rs7944584

This is a intron variant variant in the MADD gene.

▶

GWAS Catalog Trait Associations (4)

Genome-wide significant associations (p < 5×10⁻⁸) from the NHGRI-EBI GWAS Catalog.

insulin measurement

Huyghe JR et al. “Exome array analysis identifies new loci and low-frequency variants influencing insulin processing and secretion.” Nature Genetics 45(2):197-201 (2013)
Allele T
OR 0.07
p 5.0e-25
N 8,229
Large GWAS
European

blood glucose amount

Lagou V et al. “Sex-dimorphic genetic effects and novel loci for fasting glucose and insulin variability.” Nature Communications 12(1):24 (2021)
Allele A
OR 0.02
p 3.0e-24
N 140,595
Large GWAS
European
Wessel J et al. “Low-frequency and rare exome chip variants associate with fasting glucose and type 2 diabetes susceptibility.” Nature Communications 6:5897 (2015)
Allele A
OR 0.02
p 5.0e-12
N 60,564
Large GWAS
multi-ancestry
Manning AK et al. “A genome-wide approach accounting for body mass index identifies genetic variants influencing fasting glycemic traits and insulin resistance.” Nature Genetics 44(6):659-69 (2012)
Allele A
OR 0.03
p 4.0e-13
N 58,074
Large GWAS
European
Dupuis J et al. “New genetic loci implicated in fasting glucose homeostasis and their impact on type 2 diabetes risk.” Nature Genetics 42(2):105-116 (2010)
Allele A
OR 0.02
p 2.0e-18
N 46,186
Large GWAS
European
▶

Research that mentions this SNP (3)

▶
A Diabetes-Associated Genetic Variant is Associated with Diastolic Dysfunction and Cardiovascular Disease
AssociationN=15,215John Molvin et al.(2020)· ESC Heart Failure

This association study examined 43 diabetes-related SNPs in relation to diastolic dysfunction and cardiovascular disease across two Swedish cohorts. HNF1B rs757210 (T-allele) was the main finding, associated with prevalent diastolic dysfunction in both the discovery cohort (MPP-RES; OR 1.21, P=0.024) and replication cohort (VARA; OR 1.38, P=0.042), and with increased risk of incident CVD (HR 1.05, P=0.042) but not CHF over 30+ years of follow-up.

Traits studied:Cardiovascular diseaseCongestive heart failureDiastolic dysfunctionType 2 diabetes
PubMedDOIMetascience Observatory
▶
Functional Interaction Between SNPs and Microsatellite in the Transcriptional Regulation of Insulin-Like Growth Factor 1
ReviewHolly Y. Chen et al.(2013)· Human Mutation

This comprehensive review examines the association between type 2 diabetes mellitus (T2DM) and multiple myeloma (MM) risk. Genetic variants linked to T2DM show opposite associations with MM compared to diabetes GWAS: variants like CDKN2A-2B rs2383208, IGF1 rs35767, KCNQ1 rs2237892, and MADD rs7944584 increase MM risk, while FTO rs8050136, KCNJ11 rs5215/rs5219, LTA rs1041981, and THADA rs7578597 decrease risk. The IGF1 rs35767 promoter polymorphism is strongly associated with MM risk via cell proliferation mechanisms. A meta-analysis of 20 observational studies (>3 million participants) found T2DM patients had OR=1.53 (95% CI, 1.30-1.81) for MM, and MetS patients had OR=1.39 (95% CI, 1.17-1.64), mediated through insulin resistance, hyperinsulinemia, inflammatory cytokines (IL-6, TNF-α, IL-1β), dyslipidemia, and acidosis pathways.

Traits studied:Insulin resistanceMetabolic syndromeMultiple myelomaNephropathyPeripheral neuropathyRetinopathyType 2 diabetes mellitus
PubMedDOIMetascience Observatory
▶
Genetic variation within the NR1H2 gene encoding liver X receptor β associates with insulin secretion in subjects at increased risk for type 2 diabetes
AssociationN=1,574Caroline Ketterer et al.(2011)· Journal of Molecular Medicine

In 1,574 subjects of European ancestry at high risk for type 2 diabetes, genetic variation in the NR1H2 gene (encoding liver X receptor β) was associated with impaired insulin secretion. The SNP rs2248949 showed significant association with insulin secretion during IVGTT (p=0.007) in a dominant model, with minor allele carriers showing 26% reduced insulin secretion. NR1H2 rs1405655 was also associated with first-phase insulin secretion (p=0.003), and NR1H3 rs11039149 associated with proinsulin conversion to insulin.

Traits studied:Fasting glucoseFirst-phase insulin secretionInsulin secretionInsulin sensitivityProinsulin conversionType 2 diabetes
PubMedDOIMetascience Observatory

About MADD

Tumor necrosis factor alpha (TNF-alpha) is a signaling molecule that interacts with one of two receptors on cells targeted for apoptosis. The apoptotic signal is transduced inside these cells by cytoplasmic adaptor proteins. The protein encoded by this gene is a death domain-containing adaptor protein that interacts with the death domain of TNF-alpha receptor 1 to activate mitogen-activated protein kinase (MAPK) and propagate the apoptotic signal. It is membrane-bound and expressed at a higher level in neoplastic cells than in normal cells. Several transcript variants encoding different isoforms have been described for this gene. [provided by RefSeq, Jul 2008]

View all MADD variants →

Gene information from NCBI Gene. Variant classifications from ClinVar.

Community Wiki

No community notes yet for this variant. Sign in to start one.

Comments

Sign in to join the discussion.

Loading comments…