Have questions? Visit https://www.reddit.com/r/SNPedia


From SNPedia

Geno Mag Summary
(A;A) 0 1x normal risk of T2D
(T;T) 0
ReferenceGRCh38 38.1/142
is asnp
is mentioned by
1000 genomesrs1111875
23andMe allrs1111875
SNP Nexus

GWAS Ctlgrs1111875
Max Magnitude0
? (A;A) (A;G) (G;G) 28
rs1111875 is a SNP of the HHEX homeobox gene. In several studies, it has been associated with risk for type-2 diabetes (T2D).

In a study of 500 unrelated Caucasian T2D patients, the rs1111875(G) allele was overrepresented; the odds ratio was 1.68 (CI: 1.19-2.35, p=0.003). In this population, the population attributable risk for this allele was estimated to be 36%.[PMID 18231124]

In a study of ~400 Japanese, rs1111875(G) was also associated with type-2 diabetes (odds ratio 1.42, CI: 1.13-1.78, p=0.0024). Heterozygous and homozygous carriers of the risk allele had odds ratios of 1.31 (CI: 0.97-1.77, p=0.0810) and 2.40 (CI: 1.34-4.32, p=0.0028) relative to non-carriers.[PMID 17971426]

And in a third study, 1,630 Japanese patients were also found to have this SNP significantly overrepresented (p=0.0064).[PMID 18162508]

[PMID 18477659] rs1111875 replicated as significant for type-2 diabetes risk in 1,900 Japanese patients, with odds ratio of 1.27 (CI: 1.14-1.40, p = 1.4 x 10e-5)

[PMID 18437351] 1,638 type 2 diabetes patients and 1,858 controls

  • rs1111875 non-significant

[PMID 19117022] rs7923837 and rs1111875 were significantly associated with decreased insulin secretion and lower insulinogenic index. Reduced insulin clearance was also observed in heterozygous carriers of rs1111875

SNP rs1111875
PubMedID [PMID 17293876]
Condition Type 2 diabetes
Risk Allele G
pValue 3.00E-006
OR 1.19
95% CI 0.82-1.56

[PMID 19258437OA-icon.png] A Genetic Variant in the IGF2BP2 Gene may Interact with Fetal Malnutrition on Glucose Metabolism.

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 C
P-val 6E-10
Odds Ratio 1.13 [1.08-1.17]
GWAS snp
PMID [PMID 17463248OA-icon.png]
Trait Type 2 diabetes
Title A genome-wide association study of type 2 diabetes in Finns detects multiple susceptibility variants
Risk Allele C
P-val 6E-10
Odds Ratio 1.13 [1.09-1.17]
GWAS snp
PMID [PMID 19401414OA-icon.png]
Trait Type 2 diabetes
Title Confirmation of multiple risk loci and genetic impacts by a genome-wide association study of type 2 diabetes in the Japanese population
Risk Allele C
P-val 7E-12
Odds Ratio 1.21 [1.15-1.28]
[PMID 20041287OA-icon.png] Polymorphisms of TCF7L2 and HHEX genes in Chinese women with polycystic ovary syndrome

[PMID 20490451] Type 2 diabetes risk alleles near ADCY5, CDKAL1 and HHEX-IDE are associated with reduced birthweight

[PMID 20647405OA-icon.png] No Association between FTO or HHEX and Endometrial Cancer Risk

[PMID 21059810] Meta-analysis of the effect of HHEX gene polymorphism on the risk of type 2 diabetes

[PMID 20927120] Variations in/nearby genes coding for JAZF1, TSPAN8/LGR5 and HHEX-IDE and risk of type 2 diabetes in Han Chinese

[PMID 21510814] Association of Genetic Variations in TCF7L2, SLC30A8, HHEX, LOC387761, and EXT2 with Type 2 Diabetes Mellitus in Tunisia

[PMID 22506066OA-icon.png] Genetic Variants of IDE-KIF11-HHEX at 10q23.33 Associated with Type 2 Diabetes Risk: A Fine-Mapping Study in Chinese Population

[PMID 22569928OA-icon.png] Analysis of common type 2 diabetes mellitus genetic risk factors in new-onset diabetes after transplantation in kidney transplant patients medicated with tacrolimus

[PMID 17786204OA-icon.png] Polymorphisms within novel risk loci for type 2 diabetes determine beta-cell function.

[PMID 17786212OA-icon.png] Heterogeneity in meta-analyses of genome-wide association investigations.

