Lepr, short for leptin receptor, is a crucial protein that binds to leptin, a hormone regulating food intake and energy expenditure. This interaction is involved in pathways related to metabolism, energy homeostasis, and potentially in disease-associated processes like those related to obesity, diabetes, and cancer. Genetic models, such as gene knockout (KO) or conditional knockout (CKO) mouse models, are valuable in studying Lepr's functions [1,2,3].

Meta-analysis of 16 studies with 7827 subjects suggested that the LEPR Gln223Arg polymorphism may not affect the susceptibility to type 2 diabetes (T2DM) [1]. Another meta-analysis including 5819 cases and 8068 controls found that the LEPR K109R (rs1137100) genetic polymorphism did not significantly affect the overall cancer risk, but was associated with decreased breast cancer susceptibility under the additive genetic model and had associations with lung and gastric cancer in some genetic models [3]. In Mexican patients, the c.326A>G heterozygous genotype of LEPR was linked to an increased risk of colorectal cancer, while the AG haplotype had a protective effect [4]. A study on Chinese Mulao people showed that certain LEPR SNPs were associated with osteoporosis [5]. Also, in the Ukrainian population, the LEPR (rs1137101) polymorphism indicated an increased risk of the metabolic syndrome [6]. One meta-analysis including 5143 T2DM cases and 5021 controls found that rs1137101 (p.R223Q) in LEPR was significantly associated with T2DM in all genetic models [7].

In conclusion, Lepr is essential for maintaining energy homeostasis and metabolism through its interaction with leptin. Studies using genetic models have revealed its associations with multiple diseases including T2DM, various cancers, osteoporosis, and the metabolic syndrome. Understanding Lepr's functions through these models provides insights into the disease mechanisms and may offer potential targets for disease prevention and treatment.

References:

1. Liu, Ying, Chen, Shu-Qin, Jing, Zhao-Hai, Wang, Robin, Wang, Yan-Gang. 2015. Association of LEPR Gln223Arg polymorphism with T2DM: A meta-analysis. In Diabetes research and clinical practice, 109, e21-6. doi:10.1016/j.diabres.2015.05.042. https://pubmed.ncbi.nlm.nih.gov/26094585/

2. Delplanque, Jérôme, Le Collen, Lauriane, Loiselle, Hélène, Froguel, Philippe, Bonnefond, Amélie. 2024. Monoallelic pathogenic variants in LEPR do not cause obesity. In American journal of human genetics, 111, 2668-2674. doi:10.1016/j.ajhg.2024.10.014. https://pubmed.ncbi.nlm.nih.gov/39561769/

3. Shi, Hui, Shu, Hexi, Huang, Changjia, Yang, Yong, Liu, Pengcheng. . Association of LEPR K109R polymorphisms with cancer risk: a systematic review and pooled analysis. In Journal of B.U.ON. : official journal of the Balkan Union of Oncology, 19, 847-54. doi:. https://pubmed.ncbi.nlm.nih.gov/25261678/

4. Partida, Miriam, Gutiérrez, Melva, Ayala, María de la Luz, Alvizo, Carlos Rogelio, Peregrina, Jorge. 2019. LEPR polymorphisms and haplotypes in Mexican patients with colorectal cancer. In Biomedica : revista del Instituto Nacional de Salud, 39, 205-211. doi:10.7705/biomedica.v39i1.4091. https://pubmed.ncbi.nlm.nih.gov/31021558/

5. Ye, Guangbin, Huang, Yandong, Yin, Lianfei, Huang, Xiufeng, Bin, Xiaoyun. . Association between LEPR polymorphism and susceptibility of osteoporosis in Chinese Mulao people. In Artificial cells, nanomedicine, and biotechnology, 50, 10-16. doi:10.1080/21691401.2021.2020279. https://pubmed.ncbi.nlm.nih.gov/35086395/

6. Prodan, Andrii, Dzubanovsky, Ihor, Kamyshnyi, Oleksandr, Pidruchna, Svitlana, Voloshyn, Stanislava. 2023. GHRL, LEP, LEPR genes polymorphism and their association with the metabolic syndrome in the Ukrainian population. In Endocrine regulations, 57, 269-278. doi:10.2478/enr-2023-0030. https://pubmed.ncbi.nlm.nih.gov/38127688/

7. Yang, Ming Ming, Wang, Jun, Fan, Jiao Jie, Teng, Yan, Li, Yan-Bo. 2016. Variations in the Obesity Gene "LEPR" Contribute to Risk of Type 2 Diabetes Mellitus: Evidence from a Meta-Analysis. In Journal of diabetes research, 2016, 5412084. doi:10.1155/2016/5412084. https://pubmed.ncbi.nlm.nih.gov/27195302/