Single-nucleotide variant rs1800139 of the LRP1 gene as a factor in the development of obesity in children




low-density lipoprotein receptor-related protein 1 gene, analysis of single nucleotide gene variants, children, metabolically unhealthy obesity, metabolically healthy obesity


In the development of postnatal obesity and associated metabolic disorders, genetic features occupy a prominent place among various obesogenic factors. One of the genes that controls adipogenesis and determines the development of adipose tissue is the human low-density lipoprotein receptor-related protein 1 (LRP1) gene.

The aim: study of the frequency of SNVs of the LRP1 gene in children with different phenotypes of obesity.

Materials and methods. 253 obese children aged 6-18 years were examined. The main group (n=153) was made up of children with metabolically unhealthy obesity (MUO) according to IDEFICS 2014 criteria. The control group (n=100) was made up of children with metabolically healthy obesity (MHO). All children underwent a general clinical, immunobiochemical examination (Synevo, Ukraine). Whole-genome sequencing (CeGat, Germany) was performed in 31 children of the primary and 21 children of the control group. Static analysis: variational analysis, Wald analysis, calculation of χ2, Kramer's independence test, Spearman's correlation analysis, ROC analysis.

Results. As a result of testing statistical hypotheses based on the conjugation table of features from 743 SNVs of 86 candidate genes studied, the greatest association with MUO was found in SNV rs1800139 LRP1 (V=0.44). In patients with MHO, the CC genotype was significantly less common (p<0.05) and the TT genotype of SNV rs1800139 of the LRP1 gene was more often registered than in the general human population (p<0.02). In patients with MUO, both homozygous genotypes of SNV rs1800139 of the LRP1 gene occurred significantly less frequently than in the general human population (p<0.05). Among patients with MUO, the TT genotype of SNV rs1800139 of the LRP1 gene occurred significantly less often compared to the group of patients with MHO (p<0.01).

Conclusions. The СT genotype SNV rs1800139 of the LRP1 gene is highly associated with the presence of MUO and the development of dyslipidemia in children.

The research was carried out in accordance with the principles of the Declaration of Helsinki. The research protocol was approved by the Local Ethics Committee of the institution mentioned in the work. Informed consent of parents or their guardians was obtained for conducting research.

The authors declare no conflict of interest.


Abaturov A, Nikulina A. (2022). Taste preferences and obesity. Pediatr Pol. 97(1): 1-6.

Abaturov OE, Nikulina AO. (2020). Phenotypes of obesity in children, clinical manifestations and genetic associations. Child health. 4(15): 238-251.

Actis Dato V, Chiabrando GA. (2018). The Role of Low-Density Lipoprotein Receptor-Related Protein 1 in Lipid Metabolism, Glucose Homeostasis and Inflammation. Int J Mol Sci. 19(6):1780.; PMid:29914093 PMCid:PMC6032055

Alberti KG, Zimmet P, Kaufman F et al. (2017). The IDF consensus definition of the metabolic syndrome in children and adolescents. International Diabetes Federation. 17-19. URL: Accessed 2 February 2024.

Au DT, Strickland DK, Muratoglu SC. (2017). The LDL Receptor-Related Protein 1: At the Crossroads of Lipoprotein Metabolism and Insulin Signaling. J Diabetes Res. 2017: 8356537.; PMid:28584820 PMCid:PMC5444004

Baker JL, Bjerregaard LG. (2023). Advancing precision public health for obesity in children. Rev Endocr Metab Disord. 24(5): 1003-1010.; PMid:37055611 PMCid:PMC10101815

Bradwisch SA, Smith EM, Mooney C, Scaccia D. (2020). Obesity in children and adolescents: An overview. Nursing. 50(11): 60-66.; PMid:33105431

Buniello A, MacArthur JAL et al. (2019). The NHGRI-EBI GWAS Catalog of published genome-wide association studies, targeted arrays and summary statistics. Nucleic Acids Res. 8; 47(D1): D1005-D1012.; PMid:30445434 PMCid:PMC6323933

Chen J, Su Y, Pi S et al. (2021). The Dual Role of Low-Density Lipoprotein Receptor-Related Protein 1 in Atherosclerosis. Front Cardiovasc Med. 28; 8: 682389. doi: 10.3389/fcvm.2021.682389. Erratum in: Front Cardiovasc Med. 2023 Apr 21; 10: 1179643.; PMid:37153455 PMCid:PMC10162809

