Defb1-KO Mouse

Defb1, encoding human Beta Defensin-1 (hBD-1), is a gene involved in the innate immune system, which is the first line of defense against pathogens. hBD-1 is an antimicrobial peptide participating in epithelial defence of various tissues, also present in saliva. Genetic variations in Defb1 may influence gene expression and protein production, potentially modifying innate immune system responses and oral health [8].

Multiple studies have explored associations between Defb1 polymorphisms and various diseases. A meta-analysis showed that the Defb1-G1654A polymorphism may be a genetic susceptibility factor for periodontitis [1]. Another meta-analysis indicated that the Defb1 rs11362 polymorphism may not have an important effect on the risk of chronic periodontitis [2]. In a Zambian population, Defb1 polymorphisms were significantly associated with a decreased risk of HIV-1 infection acquisition [3]. In an Egyptian population, different Defb1 gene polymorphisms may modify the risk of vitiligo development, disease extent, and response to NB-UVB phototherapy [4]. No association was found between studied Defb1 polymorphisms and tuberculosis in a Northeastern Brazilian population, though the sample size may have affected the result [5]. The rs11362 A/G polymorphism of Defb1 was associated with the risk of developing coronary artery disease (CAD), with the AA genotype linked to low β-defensin-1 mRNA expression in heart tissues [6]. In Chinese 12-year-old children, carriers of the Defb1 rs11362 T allele had a higher risk of dental caries [7]. In Italian children, there was no significant correlation between most Defb1 polymorphisms and recurrent tonsillitis susceptibility, except for an increased risk in patients carrying rare haplotypes [9].

In conclusion, Defb1 is crucial for innate immune responses, especially in epithelial defence. Studies on Defb1 polymorphisms have revealed their associations with diseases like periodontitis, HIV-1 MTCT, vitiligo, CAD, dental caries, and recurrent tonsillitis. These findings contribute to understanding the role of Defb1 in disease susceptibility and progression, providing insights for potential disease prevention and treatment strategies related to innate immune-associated disorders.

References:

1. Zhong, Shichun, Wang, Caijun, Gao, Renhui, Shu, Shuang, Shu, Chengjun. . Association between DEFB1 polymorphisms and periodontitis: a meta-analysis. In Die Pharmazie, 74, 390-396. doi:10.1691/ph.2019.9459. https://pubmed.ncbi.nlm.nih.gov/31288894/

2. Shao, Jun, Zhang, Miao, Wu, Lan, Jin, Ying-Hui, Zeng, Xian-Tao. 2019. DEFB1 rs11362 Polymorphism and Risk of Chronic Periodontitis: A Meta-Analysis of Unadjusted and Adjusted Data. In Frontiers in genetics, 10, 179. doi:10.3389/fgene.2019.00179. https://pubmed.ncbi.nlm.nih.gov/30915104/

3. Zupin, Luisa, Polesello, Vania, Segat, Ludovica, Kuhn, Louise, Crovella, Sergio. 2018. DEFB1 polymorphisms and HIV-1 mother-to-child transmission in Zambian population. In The journal of maternal-fetal & neonatal medicine : the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians, 32, 2805-2811. doi:10.1080/14767058.2018.1449206. https://pubmed.ncbi.nlm.nih.gov/29506422/

4. Salem, Rehab Mohammed, Abdelrahman, Amira Mohamed Noureldin, Abd El-Kareem, Heba Mohamed, Seif, Marwa. 2021. DEFB1 gene polymorphisms modify vitiligo extent and response to NB-UVB phototherapy. In Dermatologic therapy, 34, e14921. doi:10.1111/dth.14921. https://pubmed.ncbi.nlm.nih.gov/33647170/

5. Celerino da Silva, Ronaldo, da Cruz, Heidi Lacerda Alves, Brandão, Lucas André Cavalcanti, Segat, Ludovica, Crovella, Sergio. 2016. DEFB1 gene polymorphisms and tuberculosis in a Northeastern Brazilian population. In Brazilian journal of microbiology : [publication of the Brazilian Society for Microbiology], 47, 389-93. doi:10.1016/j.bjm.2015.09.001. https://pubmed.ncbi.nlm.nih.gov/26991287/

6. Vargas-Alarcón, Gilberto, Pérez-Méndez, Óscar, Martínez-Ríos, Marco Antonio, Ramírez-Bello, Julián, Fragoso, José Manuel. 2024. The DEFB1 gene rs11362 A/G genetic variant is associated with risk of developing CAD: a case-control study. In Acta cardiologica, 79, 730-736. doi:10.1080/00015385.2024.2375487. https://pubmed.ncbi.nlm.nih.gov/38973431/

7. Ma, Fei, He, Haoyu, Chen, Shaoyong, Liu, Qiulin, Zeng, Xiaojuan. 2023. Associations of PART1 and DEFB1 polymorphisms with Dental Caries in twelve-year-old children in Southern China: a cross-sectional study. In BMC pediatrics, 23, 6. doi:10.1186/s12887-022-03678-4. https://pubmed.ncbi.nlm.nih.gov/36597064/

8. Polesello, Vania, Zupin, Luisa, Di Lenarda, Roberto, Crovella, Sergio, Segat, Ludovica. 2015. Impact of DEFB1 gene regulatory polymorphisms on hBD-1 salivary concentration. In Archives of oral biology, 60, 1054-8. doi:10.1016/j.archoralbio.2015.03.009. https://pubmed.ncbi.nlm.nih.gov/25939140/

9. Zupin, Luisa, Polesello, Vania, Grasso, Domenico Leonardo, Crovella, Sergio, Segat, Ludovica. 2016. DEFB1 polymorphisms and susceptibility to recurrent tonsillitis in Italian children. In International journal of pediatric otorhinolaryngology, 83, 12-5. doi:10.1016/j.ijporl.2016.01.025. https://pubmed.ncbi.nlm.nih.gov/26968045/