Variations in the G6PC2/ABCB11 genomic region are associated with fasting glucose levels
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Variations in the G6PC2/ABCB11 genomic region are associated with fasting glucose levels. / Chen, Wei-Min; Erdos, Michael R; Jackson, Anne U; Saxena, Richa; Sanna, Serena; Silver, Kristi D; Timpson, Nicholas J; Hansen, Torben; Orrù, Marco; Grazia Piras, Maria; Bonnycastle, Lori L; Willer, Cristen J; Lyssenko, Valeriya; Shen, Haiqing; Kuusisto, Johanna; Ebrahim, Shah; Sestu, Natascia; Duren, William L; Spada, Maria Cristina; Stringham, Heather M; Scott, Laura J; Olla, Nazario; Swift, Amy J; Najjar, Samer; Mitchell, Braxton D; Lawlor, Debbie A; Smith, George Davey; Ben-Shlomo, Yoav; Andersen, Gitte; Borch-Johnsen, Knut; Jørgensen, Torben; Saramies, Jouko; Valle, Timo T; Buchanan, Thomas A; Shuldiner, Alan R; Lakatta, Edward; Bergman, Richard N; Uda, Manuela; Tuomilehto, Jaakko; Pedersen, Oluf; Cao, Antonio; Groop, Leif; Mohlke, Karen L; Laakso, Markku; Schlessinger, David; Collins, Francis S; Altshuler, David; Abecasis, Gonçalo R; Boehnke, Michael; Scuteri, Angelo; Watanabe, Richard M.
I: Journal of Clinical Investigation, Bind 118, Nr. 7, 2008, s. 2620-8.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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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
VL - 118
SP - 2620
EP - 2628
JO - Journal of Clinical Investigation
JF - Journal of Clinical Investigation
SN - 0021-9738
IS - 7
ER -
ID: 13206124