Dnajc27-KO Mouse

Dnajc27, a member of the HSP40 protein family, is associated with body mass index (BMI) as identified in genome-wide association (GWAS) studies [2,3,5,6]. It is involved in the heat shock response pathway, an essential cellular stress response, and may play a role in maintaining protein homeostasis, potentially through its interaction with Hsp70 as suggested by interactome profiling [7].

Genetic studies have shown its associations with multiple health conditions. In a Kuwaiti cohort, the MC4R variant rs17782313 was associated with increased levels of DNAJC27, and increased DNAJC27 levels reduced MC4R-mediated cAMP formation, suggesting a role in appetite regulation and obesity [2]. In a Chinese Han preschool children study, the DNAJC27 rs713586 polymorphism was associated with susceptibility to overweight and obesity, and there was a cumulative effect with SEC16B rs633715 [4]. Also, DNAJC27 levels were significantly higher in plasma, peripheral blood mononuclear cells (PBMCs), and adipose tissue of obese individuals, and it was associated with leptin and resistin, adipokines related to metabolic disorders [3]. Additionally, DNAJC27 was identified as a risk gene associated with a shared genetic basis between inflammatory bowel disease and psoriasis through colocalization and multivariable Mendelian Randomization (MR) analysis [1].

In conclusion, Dnajc27 is significantly associated with obesity-related traits and metabolic disorders, and its role in the heat shock response and protein homeostasis may be crucial in these processes. Its associations with inflammatory bowel disease and psoriasis also highlight its importance in immune-related diseases. Studies on Dnajc27 contribute to understanding the genetic basis of these diseases and may provide potential targets for intervention.

References:

1. Cai, Yangke, Xie, Siyuan, Jia, Xuan, Mao, Jianshan, Ye, Jun. 2023. Integrated analysis of Mendelian Randomization and Bayesian colocalization reveals bidirectional causal association between inflammatory bowel disease and psoriasis. In Annals of medicine, 55, 2281658. doi:10.1080/07853890.2023.2281658. https://pubmed.ncbi.nlm.nih.gov/37988718/

2. Hammad, Maha M, Abu-Farha, Mohamed, Hebbar, Prashantha, Al-Mulla, Fahd, Abubaker, Jehad. 2020. MC4R Variant rs17782313 Associates With Increased Levels of DNAJC27, Ghrelin, and Visfatin and Correlates With Obesity and Hypertension in a Kuwaiti Cohort. In Frontiers in endocrinology, 11, 437. doi:10.3389/fendo.2020.00437. https://pubmed.ncbi.nlm.nih.gov/32733386/

3. Cherian, Preethi T, Al-Khairi, Irina, Sriraman, Devarajan, Abubaker, Jehad A, Abu-Farha, Mohamed. 2018. Increased Circulation and Adipose Tissue Levels of DNAJC27/RBJ in Obesity and Type 2-Diabetes. In Frontiers in endocrinology, 9, 423. doi:10.3389/fendo.2018.00423. https://pubmed.ncbi.nlm.nih.gov/30131766/

4. Peng, Luolan, Gong, Zhaolong, Han, Chao, Huo, Junsheng, Li, Yan. . [Association of polymorphisms in SEC16B, DNAJC27, FTO and MC4R genes with overweight and obesity in Han preschool children]. In Wei sheng yan jiu = Journal of hygiene research, 53, 229-236. doi:10.19813/j.cnki.weishengyanjiu.2024.02.009. https://pubmed.ncbi.nlm.nih.gov/38604958/

5. Williams, Michael J, Almén, Markus S, Fredriksson, Robert, Schiöth, Helgi B. 2012. What model organisms and interactomics can reveal about the genetics of human obesity. In Cellular and molecular life sciences : CMLS, 69, 3819-34. doi:10.1007/s00018-012-1022-5. https://pubmed.ncbi.nlm.nih.gov/22618246/

6. Wen, Wanqing, Cho, Yoon-Shin, Zheng, Wei, Tai, E Shyong, Shu, Xiao-Ou. 2012. Meta-analysis identifies common variants associated with body mass index in east Asians. In Nature genetics, 44, 307-11. doi:10.1038/ng.1087. https://pubmed.ncbi.nlm.nih.gov/22344219/

7. Piette, Benjamin L, Alerasool, Nader, Lin, Zhen-Yuan, Gingras, Anne-Claude, Taipale, Mikko. 2021. Comprehensive interactome profiling of the human Hsp70 network highlights functional differentiation of J domains. In Molecular cell, 81, 2549-2565.e8. doi:10.1016/j.molcel.2021.04.012. https://pubmed.ncbi.nlm.nih.gov/33957083/