Diabetes
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow Purchase Article
Right arrow View Shopping Cart
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow Request Permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Siddiq, A.
Right arrow Articles by Gibson, F.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Siddiq, A.
Right arrow Articles by Gibson, F.
Social Bookmarking
Add to CiteULike   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati  
What's this?

Diabetes 54:2477-2481, 2005
© 2005 by the American Diabetes Association, Inc.

Brief Genetics Reports

A Synonymous Coding Polymorphism in the {alpha}2-Heremans-Schmid Glycoprotein Gene Is Associated With Type 2 Diabetes in French Caucasians

Afshan Siddiq1, Frederic Lepretre1,2, Serge Hercberg3, Philippe Froguel1,2, and Fernando Gibson1

1 Section of Genomic Medicine, Imperial College, Hammersmith Campus, London, United Kingdom
2 Institut de Biologie de Lille, Institut Pasteur, CHU, Lille, France
3 U557 INSERM and Unite de Surveillance et d’Epidemiologie Nutritionnelle, InVS/CNAM, Institut Scientifique et Technique de la Nutrition et de l’Alimentation/CNAM, Paris, France


   ABSTRACT
TOP
 ABSTRACT
RESEARCH DESIGN AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
{alpha}2-Heremans-Schmid glycoprotein (AHSG) is an abundant plasma protein synthesized predominantly in the liver. The AHSG gene, consisting of seven exons and spanning 8.2 kb of genomic DNA, is located at chromosome 3q27, a susceptibility locus for type 2 diabetes and the metabolic syndrome. AHSG is a natural inhibitor of the insulin receptor tyrosine kinase, and AHSG-null mice exhibit significantly enhanced insulin sensitivity. These observations suggested that the AHSG gene is a strong positional and biological candidate for type 2 diabetes susceptibility. Direct sequencing of the AHSG promoter region and exons identified nine common single nucleotide polymorphisms (SNPs) with a minor allele frequency ≥5%. We carried out a detailed genetic association study of the contribution of these common AHSG SNPs to genetic susceptibility of type 2 diabetes in French Caucasians. The major allele of a synonymous coding SNP in exon 7 (rs1071592) presented significant evidence of association with type 2 diabetes (P = 0.008, odds ratio 1.27 [95% CI 1.06–1.52]). Two other SNPs (rs2248690 and rs4918) in strong linkage disequilibrium with rs1071592 showed evidence approaching significance. A haplotype carrying the minor allele of SNP rs1071592 was protective against type 2 diabetes (P = 0.014). However, our analyses indicated that rs1071592 is not associated with the evidence for linkage of type 2 diabetes to 3q27.

Address correspondence and reprint requests to Fernando Gibson, Section of Genomic Medicine, 2nd Floor, 233 L Block, Imperial College, Hammersmith Campus, Du Cane Rd., London, W12 0NN U.K. E-mail: fernando.gibson{at}imperial.ac.uk

Abbreviations: AHSG, {alpha}2-Heremans-Schmid glycoprotein; ASP, affected sibpair; IBD, identical by descent; SNP, single nucleotide polymorphism; UTR, untranslated region

{alpha}2-Heremans-Schmid glycoprotein (AHSG) is an abundant 49-kDa plasma protein synthesized predominantly in the liver (1). The AHSG gene is located at chromosome 3q27, a susceptibility locus for type 2 diabetes and the metabolic syndrome (2–4). Originally described as the major globulin in FCS (5), AHSG is also known as fetuin-A to distinguish it from the product of the adjacent paralogous gene, FETUB (fetuin-B).

AHSG is a multifunctional protein with diverse biological functions that include the regulation of calcium homeostasis (6,7). A possible role for AHSG in influencing genetic susceptibility to type 2 diabetes was first suggested by in vitro work demonstrating that AHSG inhibits, in a dose-dependent manner, the insulin-stimulated tyrosine kinase activity of the insulin receptor, insulin receptor autophosphorylation, and insulin substrate 1 phosphorylation (1,8). These effects were corroborated in vivo in rat liver and skeletal muscle following acute injection of human recombinant AHSG (9). AHSG-null mice exhibit significantly enhanced insulin sensitivity and are resistant to weight gain on a high-fat diet (10). In humans, serum AHSG levels have been reported to be significantly higher in patients with gestational diabetes than in healthy pregnant women and to be correlated with indirect measures of insulin resistance (11). A single nucleotide polymorphism (SNP) in the promoter region of AHSG was recently associated with insulin-mediated inhibition of lipolysis and stimulation of lipogenesis in adipocytes (12). These observations indicated that AHSG may play a physiological role in the regulation of insulin signaling and energy homeostasis. Taking into consideration its location at the 3q27 type 2 diabetes susceptibility locus, the AHSG gene suggested itself as a strong positional and biological candidate gene for type 2 diabetes susceptibility. Therefore, we have evaluated the contribution of common SNPs in the AHSG gene to type 2 diabetes susceptibility in the French Caucasian population.