De Geest B, Mishra M. (2023). New Perspectives on Cholesterol and Lipoprotein Metabolism. Int J Mol Sci. 11; 24(14): 11298.; PMid:37511058 PMCid:PMC10379683

Deelen P, Bonder MJ, van der Velde KJ et al. (2014). Genotype harmonizer: automatic strand alignment and format conversion for genotype data integration. BMC Res Notes. 7: 901.; PMid:25495213 PMCid:PMC4307387

Draznin B, Aroda VR, Bakris G et al. (2022); American Diabetes Association Professional Practice Committee. 6. Glycemic targets: Standards of Medical Care in Diabetes - 2022. Diabetes Care. 45; Suppl 1: 83-96.; PMid:34964868

Elkins C, Fruh Sh, Jones L et al. (2019). Clinical Practice Recommendations for Pediatric Dyslipidemia. Journal of Pediatric Health Care. 33(4): 494-504.; PMid:31227123

Flynn JT, Kaelber DC, Baker-Smith CM et al. (2017). Subcommittee on screening and management of high blood pressure in children. Clinical Practice Guideline for Screening and Management of High Blood Pressure in Children and Adolescents. Pediatrics. 140(3): e20171904.; PMid:28827377

Frazier-Wood AC, Kabagambe EK, Wojczynski MK et al. (2013). The association between LRP-1 variants and chylomicron uptake after a high fat meal. Nutr Metab Cardiovasc Dis. 23(11): 1154-1158.; PMid:23484911 PMCid:PMC3686991

Hasan MM, Fahim SM, Das S et al. (2021). Association of plasma low-density lipoprotein receptor-related protein-1 (LRP1) with undernutrition: a case-control study in Bangladeshi adults. Biomarkers. 26(7): 625-631.; PMid:34433325

Hofmann SM, Zhou L, Perez-Tilve D et al. (2007). Adipocyte LDL receptor-related protein-1 expression modulates postprandial lipid transport and glucose homeostasis in mice. J Clin Invest. 117(11): 3271-3282.; PMid:17948131 PMCid:PMC2030460

Hongshan J, Rong L, Shou-Wei D et al. (2014). Skewer: a fast and accurate adapter trimmer for next-generation sequencing paired-end reads. In BMC Bioinformatics. 15: 182.; PMid:24925680 PMCid:PMC4074385

Jaeschke A, Hui DY. (2021). LDL receptor-related protein 1 and its interacting partners in tissue homeostasis. Curr Opin Lipidol. 32(5): 301-307.; PMid:34310383 PMCid:PMC8534846

Jebeile H, Kelly AS, O'Malley G et al. (2022). Obesity in children and adolescents: epidemiology, causes, assessment, and management. Lancet Diabetes Endocrinol. 10(5): 351-365.; PMid:35248172

Karczewski KJ, Francioli LC, Tiao G et al. (2020). The mutational constraint spectrum quantified from variation in 141,456 humans. Nature. 581: 434-443.

Landrum MJ, Lee JM, Benson M et al. (2018). ClinVar: improving access to variant interpretations and supporting evidence. Nucleic Acids Res. 46(D1): D1062-D1067.; PMid:29165669 PMCid:PMC5753237

Lee JD, Hsiao KM, Chang PJ at al. (2017). A common polymorphism decreases LRP1 mRNA stability and is associated with increased plasma factor VIII levels. Biochim Biophys Acta Mol Basis Dis. 1863(6): 1690-1698.; PMid:28431990

Li D, Luo ZY, Chen Y et al. (2020). LRP1 and APOA1 Polymorphisms: Impact on Warfarin International Normalized Ratio-Related Phenotypes. J Cardiovasc Pharmacol. 76(1): 71-76.; PMid:32282500

Li D, Zhu H, Luo ZY et al. (2020). LRP1 polymorphisms associated with warfarin stable dose in Chinese patients: a stepwise conditional analysis. Pharmacogenomics. 21(16): 1169-1178.; PMid:33094665

