Association of the μ-opioid receptor gene with type 2 diabetes mellitus in an African American population

Gallagher, Carla J.; Gordon, Candace J.; Langefeld, Carl D.; Mychaleckyj, Josyf C.; Freedman, Barry I.; Rich, Stephen S.; Bowden, Donald W.; Sale, Michèle M.

doi:10.1016/j.ymgme.2005.07.013

Cited by 21 publications

(21 citation statements)

References 28 publications

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“…Interestingly, RGS17 is involved in the desensitization of OPRM1 (Rodriguez-Munoz et al 2007) and, as noted, significant association in the OPRM1 gene was observed previously in our AA population (Gallagher et al 2006) and again in the current study. Interaction analyses of RGS17 SNP rs685449 and OPRM1 SNPs rs2075572 (recessive P=0.035 for the interaction term; data not shown) and rs497976 (recessive P=0.023 for interaction; data not shown), genotyped in previous analyses Gallagher et al (2006), provides some support for epistasis between these genes.…”

Section: Discussionsupporting

confidence: 88%

“…Our prior positional candidate gene studies of this region identified significant associations with T2DM for variants in ESR1 (Gallagher et al 2007a) and μ-opioid receptor (OPRM1) (Gallagher et al 2006) genes in an AA population, although these did not appear likely to account for the linkage signal. We also investigated three additional positional candidate genes under the linkage peak: the tubby superfamily proteins (TUSP), mitogen-activated protein kinase kinase kinase 4 (MAP3K4) and superoxide dismutase 2 (SOD2), however, significant associations were not observed (unpublished data).…”

Section: Introductionmentioning

confidence: 90%

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Evaluation of a SNP map of 6q24–27 confirms diabetic nephropathy loci and identifies novel associations in type 2 diabetes patients with nephropathy from an African-American population

et al. 2008

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Previously we performed a genome scan for type 2 diabetes (T2DM) using 638 African-American (AA) affected sibling pairs from 247 families; non-parametric linkage analysis suggested evidence of linkage at 6q24-27 (LOD 2.26). To comprehensively evaluate this region we performed a 2-stage association study by first constructing a SNP map of 754 SNPs selected from HapMap on the basis of linkage disequilibrium (LD) in 300 AAT2DM-ESRD subjects, 311 AA controls, 43 European American controls and 45 Yoruba Nigerian samples (Set 1). Replication analyses were conducted in an independent population of 283 AA T2DM-ESRD subjects and 282 AA controls (Set 2). In addition, we adjusted for the impact of admixture on association results by using ancestry informative markers (AIMs). In Stage 1, 137 (18.2%) SNPs showed nominal evidence of association (P<0.05) in one or more of tests of association: allelic (n=33), dominant (n=36), additive (n=29), or recessive (n=34) genotypic models, and 2-(n=47) and 3-SNP (n=43) haplotypic analyses. These SNPs were selected for follow-up genotyping. Stage 2 analyses confirmed association with a predicted 2-SNP "risk" haplotype in the PARK2 gene. Also, two intergenic SNPs showed consistent genotypic association with T2DM-ESRD: rs12197043 and rs4897081. Combined analysis of all subjects from both stages revealed nominal associations with 17 SNPs within genes; including suggestive associations in ESR1 and PARK2. This study confirms known diabetic nephropathy loci and identifies potentially novel susceptibility variants located within 6q24-27 in AA.

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Section: Discussionsupporting

confidence: 88%

Section: Introductionmentioning

confidence: 90%

Evaluation of a SNP map of 6q24–27 confirms diabetic nephropathy loci and identifies novel associations in type 2 diabetes patients with nephropathy from an African-American population

et al. 2008

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“…SNPs in the OPRM1 gene have been investigated for their involvement in various other disorders (Supplementary table 3) [33, [153][154][155][156][157][158][159][160][161][162][163][164][165][166][167][168][169][170]. The A118G SNP is the only variation that has been associated with susceptibility to disorders and related traits in numerous studies.…”

Section: Association Of Snps In the Oprm1 Gene With Other Disordersmentioning

confidence: 99%

Pharmacogenomics of the Human µ-Opioid Receptor

Kasai

Ikeda

2011

Pharmacogenomics

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The µ-opioid receptor is a primary target for clinically important opioid analgesics, including morphine, fentanyl and methadone. Many genetic variations have been identified in the human µ-opioid receptor MOP gene (OPRM1), and their implications have been reported in the effects of opioid drugs and susceptibility to drug dependence. Interestingly, agonistic and antagonistic opioid effects are inversely associated with the A118G polymorphism genotype. The A118G polymorphism may also be associated with substance dependence and susceptibility to other disorders, including epilepsy and schizophrenia. The IVS1+A21573G, IVS1-T17286C, and TAA+A5359G polymorphisms in the OPRM1 gene may be associated with alcohol, opioid and tobacco dependence, respectively. However, some studies have failed to confirm the correlations between the polymorphisms and opioid effects and substance dependence. Further studies are needed to elucidate the molecular mechanisms underlying the effects of OPRM1 polymorphisms.

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“…We recruited 380 unrelated AA individuals with T2DM and end-stage renal disease (T2DM-ESRD). The clinical characteristics and recruitment of AA patients and controls have been previously described in detail [14]. The case population was recruited independently of the families used for linkage analyses [1].…”

Section: Subjectsmentioning

confidence: 99%

Association of the proprotein convertase subtilisin/kexin-type 2 (PCSK2) gene with type 2 diabetes in an African American population

Leak

Keene

Langefeld

et al. 2007

Molecular Genetics and Metabolism

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In a genome-wide scan for type 2 diabetes (T2DM) in African American (AA) families, ordered subsets analysis (OSA) provided evidence for linkage to chromosome 20p in a subset with later age at diagnosis (max. LOD 2.57, P = 0.008). The proprotein convertase subtilisin/kexin-type 2 (PCSK2) gene is within the LOD-1 interval of this linkage peak. Twenty-nine single nucleotide polymorphisms (SNPs) were genotyped across this gene in 380 unrelated AA individuals with T2DM and end-stage renal disease (T2DM-ESRD), 278 AA controls, 96 European Americans (EA) and 120 Yoruba Nigerian (YRI) controls. In addition, 22 ancestry-informative markers (AIMs) were genotyped in all AA subjects, 120 YRI, and 96 EA controls. ADMIXMAP was used to model the distributions of admixture and generate score tests of allelic and haplotypic association. Association with T2DM was observed among 4 SNPs: rs2021785 (admixture-adjusted P a = 0.00014), rs1609659 (P a = 0.028), rs4814597 (P a = 0.039) and rs2269023 (P a = 0.043). None of the PCSK2 SNPs were associated with age at T2DM diagnosis. A variant in the PCKS2 gene, rs2021785, appears to play a role in susceptibility to T2DM in this AA population.

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Association of the μ-opioid receptor gene with type 2 diabetes mellitus in an African American population

Cited by 21 publications

References 28 publications

Evaluation of a SNP map of 6q24–27 confirms diabetic nephropathy loci and identifies novel associations in type 2 diabetes patients with nephropathy from an African-American population

Evaluation of a SNP map of 6q24–27 confirms diabetic nephropathy loci and identifies novel associations in type 2 diabetes patients with nephropathy from an African-American population

Pharmacogenomics of the Human µ-Opioid Receptor

Association of the proprotein convertase subtilisin/kexin-type 2 (PCSK2) gene with type 2 diabetes in an African American population

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