   RESEARCH DESIGN AND METHODS
TOP
 ABSTRACT
 RESEARCH DESIGN AND METHODS
RESULTS
 DISCUSSION
 REFERENCES
 
American Diabetes Association 2003 criteria (13) for the classification of subjects as diabetic or normoglycemic were applied. The subset of 55 French families with early-onset type 2 diabetes (age at diagnosis <46 years) that produced the linkage result at chromosome 3q27 was described previously (3). The type 2 diabetes case-control study was carried out with a cohort of 682 unrelated type 2 diabetic subjects (age 60 ± 12 years, BMI 27.0 ± 3.5 kg/m2, men/women 55/45%) and 918 unrelated normoglycemic subjects (age 54 ± 11 years, BMI 24.6 ± 3.9 kg/m2, men/women, 41/59%). The type 2 diabetic cases were composed of 310 probands from type 2 diabetic families, recruited by P. Froguel’s CNRS Institute Pasteur Unit in Lille, and 372 singleton patients with a family history of type 2 diabetes recruited at the Endocrinology-Diabetology Department of the Corbeil-Essonne Hospital. The control subjects were composed of 372 normoglycemic husbands or wives from type 2 diabetic families, and 560 normoglycemic subjects from the SUVIMAX prospective population-based cohort study (14). The morbidly obese case-control study was carried out with a cohort of 575 unrelated morbidly obese patients (age 46 ± 12 years, BMI 47.3 ± 7.4 kg/m2, men/women 23/77%) (15) using the same control subjects as for the type 2 diabetes case-control study. Subjects were all of French Caucasian ancestry. With the exception of plasma insulin levels, a number of quantitative clinical phenotypes (including plasma levels of glucose, triglycerides, and cholesterol) were assayed in >95% of our normoglycemic cohort. Plasma insulin levels were only available for the 372 normoglycemic husbands or wives. The homeostasis model assessment of insulin resistance (HOMA-IR) index was calculated as fasting insulin (µU/ml) x fasting glucose (mmol/l)/22.5 (16). Informed consent was obtained from all subjects, and the study was approved by the local ethics committees.

Screening the AHSG gene for SNPs.
We carried out SNP detection by PCR followed by direct sequencing of the PCR products. PCR primer sequences are available on request. Genomic DNA sequence spanning the AHSG gene was obtained from the National Center for Biotechnology Information (NCBI) website (available from http://www.ncbi.nlm.nih.gov/; Entrez GeneID, 197). PCRs were performed with 100 ng human genomic DNA and Taq Gold polymerase (Applied Biosystems, Foster City, CA) using standard PCR conditions in a total volume of 25 µl. Sequencing reactions were performed with the BigDye Terminator v.3 cycle sequencing kit (Applied Biosystems) and electrophoresed on the Applied Biosystems 3700 Genetic Analyzer according to the manufacturer’s instructions. Sequence analysis and SNP identification were carried out using the Phred/Phrap/Consed system (17,18). We sequenced ~1 kb upstream of the ATG codon, each exon together with ~200 bp flanking intronic sequence and 500 bp of the 3' untranslated region (UTR) in 24 unrelated probands (48 chromosomes) taken from the 24 type 2 diabetic families with the strongest evidence of linkage at 3q27 (a nonparametric linkage score ≥0.816). SNPs identified in two or less heterozygote subjects of 24 (allele frequency ≤4%) were designated rare SNPs.

SNP genotyping.
Genotyping was performed with the Sequenom MassARRAY system, as previously described (19).

