This Article Abstract Full Text (PDF) Submit a related Letter to the Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Møller, A. M. Articles by Pedersen, O. Search for Related Content PubMed PubMed Citation Articles by Møller, A. M. Articles by Pedersen, O.

Studies of Genetic Variability of the Glucose Transporter 2 Promoter in Patients with Type 2 Diabetes Mellitus

Steno Diabetes Center and Hagedorn Research Institute (A.M.M., N.M.J., J.P., K.B.-J., S.A.U., T.H., O.P.), DK-2820 Gentofte, Copenhagen, Denmark; and Centre of Preventive Medicine (T.D., K.B.-J.), Glostrup University Hospital, DK-2600 Glostrup, Denmark

Address all correspondence and requests for reprints to: Ann Merete Møller, Steno Diabetes Center, Niels Steensens Vej 2, DK-2820 Gentofte, Copenhagen, Denmark.

	Abstract

Top Abstract Introduction Materials and Methods Results Discussion References

 
This study was performed to test the hypothesis that genetic variation in the promoter of the glucose transporter 2 (GLUT2) might predispose to prediabetic phenotypes or type 2 diabetes. A total of 1611 bp comprising the minimal promoter region of the GLUT2 gene were examined by combined single-strand conformational polymorphism and heteroduplex analysis followed by direct sequencing of identified variants on genomic DNA from 96 randomly recruited Danish type 2 diabetic patients. We identified 4 nucleotide variants, -447ga, -149ca, -122tc, and -44ga. None of the variants were positioned in known or presumed transcription factor binding sites, TATA-box, or transcriptional start site. Association studies of the -149ca, -122tc, and -44ga variants revealed that the variants were as prevalent in 320 type 2 diabetic patients [11.0% (95% confidence interval, 8.4–13.6), 9.8% (7.4–12.2), and 29.0% (24.4–33.6), respectively] as in 241 age-matched glucose-tolerant subjects [13.1% (9.8–16.4), 11.2% (8.3–14.1), and 33.4% (28.8–38.0), respectively]. The -447ga mutation was only identified in a single diabetic patient and did not show cosegregation with diabetes in the family of the proband. The three common variants showed in a primary genotype-phenotype study comprising 241 glucose-tolerant middle-aged subjects association to increased plasma glucose levels during an oral glucose tolerance test. However, this result could not be replicated in a second sample of 298 60-yr-old glucose-tolerant subjects.

In conclusion, we found no evidence supporting the hypothesis that genetic variability in the minimal promoter of the GLUT2 is associated with type 2 diabetes or prediabetic phenotypes in the Danish population.

	Introduction

Top Abstract Introduction Materials and Methods Results Discussion References

 
RECENTLY, THE GENETIC cause of six subtypes of maturity-onset diabetes of the young (MODY), a form of diabetes characterized by autosomal dominant inheritance, early onset (before 25 yr of age), and a primary defect in insulin secretion, was identified (1). Five of these MODY subtypes, i.e. MODY1 and MODY3–6, are caused by mutations in the genes encoding the transcription factors hepatocyte nuclear factor (HNF)-4, HNF-1, insulin promoter factor-1, HNF-1ß, and neuronal determinator factor-1, respectively (1). Interestingly, these transcription factors interact in a complex network that is involved in the transcriptional regulation of several genes expressed in liver and pancreatic ß-cells. Among these genes is the sixth MODY gene, the glucokinase gene (MODY2), which encodes the low-affinity hexokinase that is expressed in pancreatic ß-cells and liver cells (1). Furthermore, several other genes involved in lipid and glucose metabolism, e.g. the insulin gene and the gene encoding the liver-, intestine-, and pancreas-specific glucose transporter 2 (GLUT2) have been shown to be regulated by transcription factors implicated in this network.

GLUT2 is a high-capacity, low-affinity GLUT (Km 15–20 mmol/L) that allows glucose uptake in pancreatic ß-cells and liver to be proportional to plasma glucose concentrations in the physiological range. It has been hypothesized that GLUT2 and glucokinase operate in tandem to provide islet ß-cells with a mechanism to respond to subtle changes in plasma glucose concentrations (2). And although the first phosphorylation step of glucose catalyzed by glucokinase is the rate-limiting step, glucose must be transported rapidly into the cell (3). GLUT2 and the other GLUT expressed in pancreatic ß-cells, GLUT1, are supposed to mediate this transport in humans (4). Therefore, it could be hypothesized that significant reductions in GLUT capacity, especially GLUT2 capacity, might influence glucose metabolism in pancreatic ß-cells and thereby influence insulin secretion. Furthermore, a decrease in GLUT2 expression might be predicted to mediate a reduced uptake and metabolism of glucose by the liver.

