Rs5219
| Orientation | plus |
| is a | snp |
| is | mentioned by |
| dbSNP | rs5219 |
| PheGenI | rs5219 |
| nextbio | rs5219 |
| hapmap | rs5219 |
| 1000 genomes | rs5219 |
| hgdp | rs5219 |
| ensembl | rs5219 |
| gopubmed | rs5219 |
| geneview | rs5219 |
| scholar | rs5219 |
| rs5219 | |
| pharmgkb | rs5219 |
| gwascentral | rs5219 |
| openSNP | rs5219 |
| 23andMe | rs5219 |
| 23andMe all | rs5219 |
| SNP Nexus | |
| SNPshot | rs5219 |
| SNPdbe | rs5219 |
| MSV3d | rs5219 |
| Gene | KCNJ11 |
| Chromosome | 11 |
| Orientation | plus |
| GMAF | 0.2738 |
| Position | 17409572 |
| Reference | GRCh37 37.1/131 |
| Max Magnitude | 2.5 |
| Geno | Mag | Summary |
|---|---|---|
| (C;C) | 0 | normal |
| (C;T) | 1.5 | 1.3x increased risk for type-2 diabetes |
| (T;T) | 2.5 | 2.5x increased risk for type-2 diabetes |
rs5219, also known as E23K, is a SNP in the KCNJ11 gene.
The association between type-1 diabetes and rs5219 is mentioned as being replicated in [PMID 17554300]; there is also a 90% correlation between rs5219 and rs5215.
This SNP is one of 4 relatively common SNPs reported to represent risk for type-2 diabetes in the DESIR prospective study of 3,877 Caucasian participants. Under an additive model, the odds ratio for the minor (risk) allele (T) is 1.15 (CI: 0.95-1.4, p=0.2, ie not significant). But for the 4 SNPs, each risk allele increased type-2 diabetes risk by 1.34x (p=2x10e-6), with an odds ratio of 2.48 (CI: 1.59-3.86) for carriers of 4 or more compared to those with one or none (risk alleles).[PMID 17977958]
Genotyping of ~4000 Chinese as well a meta-analysis concluded that rs5219 was associated with type-2 diabetes in Chinese Han and East Asian populations, under a recessive model showing an odds ratio of 1.25 (CI: 1.04-1.5, p=0.017).[PMID 19498446]
[PMID 18162508] significantly associated p = 0.0034; in 1,630 Japanese subjects with type-2 diabetes and in 1,064 controls
| Neighbor | rs28936678 |
| Distance | 373 |
| Venter snp | |
|---|---|
| Source | plos |
| Gene | KCNJ11 |
| allele | C |
| frequency | |
| sift | TOLERATED |
| HuRef | 1103649619609 |
| Disease Association | Defects in KCNJ11 may contribute to non-insulin-dependent diabetes mellitus (NIDDM), also known as type II diabetes mellitus. |
[PMID 19258437] A Genetic Variant in the IGF2BP2 Gene may Interact with Fetal Malnutrition on Glucose Metabolism.
