NM_000176.2(NR3C1):c.66G>A (p.Glu22=) AND Glucocorticoid resistance, relative

Clinical significance:Pathogenic (Last evaluated: Dec 1, 2007)

Review status:(0/4) 0 stars out of maximum of 4 stars

no assertion criteria provided

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000017536.30

Allele description

NM_000176.2(NR3C1):c.66G>A (p.Glu22=)

Gene:
NR3C1:nuclear receptor subfamily 3 group C member 1 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
5q31.3
Genomic location:
Preferred name:
NM_000176.2(NR3C1):c.66G>A (p.Glu22=)
HGVS:
  • NC_000005.10:g.143400774C>T
  • NG_009062.1:g.39739G>A
  • NM_000176.2:c.66G>A
  • NM_001018077.1:c.66G>A
  • NM_001204258.1:c.-13G>A
  • NP_000167.1:p.Glu22=
  • NP_001018087.1:p.Glu22=
  • NC_000005.9:g.142780339C>T
Links:
OMIM: 138040.0011; dbSNP: rs6189
GMAF:
0.0106(T), 6189
NCBI 1000 Genomes Browser:
rs6189
Molecular consequence:
  • NM_001204258.1:c.-13G>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001018077.1:c.66G>A - synonymous variant - [Sequence Ontology: SO:0001819]

Condition(s)

Name:
Glucocorticoid resistance, relative
Identifiers:
MedGen: C4016115

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000037808OMIMno assertion criteria providedPathogenic
(Dec 1, 2007)
germlineliterature only

PubMed (6)
[See all records that cite these PMIDs]

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlinenot providednot providednot providednot providednot providednot providedliterature only

Citations

PubMed

Lack of association between five polymorphisms in the human glucocorticoid receptor gene and glucocorticoid resistance.

Koper JW, Stolk RP, de Lange P, Huizenga NA, Molijn GJ, Pols HA, Grobbee DE, Karl M, de Jong FH, Brinkmann AO, Lamberts SW.

Hum Genet. 1997 May;99(5):663-8.

PubMed [citation]
PMID:
9150737

A polymorphism in the glucocorticoid receptor gene, which decreases sensitivity to glucocorticoids in vivo, is associated with low insulin and cholesterol levels.

van Rossum EF, Koper JW, Huizenga NA, Uitterlinden AG, Janssen JA, Brinkmann AO, Grobbee DE, de Jong FH, van Duyn CM, Pols HA, Lamberts SW.

Diabetes. 2002 Oct;51(10):3128-34.

PubMed [citation]
PMID:
12351458
See all PubMed Citations (6)

Details of each submission

From OMIM, SCV000037808.4

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedliterature only PubMed (6)

Description

Koper et al. (1997) identified a polymorphism consisting of 2 linked point mutations in the glucocorticoid receptor gene. The first mutation, a G-to-A transition in codon 22, is silent, with both GAG and GAA coding for glutamic acid (E). The second mutation changes codon 23 from arginine (R) to lysine (K) (AGG-AAG). Van Rossum et al. (2002) found an association of this polymorphism with relative resistance to glucocorticoids (GCCR; 615962), and in a population-based study in the elderly observed that carriers of the 22/23EK (ER22/23EK) polymorphism had better insulin sensitivity and lower total and low density lipoprotein cholesterol levels. They also found the frequency of the ER22/23EK allele to be higher in the elder half of the studied population, which suggested a survival advantage. In a separate population of 402 elderly Dutch men, van Rossum et al. (2004) found that after 4 years of follow-up 19.2% of the noncarriers had died, whereas none of the 21 ER22/23EK carriers had died. ER22/23EK carriers also had lower serum C-reactive protein (123260) levels, possibly reflecting improved cardiovascular status.

Van Rossum et al. (2004) investigated the association of the ER22/23EK polymorphism with differences in body composition and muscle strength in a cohort of 350 subjects who were followed from age 13 to 36 years. They identified 27 (8%) heterozygous ER22/23EK carriers. In males at 36 years of age, they found that ER22/23EK carriers were taller, had more lean body mass, greater thigh circumference, and more muscle strength in arms and legs. They observed no differences in body mass index or fat mass. In females, waist and hip circumferences tended to be smaller in ER22/23EK carriers at the age of 36 years, but no differences in body mass index were found. The authors concluded that the ER22/23EK polymorphism is associated with a sex-specific, beneficial body composition at young adult age, as well as greater muscle strength in males.

Russcher et al. (2005) examined the effects of the ER22/23EK polymorphism on glucocorticoid sensitivity at the level of gene expression in functional assays. The ER22/23EK polymorphism produced a significant reduction of transactivating capacity in both transfection experiments and in peripheral blood mononuclear lymphocytes of carriers of this polymorphism. The ER22/23EK polymorphism did not seem to influence the transrepressing capacity of the glucocorticoid receptor.

Finken et al. (2007) tested the effects of the R23K (ER22/23EK) and N363S (138040.0007) polymorphisms in the GCCR gene, associated with decreased and increased sensitivity to cortisol, respectively, on linear growth and the adult metabolic profile in a cohort of 249 men and women born less than 32 weeks' gestation and followed up prospectively from birth until 19 years of age. The 23K variant, present in 24 individuals, was associated with lower fasting insulin levels and a lower homeostatic model assessment for insulin resistance index, as well as with a taller stature from the age of 1 year. Carriers of the 23K variant showed complete catch-up growth between the ages of 3 months and 1 year, and attained height was similar to the population reference mean, whereas stature in noncarriers was on average 0.5 standard deviation below this mean. Finken et al. (2007) concluded that carriers of the 23K variant are, at least in part, protected against postnatal growth failure and insulin resistance after preterm birth.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlinenot providednot providednot providednot providednot providednot providednot providednot provided

Last Updated: Oct 3, 2016

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