Knockout of the GLUT2 gene in mice in which GLUT2 is the primary GLUT in pancreatic ß-cells results in abnormal postnatal pancreatic ß-cell development, loss of glucoseinduced insulin secretion and early development of type 2 diabetes (5). In agreement with this finding, expression of GLUT2 antisense messenger RNA in ß-cells of transgenic mice is also associated with reduced glucose-induced insulin secretion and development of diabetes, substantiating that GLUT2 is important for glucose homeostasis in mice (6).

In humans, homozygous carriers of stop or frameshift mutations in the GLUT2 gene develop the Fanconi-Bickel syndrome, or glycogen storage disease type XI, characterized by hepatorenal glycogen accumulation, hypoglycemia, hypergalactosemia, and Fanconi nephropathy (7). It has been hypothesized that heterozygous carriers of mutations causing Fanconi-Bickel syndrome may be predisposed to type 2 diabetes (8). Accordingly, linkage studies of the chromosomal region, 3q26, encompassing the GLUT2 gene and mutational analysis of the coding region of the gene have been performed, however, without any consistent finding of linkage or association with type 2 diabetes (8, 9, 10). Although one of the identified missense mutations, Val197Ile, was only present in a single diabetic subject and has been shown in functional experiments to abolish GLUT activity implying that defects in GLUT2 may be involved in the pathogenesis of type 2 diabetes (10, 11).

In this study, we have examined the minimal promoter region of the GLUT2 gene for nucleotide variability associated with type 2 diabetes or prediabetic phenotypes.

	Materials and Methods

Top Abstract Introduction Materials and Methods Results Discussion References

 
Subjects

Mutation analysis was performed on genomic DNA from 94 type 2 diabetic patients. The subsequent association studies were performed in 320 unrelated Danish Caucasian type 2 diabetic patients recruited from the outpatient clinic at Steno Diabetes Center (Copenhagen, Denmark) and 241 age-matched, unrelated, and glucose-tolerant Danish Caucasian control subjects traced randomly in the Danish Central Population Register and living in the same area of Copenhagen as the type 2 diabetic patients. Type 2 diabetes was diagnosed by 1985 WHO criteria, and all control subjects underwent a standard oral glucose tolerance test (OGTT). The type 2 diabetic patients (140 women and 180 men) had a clinical onset of diabetes of 54.7 ± 10.6 yr (mean ± SD), an average duration of known diabetes of 6.1 ± 5.9 yr, fasting plasma glucose of 9.9 ± 3.5 mmol/L, fasting serum C-peptide of 679 ± 297 pmol/L, and hemoglobin A_1c of 8.4 ± 1.6% (interval for normal subjects, 4.1–6.4%). For genotypephenotype interaction studies plasma glucose, serum insulin, and serum C-peptide values during the OGTT of the normal glucose-tolerant subjects were examined. Positive associations between intermediary phenotypes and nucleotide variants were further evaluated in a population-based sample of 298 60-yr-old subjects, which constitutes a random subset of an age-specific cohort, also from the Copenhagen area. These subjects had also undergone a 75-g OGTT. The study protocols were approved by the Ethical Committee of Copenhagen and were in accordance with the principles of the Declaration of Helsinki II. Before the participation in the study informed consent was obtained for all studied subjects.

Biochemical variables

The plasma concentration of glucose was analyzed by an automated glucose oxidase method. The concentration of specific insulin [excluding des(31, 32) and intact proinsulin] in serum was measured by ELISA and the concentration of serum C-peptide was determined by RIA using Steno Diabetes Center routine methods. Hemoglobin A_1c was determined by high performance liquid chromatography (Variant Analyzer; Bio-Rad Laboratories, Inc. Richmond, CA).