[PMID 17827400] Studies of association of variants near the HHEX, CDKN2A/B, and IGF2BP2 genes with type 2 diabetes and impaired insulin release in 10,705 Danish subjects: validation and extension of genome-wide association studies.

[PMID 17928989] Variations in the HHEX gene are associated with increased risk of type 2 diabetes in the Japanese population.

[PMID 18039816] A candidate type 2 diabetes polymorphism near the HHEX locus affects acute glucose-stimulated insulin release in European populations: results from the EUGENE2 study.

[PMID 18224312OA-icon.png] Pharmacogenetics: data, concepts and tools to improve drug discovery and drug treatment.

[PMID 18264689] Polymorphisms in the TCF7L2, CDKAL1 and SLC30A8 genes are associated with impaired proinsulin conversion.

[PMID 18423522OA-icon.png] Estimating odds ratios in genome scans: an approximate conditional likelihood approach.

[PMID 18426861OA-icon.png] Association analysis of type 2 diabetes Loci in type 1 diabetes.

[PMID 18443202OA-icon.png] Association analysis in african americans of European-derived type 2 diabetes single nucleotide polymorphisms from whole-genome association studies.

[PMID 18461161OA-icon.png] Post genome-wide association studies of novel genes associated with type 2 diabetes show gene-gene interaction and high predictive value.

[PMID 18469204OA-icon.png] Implication of genetic variants near TCF7L2, SLC30A8, HHEX, CDKAL1, CDKN2A/B, IGF2BP2, and FTO in type 2 diabetes and obesity in 6,719 Asians.

[PMID 18533027OA-icon.png] Worldwide population differentiation at disease-associated SNPs.

[PMID 18556337OA-icon.png] Impact of diabetes susceptibility loci on progression from pre-diabetes to diabetes in at-risk individuals of the diabetes prevention trial-type 1 (DPT-1).

[PMID 18591388OA-icon.png] Assessing the combined impact of 18 common genetic variants of modest effect sizes on type 2 diabetes risk.

[PMID 18633108OA-icon.png] Common variants in CDKAL1, CDKN2A/B, IGF2BP2, SLC30A8, and HHEX/IDE genes are associated with type 2 diabetes and impaired fasting glucose in a Chinese Han population.

[PMID 18689899OA-icon.png] Exchangeable models of complex inherited diseases.

[PMID 18694974OA-icon.png] Predicting type 2 diabetes based on polymorphisms from genome-wide association studies: a population-based study.

[PMID 18782870OA-icon.png] Clinical review: the genetics of type 2 diabetes: a realistic appraisal in 2008.

[PMID 18852197OA-icon.png] Metabolic and cardiovascular traits: an abundance of recently identified common genetic variants.

[PMID 18991055] Association between polymorphisms in SLC30A8, HHEX, CDKN2A/B, IGF2BP2, FTO, WFS1, CDKAL1, KCNQ1 and type 2 diabetes in the Korean population.

[PMID 19001172OA-icon.png] Analyses of the National Institute on Aging Late-Onset Alzheimer's Disease Family Study: implication of additional loci.

[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 19008344OA-icon.png] Association analysis of variation in/near FTO, CDKAL1, SLC30A8, HHEX, EXT2, IGF2BP2, LOC387761, and CDKN2B with type 2 diabetes and related quantitative traits in Pima Indians.

[PMID 19020323OA-icon.png] Genotype score in addition to common risk factors for prediction of type 2 diabetes.

[PMID 19033397OA-icon.png] Replication study of candidate genes associated with type 2 diabetes based on genome-wide screening.

[PMID 19056611OA-icon.png] Adiposity-related heterogeneity in patterns of type 2 diabetes susceptibility observed in genome-wide association data.

[PMID 19096518OA-icon.png] Novel association of HK1 with glycated hemoglobin in a non-diabetic population: a genome-wide evaluation of 14,618 participants in the Women's Genome Health Study.

[PMID 19161620OA-icon.png] An open access database of genome-wide association results.

[PMID 19228808OA-icon.png] Type 2 diabetes risk alleles are associated with reduced size at birth.

[PMID 19279076OA-icon.png] Genetic predisposition, Western dietary pattern, and the risk of type 2 diabetes in men.

[PMID 19324937OA-icon.png] 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 19341491OA-icon.png] Genome-based prediction of common diseases: methodological considerations for future research.

[PMID 19455305OA-icon.png] No association of multiple type 2 diabetes loci with type 1 diabetes.

