Variations in the G6PC2/ABCB11 genomic region are associated with fasting glucose levels

Wei-Min Chen; Michael R Erdos; Anne U Jackson; Richa Saxena; Serena Sanna; Kristi D Silver; Nicholas J Timpson; Torben Hansen; Marco Orrù; Maria Grazia Piras; Lori L Bonnycastle; Cristen J Willer; Valeriya Lyssenko; Haiqing Shen; Johanna Kuusisto; Shah Ebrahim; Natascia Sestu; William L Duren; Maria Cristina Spada; Heather M Stringham; Laura J Scott; Nazario Olla; Amy J Swift; Samer Najjar; Braxton D Mitchell; Debbie A Lawlor; George Davey Smith; Yoav Ben-Shlomo; Gitte Andersen; Knut Borch-Johnsen; Torben Jørgensen; Jouko Saramies; Timo T Valle; Thomas A Buchanan; Alan R Shuldiner; Edward Lakatta; Richard N Bergman; Manuela Uda; Jaakko Tuomilehto; Oluf Pedersen; Antonio Cao; Leif Groop; Karen L Mohlke; Markku Laakso; David Schlessinger; Francis S Collins; David Altshuler; Gonçalo R Abecasis; Michael Boehnke; Angelo Scuteri; Richard M Watanabe

doi:10.1172/JCI34566

Variations in the G6PC2/ABCB11 genomic region are associated with fasting glucose levels

Wei-Min Chen, Michael R Erdos, Anne U Jackson, Richa Saxena, Serena Sanna, Kristi D Silver, Nicholas J Timpson, Torben Hansen, Marco Orrù, Maria Grazia Piras, Lori L Bonnycastle, Cristen J Willer, Valeriya Lyssenko, Haiqing Shen, Johanna Kuusisto, Shah Ebrahim, Natascia Sestu, William L Duren, Maria Cristina Spada, Heather M StringhamLaura J Scott, Nazario Olla, Amy J Swift, Samer Najjar, Braxton D Mitchell, Debbie A Lawlor, George Davey Smith, Yoav Ben-Shlomo, Gitte Andersen, Knut Borch-Johnsen, Torben Jørgensen, Jouko Saramies, Timo T Valle, Thomas A Buchanan, Alan R Shuldiner, Edward Lakatta, Richard N Bergman, Manuela Uda, Jaakko Tuomilehto, Oluf Pedersen, Antonio Cao, Leif Groop, Karen L Mohlke, Markku Laakso, David Schlessinger, Francis S Collins, David Altshuler, Gonçalo R Abecasis, Michael Boehnke, Angelo Scuteri, Richard M Watanabe

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › peer review

145 Citationer (Scopus)

Abstract

Udgivelsesdato: 2008-Jul

Originalsprog	Engelsk
Tidsskrift	Journal of Clinical Investigation
Vol/bind	118
Udgave nummer	7
Sider (fra-til)	2620-8
Antal sider	8
ISSN	0021-9738
DOI	https://doi.org/10.1172/JCI34566
Status	Udgivet - 2008

Bibliografisk note

Keywords: ATP-Binding Cassette Transporters; Adult; Aged; Analysis of Variance; Blood Glucose; European Continental Ancestry Group; Fasting; Finland; Follow-Up Studies; Gene Frequency; Genotype; Glucose-6-Phosphatase; Humans; Italy; Linkage Disequilibrium; Middle Aged; Polymorphism, Single Nucleotide

Adgang til dokumentet

10.1172/JCI34566

Citationsformater

Chen, W.-M., Erdos, M. R., Jackson, A. U., Saxena, R., Sanna, S., Silver, K. D., Timpson, N. J., Hansen, T., Orrù, M., Grazia Piras, M., Bonnycastle, L. L., Willer, C. J., Lyssenko, V., Shen, H., Kuusisto, J., Ebrahim, S., Sestu, N., Duren, W. L., Spada, M. C., ... Watanabe, R. M. (2008). Variations in the G6PC2/ABCB11 genomic region are associated with fasting glucose levels. Journal of Clinical Investigation, 118(7), 2620-8. https://doi.org/10.1172/JCI34566