Primary mutation analysis of the promoter region of the GLUT2 gene

The minimal promoter region (GenBank accession no. L09674) [position, -1277 to +334 bp (numbered according to transcription initiation site)] was examined in 6 segments sized 200–350 bp by combined single-strand conformational polymorphism and hetereoduplex scanning with two different experimental settings as described previously (12). The segments were amplified using specific primers as follows: segment 1: GLUT2.prom-1f, 5'-5'-tgcagaatgtcatgtcac-3', and GLUT2.prom-r1, 5'-tgtaatgcagacacaatac-3'; segment 2: GLUT2.prom-2f, 5'-tatttgctcacgcttttcc-3', and GLUT2.prom-2r, 5'-ccagcagcaacacaatgag-3'; segment 3: GLUT2.prom-3f, 5'-aatccttcattttctcacc-3', and GLUT2.prom-3r, 5'-agcggttgttattattattgc-3'; segment 4: GLUT2.prom-4f, 5'-ctacgttaaagcctccagc-3', and GLUT2.prom-4r, 5'-gctgtggtgtttctgtttag-3'; segment 5: GLUT2.prom-5f, 5'-cattcaagtcaacaatggtc-3', and GLUT2.prom-5r, 5'-gcttcaatacctttgttcc-3'; and segment 6: GLUT2.prom-6f, 5'-acttatgcctaagggacct-3', and GLUT2.prom-6r, 5'-ttgaaatgaatataatgct-3. PCR conditions were as follows: denaturation at 94 C for 3 min followed by 35 cycles of denaturation at 94 C for 30 sec; annealing at 55 C (segments 3, 5, and 6) or 60 C (segments 2 and 4) for 30 sec; and extension at 72 C for 30 sec with a final extension at 72 C for 9 min.

Variants identified by the SSCP/heteroduplex scanning were examined by direct sequencing. PCR-products used for direct sequencing were amplified using the above-mentioned primers except for the addition of a -21M13 tail at the 5'end of the forward primer and a M13 reverse tail at the 5'end of the reverse primer. The PCR products were sequenced on both strands using ABI Prism Dye Primer Cycle Sequencing Kit with Amplitaq DNA Polymerase FS and ABI prism 373 (Perkin-Elmer Corp., Foster City, CA).

Screening for identified polymorphisms in the GLUT2 promoter

PCR amplification of the DNA segments containing the -149ca, -447ga, -122tc, or -44ga polymorphisms were performed using the following conditions: forward primer 5'-aaacagaaacacagcactgat-3' and reverse primer 5'-gtggcttcaatacctttgttcc-3' [1.5 mmol/L MgCl₂ and annealing temperature (T_anneal) = 55 C], 5'-agctcaataaatttgatatccgctg-3' and 5'-aacatataataagtacttagcaaacag-3' (2.0 mmol/L MgCl₂ and T_anneal = 55 C), 5'-tcaaacccaagtccctaacaa-3'and 5'-tgcctcagcaacctgtg-3' (1.5 mmol/L MgCl₂ and T_anneal = 59 C), and 5'-tccccagtaaaatgttgag-3' and 5'-tgcctcagcaacctgtgg-3' (1.5 mmol/L MgCl₂ and T_anneal = 53 C), respectively. Restriction fragment length polymorphism was detected after a 12-h digest of PCR products with 1 U HinfI, 2 U MspAI, 1 U MnlI, and 4 U HpaII, respectively. PCR fragments were separated on 3% agarose gels and visualized by staining with ethidium bromide.

Statistics

Fisher’s exact test was applied to test for significance of differences in allele frequencies. Differences in continuous variables between carriers and noncarriers of the -122tc polymoprhism were tested using Student’s t test, whereas differences in continuous variables between wild-type, heterozygous, and homozygous carriers of the -44ga polymorphism were examined using ANOVA. Multiple regression analysis were performed on 30, 60, and 120 min and AUC_{(0–120 min)} values to adjust for confounding variables such as age, gender, and body mass index (BMI). If necessary, the variables entered in the performed analysis were logarithmically transformed. A P value less than 0.05 (two-tailed) was considered significant. Statistical Package of Social Science (SPSS) for Windows, version 9.0 (SPSS, Inc., Chicago, IL), was used for statistical analysis.