Statistical analyses.
Comparisons of SNP allele and haplotype frequencies in case and control groups were performed using the {chi}2 test, with P values presented uncorrected for multiple testing. The SNPspD method (20) for correction of multiple SNP testing was employed. The basis of this method is the use of spectral decomposition of matrices of pairwise SNP linkage disequilibrium to generate an adjusted significance threshold. Testing SNP alleles for association with quantitative traits was carried out with the Wilcoxon–Kruskal-Wallis. Pairwise SNP linkage disequilibrium was calculated with the GOLD software package (21) from the haplotype counts output by PHASE (22). The Haplotype Trend Regression program (23) was used to test inferred haplotypes for association with quantitative phenotypes. Associations with the evidence for linkage analyses were carried out as described previously (24). Briefly, this involved comparing the expected and observed allele-sharing proportions for affected sibpairs (ASPs) with concordant 1/x–1/x genotypes, where one is the major allele and x is either the major or minor allele, conditional on the identical-by-descent (IBD) allele-sharing distribution of the original genome scan dataset (3).


   RESULTS
TOP
 ABSTRACT
 RESEARCH DESIGN AND METHODS
 RESULTS
DISCUSSION
 REFERENCES
 
The AHSG gene, consisting of seven exons and spanning 8.2 kb of genomic DNA, was screened for SNPs by direct sequencing. We identified nine common SNPs within the AHSG gene with a minor allele frequency ≥5% and six rare SNPs (Table 1). The same common SNPs were identified in a recent study of the effect of AHSG gene variation on obesity and insulin action in the Swedish population (12). Since the aim of this study was to evaluate common variation in the AHSG gene, the rare SNPs were not subjected to any further analysis. In addition, no further analysis was carried out on SNP rs4831 due to failure to successfully genotype it using either the Sequenom (19) or Taqman methods (25).


View this table:
[in this window]
[in a new window]

  		TABLE 1 Position of SNPs in the human AHSG gene

 
The other eight common AHSG SNPs were genotyped in our type 2 diabetic case-control cohort with an average success rate of 88%. The genotype distribution was in accordance with Hardy-Weinberg equilibrium for all SNPs (data not shown). We first evaluated the extent of pairwise linkage disequilibrium, as quantified by the metrics D' and {Delta}2 (Fig. 1). The average D' and {Delta}2 values across the AHSG gene were 0.92 and 0.28, respectively. SNPs rs4917 and rs4918 exhibited almost complete linkage disequilibrium ({Delta}2 = 0.95), whereas SNPs rs2248690 and rs1071592, at opposite ends of the gene, were also in strong linkage disequilibrium ({Delta}2 = 0.86). The results of evaluating each of the common SNPs for association with type 2 diabetes are presented in Table 2. The major allele of SNP rs1071592, a synonymous SNP in exon 7, presented evidence of association with type 2 diabetes (P = 0.008, odds ration [OR] 1.27 [95% CI 1.06–1.52]). We also observed borderline association for SNPs rs2248690 (P = 0.06) and rs4918 (P = 0.09). These results are consistent with the high level of linkage disequilibrium between these three SNPs, as measured by {Delta}2. Note that P values are presented uncorrected for multiple testing. Using the SNPSpD correction method of Nyholt (20), which accounts for intermarker linkage disequilibrium, a significance threshold of 0.009 was obtained for the eight AHSG SNPs tested. The rs1071592 association result fell just under this threshold.


Figure 1
View larger version (19K):
[in this window]
[in a new window]

  		FIG. 1. Pairwise linkage disequilibrium measures for common SNPs spanning the AHSG gene. Pairwise linkage disequilibrium was calculated with the GOLD software package (21) from the combined haplotype counts of the type 2 diabetic case and normoglycemic control subjects output by PHASE (22). P values were all <0.001.

 

View this table:
[in this window]
[in a new window]

  		TABLE 2 AHSG SNP allele frequencies in type 2 diabetic case and normoglycemic control subjects

 
SNP rs1071592 was evaluated for association with the evidence for linkage of type 2 diabetes to 3q27, using the linkage partitioning method described previously (24). We found that the observed IBD-sharing proportion of concordant-genotype ASPs carrying the major allele was no higher than that expected under the null hypothesis of no association with the evidence for linkage. The observed IBD-sharing proportion was 0.69 (from a total of 72 ASPs), whereas the expected IBD-sharing proportion for an allele with a frequency equal to that of the major allele of SNP rs1071592 was 0.75 (a total of 69 ASPs). This result argued against the hypothesis that SNP rs1071592 is significantly associated with the evidence for linkage and was corroborated using a simulation-based approach (15) (data not shown).

There were no significant differences in SNP allele or haplotype frequencies between males and females, and no additional type 2 diabetes associations were uncovered by stratifying for sex (data not shown). None of the AHSG SNPs were associated with BMI, HOMA-IR, or with plasma levels of glucose, triglycerides, or cholesterol in our nondiabetic cohort (data not shown).

