Phosphatidylinositol 3-kinase p85α regulatory subunit gene PIK3R1 haplotype is associated with body fat and serum leptin in a female twin population

Y. Jamshidi, H. Snieder, X. Wang, M. J. Pavitt, T. D. Spector, N. D. Carter, Sandra D. O'Dell

Research output: Contribution to journalArticle

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Abstract

Aims/hypothesis: Phosphatidylinositol 3-kinase (PI3K) couples the leptin and insulin signalling pathways via the insulin receptor substrates IRS1 and IRS2. Hence, defective activation of PI3K could be a novel mechanism of peripheral leptin or insulin resistance. We investigated associations of tagging single-nucleotide polymorphisms (tSNPs) in the PI3K p85α regulatory subunit gene PIK3R1 with anthropometry, leptin, body fat and insulin sensitivity in a female twin population of European extraction. Materials and methods: Eight tSNPs were genotyped in 2,778 women (mean age 47.4±12.5 years) from the St Thomas' UK Adult Twin Registry (Twins UK). Results: SNP rs1550805 was associated with serum leptin (p=0.028), BMI (p=0.025), weight (p=0.019), total fat (p=0.004), total fat percentage (p=0.002), waist circumference (p=0.025), central fat (p=0.005) and central fat percentage (p=0.005). SNPs rs7713645 and rs7709243 were associated with BMI (p=0.020 and p=0.029, respectively), rs7709243 with weight, total and central fat (p=0.026, p=0.031 and p=0.023, respectively) and both SNPs with fasting glucose (p=0.003 and p=0.001, respectively) and glucose 2-h post OGTT (p=0.023 and p=0.007, respectively). Subjects with haplotype 222 (frequency 7.2%) showed higher serum leptin concentration (p=0.007) and body fat measures (p≤0.001 for all), and those with haplotype 221 (frequency 38.7%) showed higher fasting and 2-h glucose (p=0.035 and p=0.021, respectively) compared with subjects with the most common haplotype, 111 (frequency 45.5%). Conclusions/interpretation: Association of the PIK3R1 SNP rs1550805 with serum leptin and body fat may reflect a diminished ability of PI3K to signal via IRS1 or IRS2 in response to leptin.

Original languageEnglish (US)
Pages (from-to)2659-2667
Number of pages9
JournalDiabetologia
Volume49
Issue number11
DOIs
StatePublished - Nov 1 2006

Fingerprint

Phosphatidylinositol 3-Kinase
Regulator Genes
Leptin
Haplotypes
Adipose Tissue
Single Nucleotide Polymorphism
Fats
Serum
Population
Glucose
Insulin Resistance
Fasting
Body Weights and Measures
Weights and Measures
Anthropometry
Aptitude
Insulin Receptor
Waist Circumference
Glucose Tolerance Test
Vascular Resistance

Keywords

  • Cytokines
  • Epidemiology
  • Genetics
  • Obesity
  • Weight regulation

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

Cite this

Phosphatidylinositol 3-kinase p85α regulatory subunit gene PIK3R1 haplotype is associated with body fat and serum leptin in a female twin population. / Jamshidi, Y.; Snieder, H.; Wang, X.; Pavitt, M. J.; Spector, T. D.; Carter, N. D.; O'Dell, Sandra D.

In: Diabetologia, Vol. 49, No. 11, 01.11.2006, p. 2659-2667.

Research output: Contribution to journalArticle

Jamshidi, Y. ; Snieder, H. ; Wang, X. ; Pavitt, M. J. ; Spector, T. D. ; Carter, N. D. ; O'Dell, Sandra D. / Phosphatidylinositol 3-kinase p85α regulatory subunit gene PIK3R1 haplotype is associated with body fat and serum leptin in a female twin population. In: Diabetologia. 2006 ; Vol. 49, No. 11. pp. 2659-2667.
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abstract = "Aims/hypothesis: Phosphatidylinositol 3-kinase (PI3K) couples the leptin and insulin signalling pathways via the insulin receptor substrates IRS1 and IRS2. Hence, defective activation of PI3K could be a novel mechanism of peripheral leptin or insulin resistance. We investigated associations of tagging single-nucleotide polymorphisms (tSNPs) in the PI3K p85α regulatory subunit gene PIK3R1 with anthropometry, leptin, body fat and insulin sensitivity in a female twin population of European extraction. Materials and methods: Eight tSNPs were genotyped in 2,778 women (mean age 47.4±12.5 years) from the St Thomas' UK Adult Twin Registry (Twins UK). Results: SNP rs1550805 was associated with serum leptin (p=0.028), BMI (p=0.025), weight (p=0.019), total fat (p=0.004), total fat percentage (p=0.002), waist circumference (p=0.025), central fat (p=0.005) and central fat percentage (p=0.005). SNPs rs7713645 and rs7709243 were associated with BMI (p=0.020 and p=0.029, respectively), rs7709243 with weight, total and central fat (p=0.026, p=0.031 and p=0.023, respectively) and both SNPs with fasting glucose (p=0.003 and p=0.001, respectively) and glucose 2-h post OGTT (p=0.023 and p=0.007, respectively). Subjects with haplotype 222 (frequency 7.2{\%}) showed higher serum leptin concentration (p=0.007) and body fat measures (p≤0.001 for all), and those with haplotype 221 (frequency 38.7{\%}) showed higher fasting and 2-h glucose (p=0.035 and p=0.021, respectively) compared with subjects with the most common haplotype, 111 (frequency 45.5{\%}). Conclusions/interpretation: Association of the PIK3R1 SNP rs1550805 with serum leptin and body fat may reflect a diminished ability of PI3K to signal via IRS1 or IRS2 in response to leptin.",
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T1 - Phosphatidylinositol 3-kinase p85α regulatory subunit gene PIK3R1 haplotype is associated with body fat and serum leptin in a female twin population

