rs5219, also known as E23K, is a SNP in the KCNJ11 gene.
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]
|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.
|Trait||Type 2 diabetes|
|Title||Adiposity-related heterogeneity in patterns of type 2 diabetes susceptibility observed in genome wide association data|
|Odds Ratio||1.19 [1.11-1.27]|
|Trait||Type 2 diabetes|
|Title||Genome-wide association analysis identifies loci for type 2 diabetes and triglyceride levels|
|Odds Ratio||1.14 [1.10-1.19]|
|Trait||Type 2 diabetes|
|Title||A genome-wide association study of type 2 diabetes in Finns detects multiple susceptibility variants|
|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[PMID 20361036] Gene-gene interactions lead to higher risk for development of type 2 diabetes in an ashkenazi jewish population
|Disease||Diabetes mellitus type 2 Exercise stress response Permanent neonatal diabetes mellitus|
|CLNDBN||Diabetes mellitus type 2 Exercise stress response, impaired, association with Permanent neonatal diabetes mellitus|
|CLNSRC||GeneReviews OMIM Allelic Variant|
|CLNACC||RCV000009214.1, RCV000009215.1, RCV000020356.1,|
[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.
|qualified_impact||Low clinical importance, Likely protective|
|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
[PMID 23690305] Genetic variants and the risk of gestational diabetes mellitus: a systematic review
[PMID 22749234] Contribution of common variants of ENPP1, IGF2BP2, KCNJ11, MLXIPL, PPARγ, SLC30A8 and TCF7L2 to the risk of type 2 diabetes in Lebanese and Tunisian Arabs
[PMID 23298195] Association study of genetic variants of 17 diabetes-related genes/loci and cardiovascular risk and diabetic nephropathy in the Chinese She population.
[PMID 23458876] ACE I/D and MTHFR C677T polymorphisms are significantly associated with type 2 diabetes in Arab ethnicity: a meta-analysis.
[PMID 23462794] Identification of CpG-SNPs associated with type 2 diabetes and differential DNA methylation in human pancreatic islets.
[PMID 23544998] Association of TRPC1 gene polymorphisms with type 2 diabetes and diabetic nephropathy in Han Chinese population.
[PMID 9867219] Missense mutations in the pancreatic islet beta cell inwardly rectifying K+ channel gene (KIR6.2/BIR): a meta-analysis suggests a role in the polygenic basis of Type II diabetes mellitus in Caucasians.
[PMID 15579791] Polymorphisms of the SUR1 (ABCC8) and Kir6.2 (KCNJ11) genes predict the conversion from impaired glucose tolerance to type 2 diabetes. The Finnish Diabetes Prevention Study.
[PMID 15797964] Analysis of separate and combined effects of common variation in KCNJ11 and PPARG on risk of type 2 diabetes.
[PMID 17463249] Replication of genome-wide association signals in UK samples reveals risk loci for type 2 diabetes.