	Results

Top Abstract Introduction Materials and Methods Results Discussion References

 
SSCP-heteroduplex scanning and subsequent sequencing of the identified variants in the GLUT2 promoter in 94 type 2 diabetic patients revealed 4 nucleotide variants, -44ga, -122tc, -149ca, and -447ga numbered according to the transcriptional start site. The variants were examined in association studies consisting of 320 type 2 diabetic subjects and 241 normal glucose-tolerant control subjects; however, due to lack of PCR-product, not all individuals were genotyped. Two of the variants, -122tc and -149ca, were in strong linkage disequilibrium and had allelic frequencies of 9.8% (95% confidence interval, 7.4–12.2) and 11.0% (8.4–13.6), respectively, in type 2 diabetic patients (genotyped subjects, n = 300 and n = 284, respectively) compared with 11.2% (8.3–14.1) and 13.1% (9.8–16.4), respectively, among glucose-tolerant control subjects (n = 224 and n = 206, respectively). The -44ga polymorphism had allelic frequencies of 29.0% (24.4–33.6) in 188 type 2 diabetic patients and 33.4% (28.8–38.0) in 205 control subjects. All the allele frequencies were in Hardy-Weinberg equilibrium. None of the three polymorphisms were associated with type 2 diabetes or with significant differences in age of onset, BMI, fasting levels of plasma glucose, serum C-peptide, and serum insulin in the group of the type 2 diabetic patients (data not shown). The -447ga variant was only identified in a single diabetic subject (age at diagnosis, 59 yr of age, BMI 34 kg/m²; n = 188). Two of three offspring of the diabetic proband with the -447ga variant carried the variant. However, only one of the carriers (age at diagnosis, 40 yr, BMI 30 kg/m²) had diabetes whereas the other offspring (30 yr of age, BMI 27 kg/m²) had normal glucose tolerance according to an OGTT.

There were no differences between carriers and noncarriers of the common variants in regard to age, BMI, and fasting values of plasma glucose, serum insulin, and serum C-peptide in the control group consisting of middle-aged normal glucose-tolerant subjects (Table 1). However, heterozygous carriers of the -122tc and -149ca variants had borderline significantly or significantly increased plasma glucose levels during an OGTT compared with wild-type carriers (Table 1, only data for the -122tc variant is shown, as the two variants were in linkage disequilibrium). The two identified homozygous carriers of the two polymorphisms had even more elevated plasma glucose levels during the OGTT. Also, carriers of the -44ga variant had, despite normal serum insulin and serum C-peptide levels, borderline significantly elevated plasma glucose levels during the OGTT as measured by the incremental area under the glucose curve.

	Discussion

Top Abstract Introduction Materials and Methods Results Discussion References

Combined single-strand conformational polymorphism and heteroduplex analysis of the GLUT2 minimal promoter revealed four nucleotide variants. None of the variants were associated with type 2 diabetes per se, and although three commonly occurring variants, -122tc, -149ca, and -44ga in the primary genotype-phenotype studies showed association to decreased glucose clearance during an OGTT in glucose-tolerant subjects, this finding could not be replicated in a second sample of glucose-tolerant subjects. The power of the second genotype-phenotype study to detect a difference in the incremental area under the glucose curve similar to the difference identified in the primary study was 90%, why we consider the primary finding a spurious finding. The -447ga mutation was only identified in a single diabetic subject and did not, at the present time, show cosegregation with diabetes in the family of the proband; this is why we conclude that it is no major cause of diabetes in this family.

The pathogenic mechanism by which mutations in four transcription factors [HNF-1, HNF-1ß, HNF-4, and insulin promoting factor-1 (IPF-1)] cause the MODY form of diabetes is at present not defined. However, several knockout experiments have been performed. Knockout of the murine homologues of the IPF-1 or HNF-4 genes is embryonically lethal (13, 14), whereas postnatal inactivation of the IPF-1 gene in pancreatic ß-cells has been shown to mediate a reduced and IPF-1 dosage-dependent expression of the insulin and GLUT2 genes (15). The expression of the GLUT2 gene is also severely reduced in embryonic bodies derived from embryonic stem cells with a disrupted HNF-4 gene (16). Furthermore, transgenic mice expressing a dominant-negative form of HNF-1 (with the P291fsinsC mutation) showed remarkably decreased expression of GLUT2 (17). Taken together, these studies indicate that the GLUT2 is one of the proteins that are dysregulated in the MODY form of diabetes and opens the possibility that dysregulation of this protein might be diabetogenic. Thus, genetic variation in transcription factor binding sites (especially the binding sites for the transcription factors implicated in the pathogenesis of MODY) might have diabetogenic impact.