| GWAS snp | |
|---|---|
| PMID | [PMID 19056611] |
| Trait | Type 2 diabetes |
| Title | Adiposity-related heterogeneity in patterns of type 2 diabetes susceptibility observed in genome wide association data |
| Risk Allele | |
| P-val | 5E-7 |
| Odds Ratio | 1.19 [1.11-1.27] |
| GWAS snp | |
|---|---|
| PMID | [PMID 17463246] |
| Trait | Type 2 diabetes |
| Title | Genome-wide association analysis identifies loci for type 2 diabetes and triglyceride levels |
| Risk Allele | T |
| P-val | 7.0000000000000004E-11 |
| Odds Ratio | 1.14 [1.10-1.19] |
| GWAS snp | |
|---|---|
| PMID | [PMID 17463248] |
| Trait | Type 2 diabetes |
| Title | A genome-wide association study of type 2 diabetes in Finns detects multiple susceptibility variants |
| Risk Allele | T |
| P-val | 7.0000000000000004E-11 |
| Odds Ratio | 1.14 [1.10-1.19] |
[PMID 18972257] Comparison of genetic risk in three candidate genes (TCF7L2, PPARG, KCNJ11) with traditional risk factors for type 2 diabetes in a population-based study--the HUNT study
| OMIM | 600937 |
| Desc | POTASSIUM CHANNEL, INWARDLY RECTIFYING, SUBFAMILY J, MEMBER 11; KCNJ11 |
| Variant | |
| Related | also |
[PMID 20361036] Gene-gene interactions lead to higher risk for development of type 2 diabetes in an ashkenazi jewish population
| ClinVar | |
|---|---|
| Risk | rs5219(A,C,G;A,C,G) |
| Normal | rs5219(T;T) |
| Significance | 2 |
| Disease | Permanent neonatal diabetes mellitus |
| ClinVar | info |
| Gene | KCNJ11 |
| CLNDBN | Permanent neonatal diabetes mellitus |
| Reversed | 0 |
| CLNHGVS | NC_000011.8:g.17366148T>C |
| CLNSRC | GeneReviews |
[PMID 16733889] [Association analysis of 30 type 2 diabetes candidate genes in Chinese Han population].
[PMID 16873704] Association studies of variants in the genes involved in pancreatic beta-cell function in type 2 diabetes in Japanese subjects.
[PMID 17570749] Genetic prediction of future type 2 diabetes.
[PMID 17786212] Heterogeneity in meta-analyses of genome-wide association investigations.
[PMID 17903298] Genome-wide association with diabetes-related traits in the Framingham Heart Study.
[PMID 18224312] Pharmacogenetics: data, concepts and tools to improve drug discovery and drug treatment.
[PMID 18282109] Adaptations to climate in candidate genes for common metabolic disorders.
[PMID 18319073] Using the optimal receiver operating characteristic curve to design a predictive genetic test, exemplified with type 2 diabetes.
[PMID 18423522] Estimating odds ratios in genome scans: an approximate conditional likelihood approach.
[PMID 18426861] Association analysis of type 2 diabetes Loci in type 1 diabetes.
[PMID 18498634] The genetic susceptibility to type 2 diabetes may be modulated by obesity status: implications for association studies.
[PMID 18591388] Assessing the combined impact of 18 common genetic variants of modest effect sizes on type 2 diabetes risk.
[PMID 18678618] Comprehensive association study of type 2 diabetes and related quantitative traits with 222 candidate genes.
[PMID 18689695] Predicting diabetes: clinical, biological, and genetic approaches: data from the Epidemiological Study on the Insulin Resistance Syndrome (DESIR).
[PMID 18689899] Exchangeable models of complex inherited diseases.
[PMID 18694974] Predicting type 2 diabetes based on polymorphisms from genome-wide association studies: a population-based study.
[PMID 18782870] Clinical review: the genetics of type 2 diabetes: a realistic appraisal in 2008.
[PMID 18852197] Metabolic and cardiovascular traits: an abundance of recently identified common genetic variants.
[PMID 19002430] Type 2 diabetes-associated genetic variants discovered in the recent genome-wide association studies are related to gestational diabetes mellitus in the Korean population.
[PMID 19020323] Genotype score in addition to common risk factors for prediction of type 2 diabetes.
[PMID 19033397] Replication study of candidate genes associated with type 2 diabetes based on genome-wide screening.
[PMID 19207020] Meta-analysis in genome-wide association studies.
[PMID 19279076] Genetic predisposition, Western dietary pattern, and the risk of type 2 diabetes in men.
[PMID 19309528] Specific and complete human genome amplification with improved yield achieved by phi29 DNA polymerase and a novel primer at elevated temperature.
[PMID 19323962] Genome-wide association studies in type 2 diabetes.
[PMID 19324937] Previously associated type 2 diabetes variants may interact with physical activity to modify the risk of impaired glucose regulation and type 2 diabetes: a study of 16,003 Swedish adults.