The AHSG haplotype frequency distribution of type 2 diabetic case and control subjects is shown in Table 3. A total of six common AHSG haplotypes were identified, accounting for 95% of control chromosomes. The average probability of the most likely haplotype pair across the dataset was 0.95 ± 0.13. Haplotype 21122221 was associated with normoglycemia (P = 0.014), indicating a protective effect against type 2 diabetes. This finding is consistent with the SNP association results, since this haplotype is the only one carrying the minor (protective) allele of SNP rs1071592.


View this table:
[in this window]
[in a new window]

  		TABLE 3 AHSG haplotype distribution in type 2 diabetic case and normoglycemic control subjects

 
The observation that AHSG-null mice are resistant to diet-induced obesity (10) prompted us to examine a possible role for AHSG gene variation in susceptibility to human obesity. An obesity case-control study was carried out in which we genotyped AHSG SNPs in 575 morbidly obese (BMI >40 kg/m2) subjects, using the previously genotyped normoglycemic control subjects as the control set. However, we found no evidence for association of AHSG SNPs or haplotypes with morbid obesity (data not shown).


   DISCUSSION
TOP
 ABSTRACT
 RESEARCH DESIGN AND METHODS
 RESULTS
 DISCUSSION
REFERENCES
 
Significant evidence of association with type 2 diabetes was observed for a synonymous coding SNP rs1071592 in exon 7. The data presented here suggests that rs1071592 is a novel candidate polymorphism for modulating susceptibility to type 2 diabetes. However, additional large-scale case-control studies are clearly warranted to confirm the involvement of this variant in the genetic basis of type 2 diabetes susceptibility. This is especially true given that the rs1071592 association result fell just under the significance threshold after accounting for multiple testing.

SNP screening was only carried out in and around the exons and promoter region; therefore, we cannot rule out the possibility that other unassayed type 2 diabetes susceptibility SNPs exist within as yet unidentified regulatory regions within the AHSG gene. With the aim of identifying additional regulatory regions, we examined the human-mouse comparative genomic sequence of the AHSG gene together with 10 kb of flanking sequence on the VISTA website (available from http://pipeline.lbl.gov/cgi-bin/gateway2). Apart from two regions showing ≥70 conservation identities (in the promoter and proximal intron six regions) that were actually included within the sequences screened for SNPs, no other conserved regions were identified.

Although AHSG has been shown to inhibit the activity of the insulin receptor (1,8,9) we failed to find an association between AHSG SNPs and HOMA-IR. However, the number of normoglycemic subjects with fasting insulin levels (n = 372) provided only modest statistical power to detect an association of moderate effect. We also found no evidence for association of rs2077119 with type 2 diabetes, a promoter SNP that had previously been associated with insulin-mediated lipid metabolism in adipocytes (12).

Finally, we found no evidence that SNP rs1071592 is associated with the evidence for linkage of type 2 diabetes to 3q27, indicating that an as yet unidentified gene or genes at 3q27 is responsible for the linkage signal. Our efforts aimed at identifying the "causative" type 2 diabetes gene at 3q27 are ongoing.


   ACKNOWLEDGMENTS
 
This work is supported by a Wellcome Trust University Award to F.G. (no. GR065414MF), and grants from Diabetes UK (BDA no. RD01/0002308), the Association Française des Diabétologues de Langue Française (ALFEDIAM), the EU-funded GIFT Grant, the Direction de la Recherche Clinique/Assistance Publique-Hopitaux de Paris, and the program Hospitalier de Recherche Clinique (AOM 96088).

We thank Stephan Lobbens for his technical expertise and Andrew Walley and two anonymous referees for critically appraising draft versions of the manuscript.