However, the nucleotide variation identified in this study was not positioned in any of the known binding sites for HNF-1 (nucleotide +95 to +117 and +200 to +218) (18) or in a putative IPF-1 binding site (-461–451) (19). It is at present not known whether HNF-4 binds directly to the GLUT2 promoter or mediates it impact on the GLUT2 promoter through other transcription factors and, therefore, it is also unknown whether the identified genetic variation interferes with the HNF-4 transactivation of the GLUT2 gene. Although it would be relevant to examine the combined effect of the identified promoter variants in the GLUT2 gene and known variants in the HNF-1, IPF-1, and HNF-4 genes (gene-to-gene interaction). However, given the low allelic frequencies of the identified variants, the examined study samples do not have sufficient power to detect potential interactions.

In conclusion, we have examined the minimal promoter of the GLUT2 gene for nucleotide variability in Danish Caucasian type 2 diabetic patients and have identified 4-bp substitutions. None of the variants were positioned in known binding sites for transcription factors. The variants were not associated to diabetes or with intermediary prediabetic phenotypes in healthy Danish Caucasians.

	Acknowledgments

 
We thank Annemette Forman, Lene Aabo, Bente Mottlau, Susanne Kjellberg, Jane Brønnum, and Quan Truong for dedicated and careful technical assistance and Grete Lademann for secretarial support.

Received October 31, 2000.

Revised February 5, 2001.

Accepted February 5, 2001.

	References

Top Abstract Introduction Materials and Methods Results Discussion References

 

1. Doria A, Plengvidhya N. 2000 Recent advances in the genetics of maturity-onset diabetes of the young and other forms of autosomal dominant diabetes. Curr Opin Endocrinol Diabetes. 7:203–210.[CrossRef]
2. Newgard CB, Quaade C, Hughes SD, Milburn JL. 1990 Glucokinase and glucose transporter expression in liver and islets: implications for control of glucose homoeostasis. Biochem Soc Trans. 18:851–853.[Medline]
3. Matschinsky FM. 1990 Glucokinase as glucose sensor and metabolic signal generator in pancreatic ß-cells and hepatocytes. Diabetes. 39:647–652.[Abstract]
4. Shepherd PR, Kahn BB. 1999 Glucose transporters and insulin action: implications for insulin resistance and diabetes mellitus. N Engl J Med. 341:248–257.[Free Full Text]
5. Guillam MT, Hummler E, Schaerer E, et al. 1997 Early diabetes and abnormal postnatal pancreatic islet development in mice lacking Glut-2. Nat Genet. 17:327–330.[Medline]
6. Valera A, Solanes G, Fernandez-Alvarez J, et al. 1994 Expression of GLUT-2 antisense RNA in ß-cells of transgenic mice leads to diabetes. J Biol Chem. 269:28543–28546.[Abstract/Free Full Text]
7. Santer R, Schneppenheim R, Dombrowski A, Gotze H, Steinmann B, Schaub J. 1997 Mutations in GLUT2, the gene for the liver-type glucose transporter, in patients with Fanconi-Bickel syndrome. Nat Genet. 17:324–326.[CrossRef][Medline]
8. Janssen RC, Bogardus C, Takeda J, Knowler WC, Thompson DB. 1994 Linkage analysis of acute insulin secretion with GLUT2 and glucokinase in Pima Indians and the identification of a missense mutation in GLUT2. Diabetes. 43:558–563.[Abstract]
9. Matsubara A, Tanizawa Y, Matsutani A, Kaneko T, Kaku K. 1995 Sequence variations of the pancreatic islet/liver glucose transporter (GLUT2) gene in Japanese subjects with noninsulin-dependent diabetes mellitus. J Clin Endocrinol Metab. 80:3131–3135.[Abstract]
10. Tanizawa Y, Riggs AC, Chiu KC, et al. 1994 Variability of the pancreatic islet ß cell/liver (GLUT 2) glucose transporter gene in NIDDM patients. Diabetologia. 37:420–427.[Medline]
11. Mueckler M, Kruse M, Strube M, Riggs AC, Chiu KC, Permutt MA. 1994 A mutation in the Glut2 glucose transporter gene of a diabetic patient abolishes transport activity. J Biol Chem. 269:17765–17767.[Abstract/Free Full Text]
12. Hansen T, Andersen CB, Echwald SM, et al. 1997 Identification of a common amino acid polymorphism in the p85 regulatory subunit of phosphatidylinositol 3-kinase: effects on glucose disappearance constant, glucose effectiveness, and the insulin sensitivity index. Diabetes. 46:494–501.[Abstract]
13. Jonsson J, Carlsson L, Edlund T, Edlund H. 1994 Insulin-promoter-factor 1 is required for pancreas development in mice. Nature. 371:606–609.[CrossRef][Medline]
14. Chen WS, Manova K, Weinstein DC, et al. 1994 Disruption of the HNF-4 gene, expressed in visceral endoderm, leads to cell death in embryonic ectoderm and impaired gastrulation of mouse embryos. Genes Dev. 8:2466–2477.[Abstract/Free Full Text]
15. Ahlgren U, Jonsson J, Jonsson L, Simu K, Edlund H. 1998 ß-cell-specific inactivation of the mouse Ipf1/Pdx1 gene results in loss of the ß-cell phenotype and maturity onset diabetes. Genes Dev. 12:1763–1768.[Abstract/Free Full Text]
16. Stoffel M, Duncan SA. 1997 The maturity-onset diabetes of the young (MODY1) transcription factor HNF4 regulates expression of genes required for glucose transport and metabolism. Proc Natl Acad Sci USA. 94:13209–13214.[Abstract/Free Full Text]
17. Yamagata K, Moriwaki M, Nammo T, et al. 2000 Dominant negative HNF-1 mutant affects the normal development of pancreatic ß cells. Diabetes. 49[Suppl 1]:A198.
18. Ban N, Yamada Y, Someya Y, Ihara Y, Tsuda K, Seino Y. 2000 HNF-1 recruits the transcriptional coactivator p300 on the human GLUT2 gene promoter. Diabetes. 49[Suppl 1]:A175.
19. Waeber G, Thompson N, Nicod P, Bonny C. 1996 Transcriptional activation of the GLUT2 gene by the IPF-1/STF-1/IDX-1 homeobox factor. Mol Endocrinol. 10:1327–1334.[Abstract/Free Full Text]