AU - Jamshidi, Y.

AU - Snieder, H.

AU - Wang, X.

AU - Pavitt, M. J.

AU - Spector, T. D.

AU - Carter, N. D.

AU - O'Dell, Sandra D.

PY - 2006/11/1

Y1 - 2006/11/1

N2 - Aims/hypothesis: Phosphatidylinositol 3-kinase (PI3K) couples the leptin and insulin signalling pathways via the insulin receptor substrates IRS1 and IRS2. Hence, defective activation of PI3K could be a novel mechanism of peripheral leptin or insulin resistance. We investigated associations of tagging single-nucleotide polymorphisms (tSNPs) in the PI3K p85α regulatory subunit gene PIK3R1 with anthropometry, leptin, body fat and insulin sensitivity in a female twin population of European extraction. Materials and methods: Eight tSNPs were genotyped in 2,778 women (mean age 47.4±12.5 years) from the St Thomas' UK Adult Twin Registry (Twins UK). Results: SNP rs1550805 was associated with serum leptin (p=0.028), BMI (p=0.025), weight (p=0.019), total fat (p=0.004), total fat percentage (p=0.002), waist circumference (p=0.025), central fat (p=0.005) and central fat percentage (p=0.005). SNPs rs7713645 and rs7709243 were associated with BMI (p=0.020 and p=0.029, respectively), rs7709243 with weight, total and central fat (p=0.026, p=0.031 and p=0.023, respectively) and both SNPs with fasting glucose (p=0.003 and p=0.001, respectively) and glucose 2-h post OGTT (p=0.023 and p=0.007, respectively). Subjects with haplotype 222 (frequency 7.2%) showed higher serum leptin concentration (p=0.007) and body fat measures (p≤0.001 for all), and those with haplotype 221 (frequency 38.7%) showed higher fasting and 2-h glucose (p=0.035 and p=0.021, respectively) compared with subjects with the most common haplotype, 111 (frequency 45.5%). Conclusions/interpretation: Association of the PIK3R1 SNP rs1550805 with serum leptin and body fat may reflect a diminished ability of PI3K to signal via IRS1 or IRS2 in response to leptin.

AB - Aims/hypothesis: Phosphatidylinositol 3-kinase (PI3K) couples the leptin and insulin signalling pathways via the insulin receptor substrates IRS1 and IRS2. Hence, defective activation of PI3K could be a novel mechanism of peripheral leptin or insulin resistance. We investigated associations of tagging single-nucleotide polymorphisms (tSNPs) in the PI3K p85α regulatory subunit gene PIK3R1 with anthropometry, leptin, body fat and insulin sensitivity in a female twin population of European extraction. Materials and methods: Eight tSNPs were genotyped in 2,778 women (mean age 47.4±12.5 years) from the St Thomas' UK Adult Twin Registry (Twins UK). Results: SNP rs1550805 was associated with serum leptin (p=0.028), BMI (p=0.025), weight (p=0.019), total fat (p=0.004), total fat percentage (p=0.002), waist circumference (p=0.025), central fat (p=0.005) and central fat percentage (p=0.005). SNPs rs7713645 and rs7709243 were associated with BMI (p=0.020 and p=0.029, respectively), rs7709243 with weight, total and central fat (p=0.026, p=0.031 and p=0.023, respectively) and both SNPs with fasting glucose (p=0.003 and p=0.001, respectively) and glucose 2-h post OGTT (p=0.023 and p=0.007, respectively). Subjects with haplotype 222 (frequency 7.2%) showed higher serum leptin concentration (p=0.007) and body fat measures (p≤0.001 for all), and those with haplotype 221 (frequency 38.7%) showed higher fasting and 2-h glucose (p=0.035 and p=0.021, respectively) compared with subjects with the most common haplotype, 111 (frequency 45.5%). Conclusions/interpretation: Association of the PIK3R1 SNP rs1550805 with serum leptin and body fat may reflect a diminished ability of PI3K to signal via IRS1 or IRS2 in response to leptin.

KW - Cytokines

KW - Epidemiology

KW - Genetics

KW - Obesity

KW - Weight regulation

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