A G468-T AMPD1 mutant allele contributes to the high incidence of myoadenylate deaminase deficiency in the Caucasian population

Gross, Manfred; Rötzer, E.; Kölle, Petra; Mortier, W.; Reichmann, Heinz; Goebel, Hans‐Hilmar; Lochmüller, Hanns; Pongratz, D.; Mahnke-Zizelman, Donna K.; Sabina, Richard L.

doi:10.1016/s0960-8966(02)00008-1

Cited by 31 publications

(30 citation statements)

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“…We selected six variants (rs926938, rs2010899, rs2268698, rs2269697, rs743041, and rs761755) based on the finding that they were commonly shared across different population groups (11). We also genotyped missense variants known to be associated with altered AMPD1 function (Q12X, P48L, and Q156H) (12,13). The remaining variants were selected from the National Center for Biotechnology Information SNP database (www.ncbi.nlm.nih.gov/SNP/).…”

Section: Methodsmentioning

confidence: 99%

Variation in the Gene for Muscle-Specific AMP Deaminase Is Associated With Insulin Clearance, a Highly Heritable Trait

et al. 2005

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The rising prevalence of the insulin resistance syndrome in our society necessitates a better understanding of the genetic determinants of all aspects of insulin action and metabolism. We evaluated the heritability of insulin sensitivity and the metabolic clearance rate of insulin (MCRI) as quantified by the euglycemic-hyperinsulinemic clamp in 403 Mexican Americans. We tested the candidate gene AMP deaminase 1 (AMPD1) for association with insulin-related traits because it codes for an enzyme that has the potential to influence multiple aspects of insulin pharmacodynamics. By converting AMP to inosine monophosphate, AMPD1 plays a major role in regulating cellular AMP levels; AMP activates AMP kinase, an enzyme that modulates cellular energy and insulin action. We determined that nine AMPD1 single nucleotide polymorphisms (SNPs) defined two haplotype blocks. Insulin clearance was found to have a higher heritability (h 2 ‫؍‬ 0.58) than fasting insulin (h 2 ‫؍‬ 0.38) or insulin sensitivity (h 2 ‫؍‬ 0.44). The MCRI was associated with AMPD1 SNPs and haplotypes. Insulin clearance is a highly heritable trait, and specific haplotypes within the AMPD1 gene, which encodes a skeletal muscle؊specific protein, are associated with variation in insulin clearance. We postulated that the processes of insulin action and insulin clearance in skeletal muscle are highly regulated and that AMPD1 function may play an important role in these phenomena. Diabetes 54: 1222-1227, 2005 T he insulin resistance syndrome (also called the metabolic syndrome) is a clustering of factors associated with an increased risk of coronary artery disease (1). In the U.S., Ͼ20% of adults are affected by it (2). Mexican Americans have a high prevalence of hyperinsulinemia and insulin resistance as well as the highest age-specific prevalence of the insulin resistance syndrome (2-4). Thus, by studying a large familybased sample of Mexican-American subjects, we sought to elucidate the genetic determinants of insulin metabolism and action.In pursuit of this goal, we evaluated insulin phenotypes using the euglycemic-hyperinsulinemic clamp study. Assessment of the glucose infusion rate (M) during the euglycemic-hyperinsulinemic clamp is regarded as the most direct physiological measurement of insulin sensitivity (5,6). The clamp also allows calculation of the metabolic clearance rate of insulin (MCRI). In this family-based study, we assessed the variation of these traits within families and observed for the first time a high heritability for MCRI. To begin to identify specific genes that mediate heritability of insulin-related phenotypes, we selected a candidate gene, AMP deaminase 1 (AMPD1), which has been shown to influence skeletal muscle adenine nucleotide levels (7) and which in turn could have effects on other enzymes, such as AMP-activated protein kinase (AMPK), that are known to influence insulin action (8). We show herein that polymorphisms in AMPD1 are associated with variation in the MCRI. RESEARCH DESIGN AND METHODSThe University of California at Lo...

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Section: Methodsmentioning

confidence: 99%

Variation in the Gene for Muscle-Specific AMP Deaminase Is Associated With Insulin Clearance, a Highly Heritable Trait

et al. 2005

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“…Several previous studies reported that the porcine AMPD1 maps within a known quantitative trait locus with effects on carcass traits such as carcass weight, loin and neck meat weight, loin muscle area, shoulder meat weight, ham meat weight, and chop weight (Geldermann et al, 1999;Walling et al, 2000;Cepica et al, 2003). A new mutation was found in exon 5 (G468T); the G468T transversion is dysfunctional and further indicates that AMPD1 alleles harboring this mutation contribute to the high incidence of partial and complete myoadenylate deaminase deficiency in the Caucasian population (Gross et al, 2002). In cattle, the association between the 18-bp deletion mutation in the AMPD1 gene and body measurement and carcass traits of Qinchuan cattle were analyzed, and the cattle with the AA genotype (wild-type) had slaughter weight and carcass weight greater than those with genotype AB (P < 0.01 or P < 0.05) (He et al, 2010).…”

Section: Discussionmentioning

confidence: 99%

DNA sequence polymorphism within the bovine adenosine monophosphate deaminase 1 (AMPD1) is associated with production traits in Chinese cattle

Wei

Wang²,

Chen

et al. 2015

Genet. Mol. Res.

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ABSTRACT. The objectives of the present study were to detect an 18-bp deletion mutation in the bovine adenosine monophosphate deaminase 1 (AMPD1) gene and analyze its effect on growth traits in 2 Chinese cattle breeds using DNA sequencing and agarose electrophoresis. The five 19-bp polymerase chain reaction products of the AMPD1 gene exhibited 3 genotypes and 2 alleles: WW: homozygote genotype (wild-type); DD: homozygote genotype (mutant-type); WD: heterozygote genotype. Frequencies of the W allele varied from 66.15- 70.35%. The associations between the 18-bp deletion mutation in the AMPD1 gene with production traits in 226 Jia-Xian red cattle was analyzed. The animals with genotype WW showed significantly higher heart girth and body weight than those with genotypes WD and DD at 24 months (P < 0.01). Our results indicate that the deletion mutation in the AMPD1 gene is associated with production traits, and may be used for marker-assisted selection in beef cattle breeding programs.

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“…In patients heterozygous for the c.34C > T mutation other mutations such as c.1162C > T and c.1274G > A [15], c.468C > T [16], c.860A > T and c.930G > T [6] and IVS2-(4-7)delCTTT [17] might contribute to a further reduction of AMPD activity. Heterozygotes for c.34C > T and c.468G > T exhibited AMPD activities typical for TT [16].…”

Section: Discussionmentioning

confidence: 99%

AMP deaminase deficiency in skeletal muscle is unlikely to be of clinical relevance

2008

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A G468-T AMPD1 mutant allele contributes to the high incidence of myoadenylate deaminase deficiency in the Caucasian population

Cited by 31 publications

References 28 publications

Variation in the Gene for Muscle-Specific AMP Deaminase Is Associated With Insulin Clearance, a Highly Heritable Trait

Variation in the Gene for Muscle-Specific AMP Deaminase Is Associated With Insulin Clearance, a Highly Heritable Trait

DNA sequence polymorphism within the bovine adenosine monophosphate deaminase 1 (AMPD1) is associated with production traits in Chinese cattle

AMP deaminase deficiency in skeletal muscle is unlikely to be of clinical relevance

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