Li H, Durbin R. (2009). Fast and accurate short read alignment with Burrows‐Wheeler transform. Bioinformatics. 25(14): 1754-1760.; PMid:19451168 PMCid:PMC2705234

Li W, O'Neill KR, Haft DH et al. (2021). RefSeq: expanding the Prokaryotic Genome Annotation Pipeline reach with protein family model curation. Nucleic Acids Res. 49(D1): D1020-D1028.; PMid:33270901 PMCid:PMC7779008

Lim CY, In J. (2019). Randomization in clinical studies [published correction appears in Korean J Anesthesiol. 72(4): 396]. Korean J Anesthesiol. 72(3): 221-232.; PMid:30929415 PMCid:PMC6547231

Lister NB, Baur LA, Felix JF et al. (2023). Child and adolescent obesity. Nat Rev Dis Primers. 9(1): 24.; PMid:37202378

Liu X, Li C, Mou C et al. (2020). dbNSFP v4: a comprehensive database of transcript-specific functional predictions and annotations for human nonsynonymous and splice-site SNVs. Genome Med. 12(1): 103.; PMid:33261662 PMCid:PMC7709417

Masson O, Chavey C, Dray C et al. (2009). LRP1 receptor controls adipogenesis and is up-regulated in human and mouse obese adipose tissue. PLoS One. 4(10): e7422.; PMid:19823686 PMCid:PMC2758584

Mose LE, Wilkerson MD, Hayes DN et al. (2014). ABRA: improved coding indel detection via assembly-based realignment. Bioinformatics. 30(19): 2813-2815.; PMid:24907369 PMCid:PMC4173014

Mueller PA, Kojima Y, Huynh KT et al. (2022). Macrophage LRP1 (Low-Density Lipoprotein Receptor-Related Protein 1) Is Required for the Effect of CD47 Blockade on Efferocytosis and Atherogenesis-Brief Report. Arterioscler Thromb Vasc Biol. 42(1): e1-e9.; PMid:34758632 PMCid:PMC8702482

Niehaus A, Azzariti DR, Harrison SM et al. (2019). A survey assessing adoption of the ACMG-AMP guidelines for interpreting sequence variants and identification of areas for continued improvement. Genet Med. 21(8): 1699-1701.; PMid:30670879 PMCid:PMC7233466

Peplies J, Börnhorst C, Günther K et al. (2016). IDEFICS consortium. Longitudinal associations of lifestyle factors and weight status with insulin resistance (HOMA-IR) in preadolescent children: the large prospective cohort study IDEFICS. Int J Behav Nutr Phys Act. 13(1): 97.; PMid:27590045 PMCid:PMC5009569

Rakateli L, Huchzermeier R, van der Vorst EPC. (2023). AhR, PXR and CAR: From Xenobiotic Receptors to Metabolic Sensors. Cells. 12(23): 2752.; PMid:38067179 PMCid:PMC10705969

Smith CE, Tucker KL, Lee YC et al. (2013). Low-density lipoprotein receptor-related protein 1 variant interacts with saturated fatty acids in Puerto Ricans. Obesity (Silver Spring). 21(3): 602-608.; PMid:23404896 PMCid:PMC3630241

Uner AA, Hou Z-Sh, Aydogan A et al. (2022). GABAergic LRP1 is a key link between obesity and memory function. bioRxiv.

Uner AA, Yang WM, Kang MC et al. (2023). LRP1 mediates leptin transport by coupling with the short-form leptin receptor in the choroid plexus. 2023.07.03.547520.

Vučinić N, Stokić E, Djan I et al. (2017). The LRP1 Gene Polymorphism is associated with Increased Risk of Metabolic Syndrome Prevalence in the Serbian Population. Balkan J Med Genet. 20(1): 51-58.; PMid:28924541 PMCid:PMC5596822

Wang H, Ma Y. (2023). The Potential of Vitamin K as a Regulatory Factor of Bone Metabolism-A Review. Nutrients. 15(23):4935.; PMid:38068793 PMCid:PMC10708186

Yang Z, Danzeng A, Liu Q et al. (2024). The Role of Nuclear Receptors in the Pathogenesis and Treatment of Non-alcoholic Fatty Liver Disease. Int J Biol Sci. 20(1):113-126.; PMid:38164174 PMCid:PMC10750283






Original articles