Chen, W-M, Erdos, MR, Jackson, AU, Saxena, R, Sanna, S, Silver, KD, Timpson, NJ, Hansen, T, Orrù, M, Grazia Piras, M, Bonnycastle, LL, Willer, CJ, Lyssenko, V, Shen, H, Kuusisto, J, Ebrahim, S, Sestu, N, Duren, WL, Spada, MC, Stringham, HM, Scott, LJ, Olla, N, Swift, AJ, Najjar, S, Mitchell, BD, Lawlor, DA, Smith, GD, Ben-Shlomo, Y, Andersen, G, Borch-Johnsen, K, Jørgensen, T, Saramies, J, Valle, TT, Buchanan, TA, Shuldiner, AR, Lakatta, E, Bergman, RN, Uda, M, Tuomilehto, J, Pedersen, O, Cao, A, Groop, L, Mohlke, KL, Laakso, M, Schlessinger, D, Collins, FS, Altshuler, D, Abecasis, GR, Boehnke, M, Scuteri, A & Watanabe, RM 2008, 'Variations in the G6PC2/ABCB11 genomic region are associated with fasting glucose levels', Journal of Clinical Investigation, bind 118, nr. 7, s. 2620-8. https://doi.org/10.1172/JCI34566

@article{0adbbd0071f611de8bc9000ea68e967b,

title = "Variations in the G6PC2/ABCB11 genomic region are associated with fasting glucose levels",

abstract = "Identifying the genetic variants that regulate fasting glucose concentrations may further our understanding of the pathogenesis of diabetes. We therefore investigated the association of fasting glucose levels with SNPs in 2 genome-wide scans including a total of 5,088 nondiabetic individuals from Finland and Sardinia. We found a significant association between the SNP rs563694 and fasting glucose concentrations (P = 3.5 x 10(-7)). This association was further investigated in an additional 18,436 nondiabetic individuals of mixed European descent from 7 different studies. The combined P value for association in these follow-up samples was 6.9 x 10(-26), and combining results from all studies resulted in an overall P value for association of 6.4 x 10(-33). Across these studies, fasting glucose concentrations increased 0.01-0.16 mM with each copy of the major allele, accounting for approximately 1% of the total variation in fasting glucose. The rs563694 SNP is located between the genes glucose-6-phosphatase catalytic subunit 2 (G6PC2) and ATP-binding cassette, subfamily B (MDR/TAP), member 11 (ABCB11). Our results in combination with data reported in the literature suggest that G6PC2, a glucose-6-phosphatase almost exclusively expressed in pancreatic islet cells, may underlie variation in fasting glucose, though it is possible that ABCB11, which is expressed primarily in liver, may also contribute to such variation.",

author = "Wei-Min Chen and Erdos, {Michael R} and Jackson, {Anne U} and Richa Saxena and Serena Sanna and Silver, {Kristi D} and Timpson, {Nicholas J} and Torben Hansen and Marco Orr{\`u} and {Grazia Piras}, Maria and Bonnycastle, {Lori L} and Willer, {Cristen J} and Valeriya Lyssenko and Haiqing Shen and Johanna Kuusisto and Shah Ebrahim and Natascia Sestu and Duren, {William L} and Spada, {Maria Cristina} and Stringham, {Heather M} and Scott, {Laura J} and Nazario Olla and Swift, {Amy J} and Samer Najjar and Mitchell, {Braxton D} and Lawlor, {Debbie A} and Smith, {George Davey} and Yoav Ben-Shlomo and Gitte Andersen and Knut Borch-Johnsen and Torben J{\o}rgensen and Jouko Saramies and Valle, {Timo T} and Buchanan, {Thomas A} and Shuldiner, {Alan R} and Edward Lakatta and Bergman, {Richard N} and Manuela Uda and Jaakko Tuomilehto and Oluf Pedersen and Antonio Cao and Leif Groop and Mohlke, {Karen L} and Markku Laakso and David Schlessinger and Collins, {Francis S} and David Altshuler and Abecasis, {Gon{\c c}alo R} and Michael Boehnke and Angelo Scuteri and Watanabe, {Richard M}",

note = "Keywords: ATP-Binding Cassette Transporters; Adult; Aged; Analysis of Variance; Blood Glucose; European Continental Ancestry Group; Fasting; Finland; Follow-Up Studies; Gene Frequency; Genotype; Glucose-6-Phosphatase; Humans; Italy; Linkage Disequilibrium; Middle Aged; Polymorphism, Single Nucleotide",

year = "2008",

doi = "10.1172/JCI34566",

language = "English",

volume = "118",

pages = "2620--8",

journal = "Journal of Clinical Investigation",

issn = "0021-9738",

publisher = "American Society for Clinical Investigation",

number = "7",

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TY - JOUR

T1 - Variations in the G6PC2/ABCB11 genomic region are associated with fasting glucose levels

