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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 and Grazia Piras, Maria, et al. (2008) In Journal of Clinical Investigation Jun 2. p.2620-2628
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... (More)
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. (Less)
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Journal of Clinical Investigation
volume
Jun 2
pages
2620 - 2628
publisher
American Society for Clinical Investigation
external identifiers
  • wos:000257657400029
  • pmid:18521185
  • scopus:46749100599
ISSN
0021-9738
DOI
10.1172/JCI34566
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English
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yes
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dfa3d4ed-b291-4310-9120-30ed245f1905 (old id 1169242)
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http://www.ncbi.nlm.nih.gov/pubmed/18521185?dopt=Abstract
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2008-07-03 09:22:17
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@article{dfa3d4ed-b291-4310-9120-30ed245f1905,
  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       = {Chen, Wei-Min and Erdos, Michael R and Jackson, Anne U and Saxena, Richa and Sanna, Serena and Silver, Kristi D and Timpson, Nicholas J and Hansen, Torben and Orrù, Marco and Grazia Piras, Maria and Bonnycastle, Lori L and Willer, Cristen J and Lyssenko, Valeriya and Shen, Haiqing and Kuusisto, Johanna and Ebrahim, Shah and Sestu, Natascia and Duren, William L and Spada, Maria Cristina and Stringham, Heather M and Scott, Laura J and Olla, Nazario and Swift, Amy J and Najjar, Samer and Mitchell, Braxton D and Lawlor, Debbie A and Smith, George Davey and Ben-Shlomo, Yoav and Andersen, Gitte and Borch-Johnsen, Knut and Jørgensen, Torben and Saramies, Jouko and Valle, Timo T and Buchanan, Thomas A and Shuldiner, Alan R and Lakatta, Edward and Bergman, Richard N and Uda, Manuela and Tuomilehto, Jaakko and Pedersen, Oluf and Cao, Antonio and Groop, Leif and Mohlke, Karen L and Laakso, Markku and Schlessinger, David and Collins, Francis S and Altshuler, David and Abecasis, Gonçalo R and Boehnke, Michael and Scuteri, Angelo and Watanabe, Richard M},
  issn         = {0021-9738},
  language     = {eng},
  pages        = {2620--2628},
  publisher    = {American Society for Clinical Investigation},
  series       = {Journal of Clinical Investigation},
  title        = {Variations in the G6PC2/ABCB11 genomic region are associated with fasting glucose levels.},
  url          = {http://dx.doi.org/10.1172/JCI34566},
  volume       = {Jun 2},
  year         = {2008},
}