Received for publication March 3, 2005 and accepted in revised form May 4, 2005


   REFERENCES
TOP
 ABSTRACT
 RESEARCH DESIGN AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 

  1. Auberger P, Falquerho L, Contreres JO, Pages G, Le Cam G, Rossi B, Le Cam A: Characterization of a natural inhibitor of the insulin receptor tyrosine kinase: cDNA cloning, purification, and anti-mitogenic activity. Cell 58:631–640, 1989[Medline]
  2. Kissebah AH, Sonnenberg GE, Myklebust J, Goldstein M, Broman K, James RG, Marks JA, Krakower GR, Jacob HJ, Weber J, Martin L, Blangero J, Comuzzie AG: Quantitative trait loci on chromosomes 3 and 17 influence phenotypes of the metabolic syndrome. Proc Natl Acad Sci U S A 97:14478–14483, 2000[Abstract/Free Full Text]
  3. Vionnet N, Hani El H, Dupont S, Gallina S, Francke S, Dotte S, De Matos F, Durand E, Lepretre F, Lecoeur C, Gallina P, Zekiri L, Dina C, Froguel P: Genomewide search for type 2 diabetes-susceptibility genes in French whites: evidence for a novel susceptibility locus for early-onset diabetes on chromosome 3q27-qter and independent replication of a type 2-diabetes locus on chromosome 1q21–q24. Am J Hum Genet 67:1470–1480, 2000[Medline]
  4. Francke S, Manraj M, Lacquemant C, Lecoeur C, Lepretre F, Passa P, Hebe A, Corset L, Yan SL, Lahmidi S, Jankee S, Gunness TK, Ramjuttun US, Balgobin V, Dina C, Froguel P: A genome-wide scan for coronary heart disease suggests in Indo-Mauritians a susceptibility locus on chromosome 16p13 and replicates linkage with the metabolic syndrome on 3q27. Hum Mol Genet 10:2751–2765, 2001[Abstract/Free Full Text]
  5. Pedersen KO: Fetuin: a new globin isolated from serum. Nature 154:575, 1944
  6. Wang H, Zhang M, Soda K, Sama A, Tracey KJ: Fetuin protects the fetus from TNF (Letter). Lancet 350:861–862, 1997[Medline]
  7. Schafer C, Heiss A, Schwarz A, Westenfeld R, Ketteler M, Floege J, Muller-Esterl W, Schinke T, Jahnen-Dechent W: The serum protein alpha 2-Heremans-Schmid glycoprotein/fetuin-A is a systemically acting inhibitor of ectopic calcification. J Clin Invest 112:357–366, 2003[Medline]
  8. Srinivas PR, Wagner AS, Reddy LV, Deutsch DD, Leon MA, Goustin AS, Grunberger G: Serum alpha 2-HS-glycoprotein is an inhibitor of the human insulin receptor at the tyrosine kinase level. Mol Endocrinol 7:1445–1455, 1993[Abstract]
  9. Mathews ST, Chellam N, Srinivas PR, Cintron VJ, Leon MA, Goustin AS, Grunberger G: Alpha2-HSG: a specific inhibitor of insulin receptor autophosphorylation, interacts with the insulin receptor. Mol Cell Endocrinol 164:87–98, 2000[Medline]
  10. Mathews ST, Singh GP, Ranalletta M, Cintron VJ, Qiang X, Goustin AS, Jen KL, Charron MJ, Jahnen-Dechent W, Grunberger G: Improved insulin sensitivity and resistance to weight gain in mice null for the Ahsg gene. Diabetes 51:2450–2458, 2002[Abstract/Free Full Text]
  11. Kalabay L, Cseh K, Pajor A, Baranyi E, Csakany GM, Melczer Z, Speer G, Kovacs M, Siller G, Karadi I, Winkler G: Correlation of maternal serum fetuin/alpha2-HS-glycoprotein concentration with maternal insulin resistance and anthropometric parameters of neonates in normal pregnancy and gestational diabetes. Eur J Endocrinol 147:243–248, 2002[Abstract]
  12. Dahlman I, Eriksson P, Kaaman M, Jiao H, Lindgren CM, Kere J, Arner P: alpha(2)-Heremans-Schmid glycoprotein gene polymorphisms are associated with adipocyte insulin action. Diabetologia 47:1974–1979, 2004[Medline]
  13. Expert Committee on the Diagnosis and Classification of Diabetes Mellitus: Report of the Expert Committee on the Diagnosis and Classification of Diabetes Mellitus. Diabetes Care 26 (Suppl. 1):S5–S20, 2003
  14. Hercberg S, Preziosi P, Briancon S, Galan P, Triol I, Malvy D, Roussel AM, Favier A: A primary prevention trial using nutritional doses of antioxidant vitamins and minerals in cardiovascular diseases and cancers in a general population: the SU.VI.MAX study: design, methods, and participant characteristics. SUpplementation en VItamines et Mineraux AntioXydants. Control Clin Trials 19:336–351, 1998[Medline]
  15. Boutin P, Dina C, Vasseur F, Dubois SS, Corset L, Seron K, Bekris L, Cabellon J, Neve B, Vasseur-Delannoy V, Chikri M, Charles MA, Clement K, Lernmark A, Froguel P: GAD2 on chromosome 10p12 is a candidate gene for human obesity. PLoS Biol 1:E68, 2003[Medline]
  16. Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC: Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia 28:412–419, 1985[Medline]
  17. Ewing B, Hillier L, Wendl MC, Green P: Base-calling of automated sequencer traces using phred. I. Accuracy assessment. Genome Res 8:175–185, 1998[Abstract/Free Full Text]
  18. Gordon D, Abajian C, Green P: Consed: a graphical tool for sequence finishing. Genome Res 8:195–202, 1998[Abstract/Free Full Text]
  19. Jurinke C, van den Boom D, Cantor CR, Koster H: Automated genotyping using the DNA MassArray technology. Methods Mol Biol 187:179–192, 2002[Medline]
  20. Nyholt DR: A simple correction for multiple testing for single-nucleotide polymorphisms in linkage disequilibrium with each other. Am J Hum Genet 74:765–769, 2004[Medline]
  21. Abecasis GR, Cookson WO: GOLD: graphical overview of linkage disequilibrium. Bioinformatics 16:182–183, 2000[Abstract/Free Full Text]
  22. Stephens M, Smith NJ, Donnelly P: A new statistical method for haplotype reconstruction from population data. Am J Hum Genet 68:978–989, 2001[Medline]
  23. Zaykin DV, Westfall PH, Young SS, Karnoub MA, Wagner MJ, Ehm MG: Testing association of statistically inferred haplotypes with discrete and continuous traits in samples of unrelated individuals. Hum Hered 53:79–91, 2002[Medline]
  24. Gibson F, Froguel P: Genetics of the APM1 locus and its contribution to type 2 diabetes susceptibility in French Caucasians. Diabetes 53:2977–2983, 2004[Abstract/Free Full Text]
  25. Livak KJ: Allelic discrimination using fluorogenic probes and the 5' nuclease assay. Genet Anal 14:143–149, 1999[Medline]