AU - Chen, Wei-Min

AU - Erdos, Michael R

AU - Jackson, Anne U

AU - Saxena, Richa

AU - Sanna, Serena

AU - Silver, Kristi D

AU - Timpson, Nicholas J

AU - Hansen, Torben

AU - Orrù, Marco

AU - Grazia Piras, Maria

AU - Bonnycastle, Lori L

AU - Willer, Cristen J

AU - Lyssenko, Valeriya

AU - Shen, Haiqing

AU - Kuusisto, Johanna

AU - Ebrahim, Shah

AU - Sestu, Natascia

AU - Duren, William L

AU - Spada, Maria Cristina

AU - Stringham, Heather M

AU - Scott, Laura J

AU - Olla, Nazario

AU - Swift, Amy J

AU - Najjar, Samer

AU - Mitchell, Braxton D

AU - Lawlor, Debbie A

AU - Smith, George Davey

AU - Ben-Shlomo, Yoav

AU - Andersen, Gitte

AU - Borch-Johnsen, Knut

AU - Jørgensen, Torben

AU - Saramies, Jouko

AU - Valle, Timo T

AU - Buchanan, Thomas A

AU - Shuldiner, Alan R

AU - Lakatta, Edward

AU - Bergman, Richard N

AU - Uda, Manuela

AU - Tuomilehto, Jaakko

AU - Pedersen, Oluf

AU - Cao, Antonio

AU - Groop, Leif

AU - Mohlke, Karen L

AU - Laakso, Markku

AU - Schlessinger, David

AU - Collins, Francis S

AU - Altshuler, David

AU - Abecasis, Gonçalo R

AU - Boehnke, Michael

AU - Scuteri, Angelo

AU - Watanabe, Richard M

N1 - Keywords: ATP-Binding Cassette Transporters; Adult; Aged; Analysis of Variance; Blood Glucose; European Continental Ancestry Group; Fasting; Finland; Follow-Up Studies; Gene Frequency; Genotype; Glucose-6-Phosphatase; Humans; Italy; Linkage Disequilibrium; Middle Aged; Polymorphism, Single Nucleotide

PY - 2008

Y1 - 2008

N2 - Identifying the genetic variants that regulate fasting glucose concentrations may further our understanding of the pathogenesis of diabetes. We therefore investigated the association of fasting glucose levels with SNPs in 2 genome-wide scans including a total of 5,088 nondiabetic individuals from Finland and Sardinia. We found a significant association between the SNP rs563694 and fasting glucose concentrations (P = 3.5 x 10(-7)). This association was further investigated in an additional 18,436 nondiabetic individuals of mixed European descent from 7 different studies. The combined P value for association in these follow-up samples was 6.9 x 10(-26), and combining results from all studies resulted in an overall P value for association of 6.4 x 10(-33). Across these studies, fasting glucose concentrations increased 0.01-0.16 mM with each copy of the major allele, accounting for approximately 1% of the total variation in fasting glucose. The rs563694 SNP is located between the genes glucose-6-phosphatase catalytic subunit 2 (G6PC2) and ATP-binding cassette, subfamily B (MDR/TAP), member 11 (ABCB11). Our results in combination with data reported in the literature suggest that G6PC2, a glucose-6-phosphatase almost exclusively expressed in pancreatic islet cells, may underlie variation in fasting glucose, though it is possible that ABCB11, which is expressed primarily in liver, may also contribute to such variation.

AB - Identifying the genetic variants that regulate fasting glucose concentrations may further our understanding of the pathogenesis of diabetes. We therefore investigated the association of fasting glucose levels with SNPs in 2 genome-wide scans including a total of 5,088 nondiabetic individuals from Finland and Sardinia. We found a significant association between the SNP rs563694 and fasting glucose concentrations (P = 3.5 x 10(-7)). This association was further investigated in an additional 18,436 nondiabetic individuals of mixed European descent from 7 different studies. The combined P value for association in these follow-up samples was 6.9 x 10(-26), and combining results from all studies resulted in an overall P value for association of 6.4 x 10(-33). Across these studies, fasting glucose concentrations increased 0.01-0.16 mM with each copy of the major allele, accounting for approximately 1% of the total variation in fasting glucose. The rs563694 SNP is located between the genes glucose-6-phosphatase catalytic subunit 2 (G6PC2) and ATP-binding cassette, subfamily B (MDR/TAP), member 11 (ABCB11). Our results in combination with data reported in the literature suggest that G6PC2, a glucose-6-phosphatase almost exclusively expressed in pancreatic islet cells, may underlie variation in fasting glucose, though it is possible that ABCB11, which is expressed primarily in liver, may also contribute to such variation.

U2 - 10.1172/JCI34566

DO - 10.1172/JCI34566

M3 - Journal article

C2 - 18521185

SN - 0021-9738

VL - 118

SP - 2620

EP - 2628

JO - Journal of Clinical Investigation

JF - Journal of Clinical Investigation

IS - 7

ER -