: The CDKAL1 rs7754840 polymorphism was examined in DNA samples obtained from 112 healthy Turkish subjects through polymerase chain reaction and restriction fragment length polymorphism process. Allele and genotype frequencies were assessed and statistically compared with data from diverse populations.

Result and Discussion: Genotype analysis revealed frequencies of 7.1% for homozygous variant, 40.2% for heterozygous, and 52.7% for homozygous witd-type, corresponding to allele frequencies of 27.2% (variant) and 72.8% (wild-type). The frequencies of the CDKAL1 rs7754840 variant allele were consistent with those determined in American, non-Finnish European, South Asian, and most East Asian populations (p>0.05). However, the variant allele frequency differed significantly from that reported in populations of Black ancestry. In conclusion, the present research offers current data on the frequency of the CDKAL1 rs7754840 variant in healthy Turkish individuals. Genotype and allele frequencies were observed to be significantly distinct between the Turkish population and several other ethnic groups. These findings may contribute to future research in genetic epidemiology, pharmacogenetics, and personalized medicine.

Anahtar Kelimeler

• CDKAL1
• polymorphism
• rs7754840
• Turkish population

Destekleyen Kurum

The authors report that no financial support was provided for this study.

Etik Beyan

Approval for the study was received from the Mersin University Ethics Committee (02 September 2020, Reference Number: 2020/614). The DNA samples utilized in this study were derived from a previous project endorsed by the Mersin University Ethics Committee (22 October 2015, Reference Number: 2015/317). Written informed consent was received from all volunteers during blood collection.

Kaynakça

1. 1. The Diabetes Atlas website. (2025). https://diabetesatlas.org/data-by-location/country/trkiye/. Accessed date: 08.05.2025.
2. 2. Mansoori, Y., Daraei, A., Naghizadeh, M.M., et al. (2015). Significance of a common variant in the CDKAL1 gene with susceptibility to type 2 diabetes mellitus in Iranian population. Advanced Biomedical Research, 4, 45. [CrossRef]
3. 3. Hu, F.B. (2011). Globalization of diabetes: The role of diet, lifestyle, and genes. Diabetes Care, 34(6), 1249-1257. [CrossRef]
4. 4. McCarthy, M.I. (2010). Genomics, type 2 diabetes, and obesity. The New England Journal of Medicine, 363, 2339-2350. [CrossRef]
5. 5. Soltani, G., Hatefi, Z., Salehi, A.R., et al. (2018). Pharmacogenomics of sulfonylureas response in relation to rs7754840 polymorphisms in cyclin-dependent kinase 5 regulatory subunit-associated protein 1-like (CDKAL1) gene in iranian type 2 diabetes patients. Advanced Biomedical Research, 7, 96. [CrossRef]
6. 6. Mahdizade, A.H., Bahreiny, S.S., Bastani, M.N., et al. (2024). The influence of CDKAL1 (rs7754840) gene polymorphism on susceptibility to gestational diabetes mellitus in pregnant women: a systematic review and meta‑analysis. International Journal of Diabetes in Developing Countries, 44 (Suppl 1), 3-12. [CrossRef]
7. 7. Darwish, R., Abdel-Hamid, E., Gohar, N., et al. (2020). Single nucleotide polymorphisms in CDKAL1 gene are not associated with risk of type 2 diabetes mellitus in a group of Egyptian population. Biomedical and Pharmacology Journal, 13(2), 529-535. [CrossRef]
8. 8. Steinthorsdottir, V., Thorleifsson, G., Reynisdottir, I., et al. (2007). A variant in CDKAL1 influences insulin response and risk of type 2 diabetes. Nature Genetics, 39(6), 770-775.

9. 9. Sim, X., Ong, R.T.H., Suo, C., et al. (2011). Transferability of type 2 diabetes implicated loci in multi-ethnic cohorts from Southeast Asia. PLoS Genetics, 7(4), e1001363. [CrossRef]
10. 10. Helvaci, Ö., Korucu, B., Yeter, H.H., et al. (2023). TCF7L2 (rs7903146) But Not CDKAL1 (rs7754840) Gene polymorphisms increase the risk of new-onset diabetes after kidney transplant. Experimental and Clinical Transplantation, 21(11), 872-878. [CrossRef]
11. 11. Tuerxunyiming, M., Mohemaiti, P., Wufuer, H., et al. (2015). Association of rs7754840 G/C polymorphisms in CDKAL1 with type 2 diabetes: A meta-analysis of 70141 subjects. International Journal of Clinical and Experimental Medicine, 8(10), 17392-17405.
12. 12. Stancáková, A., Pihlajamäki, J., Kuusisto, J., et al. EUGENE2 Consortium. (2008). Single-nucleotide polymorphism rs7754840 of CDKAL1 is associated with impaired insulin secretion in nondiabetic offspring of type 2 diabetic subjects and in a large sample of men with normal glucose tolerance. The Journal of Clinical Endocrinology & Metabolism, 93(5), 1924-1930. [CrossRef]
13. 13. Osada, U.N., Sunagawa, H., Terauchi, Y., et al. (2016). Common susceptibility gene for type 2 diabetes is associated with drug response to a DPP-4 inhibitor: Pharmacogenomic cohort in Okinawa Japan. PLoS One, 11(5), e0154821. [CrossRef]
14. 14. Qin, M., Chao, L., Liu, S. (2025). Comparative efficacy and safety of sitagliptin or gliclazide combined with metformin in treatment-naive patients with type 2 diabetes: A single-center, prospective, randomized, controlled, noninferiority study with genetic polymorphism analysis. Medicine (Baltimore). 2025; 104(2): e41061. [CrossRef]
15. 15. Arikoglu, H., Erkoc-Kaya, D., Ipekci, S.H., et al. (2021). Type 2 diabetes is associated with the MTNR1B gene, a genetic bridge between circadian rhythm and glucose metabolism, in a Turkish population. Molecular Biology Reports, 48(5), 4181-4189. [CrossRef]
16. 16. Auton, A., Brooks, L.D., Durbin, R.M., et al. (2015). A global reference for human genetic variation. Nature, 526(7571), 68-74. [CrossRef]
17. 17. Ensembl Genome Browser website. (2025). https://www.ensembl.org. Accessed date: 08.05.2025.
18. 18. Naser, F.H., Fadheel, H.K., Hussain, M.K., et al. (2021). Association of CDKAL1 gene polymorphisms with type 2 diabetes mellitus in a sample of Iraqi population. Gene Reports, 25, 101371. [CrossRef]
19. 19. Uckun Sahinogullari, Z. (2020). Cytochrome P450 2A13 3375C>T gene polymorphism in a Turkish population. İstanbul Journal of Pharmacy, 50(3), 181-187. [CrossRef]