Add to CiteULike CiteULike   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati    What's this?


This article has been cited by other articles:


Home page
 DiabetesHome page
G. Andersen, K. S. Burgdorf, T. Sparso, K. Borch-Johnsen, T. Jorgensen, T. Hansen, and O. Pedersen
AHSG Tag Single Nucleotide Polymorphisms Associate With Type 2 Diabetes and Dyslipidemia: Studies of Metabolic Traits in 7,683 White Danish Subjects
Diabetes, May 1, 2008; 57(5): 1427 - 1432.
[Abstract] [Full Text] [PDF]

Home page
 J. Clin. Endocrinol. Metab.Home page
A. B. Lehtinen, K. P. Burdon, J. P. Lewis, C. D. Langefeld, J. T. Ziegler, S. S. Rich, T. C. Register, J. J. Carr, B. I. Freedman, and D. W. Bowden
Association of {alpha}2-Heremans-Schmid Glycoprotein Polymorphisms with Subclinical Atherosclerosis
J. Clin. Endocrinol. Metab., January 1, 2007; 92(1): 345 - 352.
[Abstract] [Full Text] [PDF]

Home page
 Diabetes CareHome page
N. Stefan, A. M. Hennige, H. Staiger, J. Machann, F. Schick, S. M. Krober, F. Machicao, A. Fritsche, and H.-U. Haring
{alpha}2-Heremans-Schmid Glycoprotein/ Fetuin-A Is Associated With Insulin Resistance and Fat Accumulation in the Liver in Humans
Diabetes Care, April 1, 2006; 29(4): 853 - 857.
[Abstract] [Full Text] [PDF]

Home page
 DiabetesHome page
C. Cheyssac, C. Dina, F. Lepretre, V. Vasseur-Delannoy, A. Dechaume, S. Lobbens, B. Balkau, J. Ruiz, G. Charpentier, F. Pattou, et al.
EIF4A2 Is a Positional Candidate Gene at the 3q27 Locus Linked to Type 2 Diabetes in French Families.
Diabetes, April 1, 2006; 55(4): 1171 - 1176.
[Abstract] [Full Text] [PDF]

This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow Purchase Article
Right arrow View Shopping Cart
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow Request Permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Siddiq, A.
Right arrow Articles by Gibson, F.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Siddiq, A.
Right arrow Articles by Gibson, F.
Social Bookmarking
Add to CiteULike   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati  
What's this?

HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Diabetes Diabetes Care Clinical Diabetes Diabetes Spectrum