rs2167270

This is a 5 prime utr variant variant in the LEP gene.

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ClinVar annotation

Likely Benign★★★☆
3 submitters1 publication

Monogenic Non-Syndromic Obesity; Obesity due to congenital leptin deficiency

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Research that mentions this SNP (5)

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Genetic variation of FTO: rs1421085 T>C, rs8057044 G>A, rs9939609 T>A, and copy number (CNV) in Mexican Mayan school‐aged children with obesity/overweight and with normal weight
ReviewLizbeth González‐Herrera et al.(2019)· American Journal of Human Biology

A literature review of 70 studies examining single nucleotide polymorphisms (SNPs) associated with obesity in Mexican populations published 2011-2021. The authors identified SNPs with differential behavior in Mexican compared to Caucasian populations, including rs17782313 (MC4R), rs6548238 (TMEM18), rs6265 (BDNF), rs7498665 (SH2B1), and notably rs6232 (PCSK1) associated with early-onset obesity in Mexican youth. The review emphasizes ethnicity-dependent genetic effects on BMI heritability (40-70%) and highlights genes involved in cholesterol metabolism and adipokine signaling pathways.

Traits studied:AdiposityBlood pressureBody mass index (BMI)Cardiovascular risk factorsDyslipidemiaInsulin resistanceMetabolic syndromeObesityOverweightType 2 diabetes
PubMedDOIMetascience Observatory
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Genetic variation at the CELF1 (CUGBP, elav‐like family member 1 gene) locus is genome‐wide associated with Alzheimer's disease and obesity
ReviewAnke Hinney et al.(2014)· American Journal of Medical Genetics Part B: Neuropsychiatric Genetics

This literature review examines the influence of genetic polymorphisms on obesity development and adaptive responses to physical activity, focusing on five candidate genes: COMT (rs4680, Val158Met), DRD2 (rs1800497 Taq1A and rs1799732), FABP2 (rs1799883, Ala54Thr), FTO (rs9939609, A/T), and UCP1 (rs1800592, A-3826G). The review synthesizes molecular mechanisms, phenotypic associations, and implications for human health and training adaptations, noting that physical activity reduces the FTO genetic effect on obesity risk by 30-80% and that various polymorphisms show differential impacts on body composition and metabolic responses to exercise.

Traits studied:Adipose tissue distributionAthletic performanceBody Mass Index (BMI)Body compositionExercise adaptationFat massMuscle massObesityPhysical activity responseWeight loss
PubMedDOIMetascience Observatory
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Evaluation of 64 candidate single nucleotide polymorphisms as risk factors for neural tube defects in a large Irish study population
AssociationN=2,079Tonia C. Carter et al.(2011)· American Journal of Medical Genetics Part A

This case-control and family-based study evaluated 64 SNPs in 34 genes for associations with spina bifida in 558 Irish case-families and 994 controls. Spina bifida was significantly associated with LEPR rs1805134 (GRR: 1.5, P = 0.0264) and COMT rs737865 (GRR: 1.4, P = 0.0206), with additional confirmations of previous findings in MTHFR 677C>T and other genes, suggesting roles for leptin signaling and methylation pathways in neural tube defect pathogenesis.

Traits studied:Neural tube defectsSpina bifida
PubMedDOIMetascience Observatory
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Association of IL10 and Other immune response‐ and obesity‐related genes with prostate cancer in CLUE II
AssociationN=516Ming‐Hsi Wang et al.(2009)· The Prostate

Nested case-control study of 258 prostate cancer cases and 258 matched controls in the CLUE II prospective cohort examining genetic variants in inflammation and obesity-related genes. The IL10 -1082G>A variant (rs1800896, A allele) was positively associated with prostate cancer risk (AG vs GG: OR=1.69, 95% CI 1.10-2.60; AA vs GG: OR=1.81, 95% CI 1.11-2.96), while a TLR4 variant (rs4986790) showed inverse association, and no consistent associations were found for obesity-related gene variants.

Traits studied:Prostate cancer
PubMedDOIMetascience Observatory
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Leptin and leptin receptor genotypes and colon cancer: Gene–gene and gene–lifestyle interactions
AssociationN=3,532Martha L. Slattery et al.(2008)· International Journal of Cancer

Case-control study of 1,567 colon cancer cases and 1,965 controls examining leptin (LEP) and leptin receptor (LEPR) genetic variants. The AA genotype of LEP rs2167270 was associated with reduced colon cancer risk (OR 0.79, 95% CI 0.64-0.98). Significant gene-gene and gene-lifestyle interactions were observed with aspirin/NSAID use, insulin pathway genes (IGF1, IRS2), and vitamin D receptor (VDR) polymorphisms, suggesting mechanisms independent of energy balance.

Traits studied:Colon cancerColorectal cancer
PubMedDOIMetascience Observatory

About LEP

This gene encodes a protein that is secreted by white adipocytes into the circulation and plays a major role in the regulation of energy homeostasis. Circulating leptin binds to the leptin receptor in the brain, which activates downstream signaling pathways that inhibit feeding and promote energy expenditure. This protein also has several endocrine functions, and is involved in the regulation of immune and inflammatory responses, hematopoiesis, angiogenesis, reproduction, bone formation and wound healing. Mutations in this gene and its regulatory regions cause severe obesity and morbid obesity with hypogonadism in human patients. A mutation in this gene has also been linked to type 2 diabetes mellitus development. [provided by RefSeq, Aug 2017]

View all LEP variants →

Gene information from NCBI Gene. Variant classifications from ClinVar.

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