[PMID 19341491] Genome-based prediction of common diseases: methodological considerations for future research.
[PMID 19368707] Contribution of type 2 diabetes associated loci in the Arabic population from Tunisia: a case-control study.
[PMID 19401414] Confirmation of multiple risk Loci and genetic impacts by a genome-wide association study of type 2 diabetes in the Japanese population.
[PMID 19455305] No association of multiple type 2 diabetes loci with type 1 diabetes.
[PMID 19460916] Genetic architecture of type 2 diabetes: recent progress and clinical implications.
[PMID 19502414] Association of 18 confirmed susceptibility loci for type 2 diabetes with indices of insulin release, proinsulin conversion, and insulin sensitivity in 5,327 nondiabetic Finnish men.
[PMID 19602701] Underlying genetic models of inheritance in established type 2 diabetes associations.
[PMID 19862325] PPARG, KCNJ11, CDKAL1, CDKN2A-CDKN2B, IDE-KIF11-HHEX, IGF2BP2 and SLC30A8 are associated with type 2 diabetes in a Chinese population.
[PMID 19956539] How many genetic variants remain to be discovered?
[PMID 20017978] Influence of control selection in genome-wide association studies: the example of diabetes in the Framingham Heart Study.
[PMID 20018041] The effect of multiple genetic variants in predicting the risk of type 2 diabetes.
[PMID 20043853] Prioritizing genes for follow-up from genome wide association studies using information on gene expression in tissues relevant for type 2 diabetes mellitus.
[PMID 20049090] Association between type 2 diabetes loci and measures of fatness.
[PMID 20075150] Utility of genetic and non-genetic risk factors in prediction of type 2 diabetes: Whitehall II prospective cohort study.
[PMID 20079163] Effect of genetic variants in KCNJ11, ABCC8, PPARG and HNF4A loci on the susceptibility of type 2 diabetes in Chinese Han population.
[PMID 20144327] A genomics study of type 2 diabetes mellitus in U.S. Air Force personnel.
[PMID 20161779] Investigation of type 2 diabetes risk alleles support CDKN2A/B, CDKAL1, and TCF7L2 as susceptibility genes in a Han Chinese cohort.
[PMID 20424228] Impact of common variants of PPARG, KCNJ11, TCF7L2, SLC30A8, HHEX, CDKN2A, IGF2BP2, and CDKAL1 on the risk of type 2 diabetes in 5,164 Indians.
[PMID 20712903] Obesity and diabetes genes are associated with being born small for gestational age: results from the Auckland Birthweight Collaborative study.
[PMID 21278902] Genetic risk profiling for prediction of type 2 diabetes.
[PMID 21283728] Genetic variants of diabetes risk and incident cardiovascular events in chronic coronary artery disease.
[PMID 21573802] Association between KCNJ11 gene polymorphisms and risk of type 2 diabetes mellitus in East Asian populations: a meta-analysis in 42,573 individuals.
[PMID 21602532] Type 2 diabetes risk variants and colorectal cancer risk: the Multiethnic Cohort and PAGE studies.
[PMID 22082043] The effect of KCNJ11 polymorphism on the risk of type 2 diabetes: a global meta-analysis based on 49 case-control studies.
[PMID 22377712] Association between type 2 diabetes genetic susceptibility loci and visceral and subcutaneous fat area as determined by computed tomography.
| GET Evidence | |
|---|---|
| KCNJ11-K23E | |
| aa_change | Lys23Glu |
| aa_change_short | K23E |
| impact | protective |
| qualified_impact | Low clinical importance, Likely protective |
| overall_frequency | 0.738148 |
| summary | This variant is associated with decreased risk of type 2 diabetes. It is unclear whether this variant has additive effects, or acts in a dominant or recessive manner. Assuming diabetes has a lifetime risk of 36%, we estimate a decreased risk of around 1-2% per copy of this variant. |
[PMID 23029294] Meta-analysis of the relationship between common type 2 diabetes risk gene variants with gestational diabetes mellitus