[PMID 19460916OA-icon.png] Genetic architecture of type 2 diabetes: recent progress and clinical implications.

[PMID 19502414OA-icon.png] 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 19615048OA-icon.png] Type 2 diabetes gene TCF7L2 polymorphism is not associated with fetal and postnatal growth in two birth cohort studies.

[PMID 19741467] Association of common type 2 diabetes risk gene variants and posttransplantation diabetes mellitus in renal allograft recipients in Korea.

[PMID 19862325OA-icon.png] PPARG, KCNJ11, CDKAL1, CDKN2A-CDKN2B, IDE-KIF11-HHEX, IGF2BP2 and SLC30A8 are associated with type 2 diabetes in a Chinese population.

[PMID 19956539OA-icon.png] How many genetic variants remain to be discovered?

[PMID 20017978OA-icon.png] Influence of control selection in genome-wide association studies: the example of diabetes in the Framingham Heart Study.

[PMID 20018041OA-icon.png] The effect of multiple genetic variants in predicting the risk of type 2 diabetes.

[PMID 20043853OA-icon.png] Prioritizing genes for follow-up from genome wide association studies using information on gene expression in tissues relevant for type 2 diabetes mellitus.

[PMID 20049090OA-icon.png] Association between type 2 diabetes loci and measures of fatness.

[PMID 20075150OA-icon.png] Utility of genetic and non-genetic risk factors in prediction of type 2 diabetes: Whitehall II prospective cohort study.

[PMID 20080751OA-icon.png] Long-range gene regulation links genomic type 2 diabetes and obesity risk regions to HHEX, SOX4, and IRX3.

[PMID 20126254OA-icon.png] Rare variants create synthetic genome-wide associations.

[PMID 20144318OA-icon.png] A strategy for analyzing gene-nutrient interactions in type 2 diabetes.

[PMID 20144327OA-icon.png] A genomics study of type 2 diabetes mellitus in U.S. Air Force personnel.

[PMID 20161779OA-icon.png] Investigation of type 2 diabetes risk alleles support CDKN2A/B, CDKAL1, and TCF7L2 as susceptibility genes in a Han Chinese cohort.

[PMID 20424228OA-icon.png] 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 20532014OA-icon.png] The epidemiology of diabetes in Korea: from the economics to genetics.

[PMID 20550665OA-icon.png] Association study of genetic variants in eight genes/loci with type 2 diabetes in a Han Chinese population.

[PMID 20712903OA-icon.png] Obesity and diabetes genes are associated with being born small for gestational age: results from the Auckland Birthweight Collaborative study.

[PMID 21056935] Quantitative assessment of the influence of hematopoietically expressed homeobox variant (rs1111875) on type 2 diabetes risk.

[PMID 21278902OA-icon.png] Genetic risk profiling for prediction of type 2 diabetes.

[PMID 21283728OA-icon.png] Genetic variants of diabetes risk and incident cardiovascular events in chronic coronary artery disease.

[PMID 22237986OA-icon.png] Genetic susceptibility to type 2 diabetes and breast cancer risk in women of European and African ancestry.

[PMID 22377712] Association between type 2 diabetes genetic susceptibility loci and visceral and subcutaneous fat area as determined by computed tomography.

[PMID 23036584] Discovery by the Epistasis Project of an epistatic interaction between the GSTM3 gene and the HHEX/IDE/KIF11 locus in the risk of Alzheimer's disease

GET Evidence
impact pathogenic
qualified_impact Insufficiently evaluated pathogenic
overall_frequency 0.34127

[PMID 22438186] A SNP in G6PC2 predicts insulin secretion in type 1 diabetes

GWAS snp
PMID [PMID 24509480OA-icon.png]
Trait Type 2 diabetes
Title Genome-wide trans-ancestry meta-analysis provides insight into the genetic architecture of type 2 diabetes susceptibility.
Risk Allele C
P-val 3E-19
Odds Ratio 1.15 [1.11-1.19]
GWAS snp
PMID [PMID 23945395]
Trait Type 2 diabetes
Title Genome-wide association study identifies three novel loci for type 2 diabetes.
Risk Allele C
P-val 2E-8
Odds Ratio 1.14 [1.09-1.20]

[PMID 26299860] [The HHEX rs1111875A/G gene polymorphism is associated with susceptibility to type 2 diabetes in the Iranian population]

[PMID 27310578] Replication and Relevance of Multiple Susceptibility Loci Discovered from Genome Wide Association Studies for Type 2 Diabetes in an Indian Population.