This article has been cited by other articles:

				K. M. Eny, T. M. S. Wolever, B. Fontaine-Bisson, and A. El-Sohemy Genetic variant in the glucose transporter type 2 is associated with higher intakes of sugars in two distinct populations Physiol Genomics, May 1, 2008; 33(3): 355 - 360. [Abstract] [Full Text] [PDF]

				T. O. Kilpelainen, T. A. Lakka, D. E. Laaksonen, O. Laukkanen, J. Lindstrom, J. G. Eriksson, T. T. Valle, H. Hamalainen, S. Aunola, P. Ilanne-Parikka, et al. Physical activity modifies the effect of SNPs in the SLC2A2 (GLUT2) and ABCC8 (SUR1) genes on the risk of developing type 2 diabetes Physiol Genomics, October 19, 2007; 31(2): 264 - 272. [Abstract] [Full Text] [PDF]

				O. Laukkanen, J. Lindstrom, J. Eriksson, T. T. Valle, H. Hamalainen, P. Ilanne-Parikka, S. Keinanen-Kiukaanniemi, J. Tuomilehto, M. Uusitupa, and M. Laakso Polymorphisms in the SLC2A2 (GLUT2) Gene Are Associated With the Conversion From Impaired Glucose Tolerance to Type 2 Diabetes: The Finnish Diabetes Prevention Study Diabetes, July 1, 2005; 54(7): 2256 - 2260. [Abstract] [Full Text] [PDF]

				T. M. Frayling, C. M. Lindgren, J. C. Chevre, S. Menzel, M. Wishart, Y. Benmezroua, A. Brown, J. C. Evans, P. S. Rao, C. Dina, et al. A Genome-Wide Scan in Families With Maturity-Onset Diabetes of the Young: Evidence for Further Genetic Heterogeneity Diabetes, March 1, 2003; 52(3): 872 - 881. [Abstract] [Full Text] [PDF]

				J.-y. Cha, H.-s. Kim, H.-i. Kim, S.-s. Im, S.-y. Kim, J.-w. Kim, B.-i. Yeh, and Y.-h. Ahn Analysis of Polymorphism of the GLUT2 Promoter in NIDDM Patients and its Functional Consequence to the Promoter Activity Ann. Clin. Lab. Sci., April 1, 2002; 32(2): 114 - 122. [Abstract] [Full Text] [PDF]

This Article Abstract Full Text (PDF) Submit a related Letter to the Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Møller, A. M. Articles by Pedersen, O. Search for Related Content PubMed PubMed Citation Articles by Møller, A. M. Articles by Pedersen, O.