A single study [PMID 17719176] found this SNP to be associated with medication overuse headache (sample consisting of 82 MOH patients). Compared to the His/His genotypes, those carrying two Arg alleles had a significantly higher monthly drug consumption (p = 0.00075) and higher severe depressive scores on the Beck Depression Index (p = 0.003).
His611Arg is also potentially implicated in type-2 diabetes. In a sample of 3,234 high diabetes risk individuals, Arg/Arg carriers had a generally higher insulinogenic index and lower insulin sensitivity levels, while His allele carriers followed the opposite pattern. Arg/Arg carriers also responded strongly to metformin and lifestyle changes, with significantly elevated insulinogenic levels (p = 0.007 for metformin, p = 0.06 for lifestyle changes) and normalized insulin sensitivity. [PMID 18060660] [|Full Text]
[PMID 18568334] His allele associated with estimates of decreased beta cell function in individuals with abnormal glucose regulation
|Disease Association||Defects in WFS1 are the cause of Wolfram syndrome (WFS) (MIM:222300); also known as diabetes insipidus and mellitus with optic atrophy and deafness syndrome (DIDMOAD). It is a rare autosomal recessive disorder characterized by juvenile diabetes mellitus, diabetes insipidus, optic atrophy, deafness and various neurological symptoms.|
[PMID 19258739] Association study of the effect of WFS1 polymorphisms on risk of type 2 diabetes in Japanese population
[PMID 18040659] Replication of the association between variants in WFS1 and risk of type 2 diabetes in European populations.
[PMID 18991055] Association between polymorphisms in SLC30A8, HHEX, CDKN2A/B, IGF2BP2, FTO, WFS1, CDKAL1, KCNQ1 and type 2 diabetes in the Korean population.
[PMID 19115052] Common variations in 4p locus are related to male completed suicide.
[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 19741467] Association of common type 2 diabetes risk gene variants and posttransplantation diabetes mellitus in renal allograft recipients in Korea.
[PMID 21127832] Decreased insulin secretion and increased risk of type 2 diabetes associated with allelic variations of the WFS1 gene: the Data from Epidemiological Study on the Insulin Resistance Syndrome (DESIR) prospective study.
|qualified_impact||Low clinical importance, Uncertain not reviewed|
|summary||This nonsynonymous SNP is associated with Wolfram Syndrome (known as DIDMOAD), which is characterized by early-onset non-autoimmune diabetes mellitus, diabetes insipidus, optic atrophy, and deafness) and to adult Type Two Diabetes Mellitus. The WFS1 gene maps to chromosome 4p16.3. The variant has been shown to be statistically associated with type II diabetes in six UK studies and one study of Ashkenazi Jews (Sandhu, M., et al., Minton et al.).|
[PMID 23257691] Association of rs734312 and rs10010131 polymorphisms in WFS1 gene with type 2 diabetes mellitus: a meta-analysis
[PMID 24477584] Genetic association of IDE, POU2F1, PON1, IL1α and IL1β with type 2 diabetes in Pakistani population
|Disease||not specified Nonsyndromic Hearing Loss WFS1-Related Spectrum Disorders|
|CLNDBN||not specified Nonsyndromic Hearing Loss, Dominant WFS1-Related Spectrum Disorders|
|CLNSRC||HGMD UniProtKB (protein)|
|CLNACC||RCV000038646.10, RCV000339307.1, RCV000404430.1,|