Common variations in the genes encoding C-reactive protein, tumor necrosis factor-α, and interleukin-6, and the risk of clinical diabetes in the women's health initiative observational study

Kei Hang K. Chan, Kathleen Brennan, Nai Chieh Y. You, Xuyang Lu, Yiqing Song, Yi Hsiang Hsu, Gautum Chaudhuri, Lauren Nathan, Lesley Tinker, Simin Liu

Research output: Contribution to journalArticle

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Abstract

BACKGROUND: Circulating concentrations of high-sensitivity C-reactive protein (CRP), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) have been associated with an increased risk of diabetes. METHODS: To examine the roles of genetic variation in the genes encoding CRP, TNF- α, and IL-6 in the development of diabetes, we conducted a prospective case-control study nested within the Women's Health Initiative Observational Study. We followed 82 069 postmenopausal women (50-79 years of age) with no history of diabetes for incident diabetes for a mean follow-up of 5.5 years. We identified 1584 cases and matched them with 2198 controls with respect to age, ethnicity, clinical center, time of blood draw, and length of follow-up. We genotyped 13 haplotype-tagging single-nucleotide polymorphisms (tSNPs) across 2.3 kb of the CRP (C-reactive protein, pentraxin-related) gene, 16 tSNPs across 2.8 kb of the TNF (tumor necrosis factor) gene, and 14 tSNPs across 4.8 kb of the IL6 [interleukin 6 (interferon, beta 2)] gene. Plasma concentrations of TNF-α receptor 2 (TNF-α-R2) and IL-6 were measured. RESULTS: After adjusting for matching factors, confounding variables, and multiple comparisons, we found 8 variants in the TNF gene to be associated with plasma TNF-α-R2 concentrations in white women (q < 0.05). After adjusting for multiple comparisons (q > 0.05), we found no association of any IL6 gene variant with plasma IL-6 concentration, nor did we find any significant associations between any SNPs among these 3 genes and diabetes risk (q > 0.05). CONCLUSIONS: We found modest associations between TNF variants and circulating concentrations of TNF-α-R2. Common variants of the CRP, TNF, and IL6 genes were not significantly associated with risk of clinical diabetes in postmenopausal women.

Original languageEnglish (US)
Pages (from-to)317-325
Number of pages9
JournalClinical Chemistry
Volume57
Issue number2
DOIs
StatePublished - Feb 1 2011
Externally publishedYes

Fingerprint

Gene encoding
Women's Health
Medical problems
C-Reactive Protein
Observational Studies
Interleukin-6
Tumor Necrosis Factor-alpha
Genes
Single Nucleotide Polymorphism
Polymorphism
Nucleotides
Plasmas
Receptors, Tumor Necrosis Factor, Type II
Confounding Factors (Epidemiology)
Haplotypes
Case-Control Studies
Blood

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Biochemistry, medical

Cite this

Common variations in the genes encoding C-reactive protein, tumor necrosis factor-α, and interleukin-6, and the risk of clinical diabetes in the women's health initiative observational study. / Chan, Kei Hang K.; Brennan, Kathleen; You, Nai Chieh Y.; Lu, Xuyang; Song, Yiqing; Hsu, Yi Hsiang; Chaudhuri, Gautum; Nathan, Lauren; Tinker, Lesley; Liu, Simin.

In: Clinical Chemistry, Vol. 57, No. 2, 01.02.2011, p. 317-325.

Research output: Contribution to journalArticle

Chan, Kei Hang K. ; Brennan, Kathleen ; You, Nai Chieh Y. ; Lu, Xuyang ; Song, Yiqing ; Hsu, Yi Hsiang ; Chaudhuri, Gautum ; Nathan, Lauren ; Tinker, Lesley ; Liu, Simin. / Common variations in the genes encoding C-reactive protein, tumor necrosis factor-α, and interleukin-6, and the risk of clinical diabetes in the women's health initiative observational study. In: Clinical Chemistry. 2011 ; Vol. 57, No. 2. pp. 317-325.
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abstract = "BACKGROUND: Circulating concentrations of high-sensitivity C-reactive protein (CRP), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) have been associated with an increased risk of diabetes. METHODS: To examine the roles of genetic variation in the genes encoding CRP, TNF- α, and IL-6 in the development of diabetes, we conducted a prospective case-control study nested within the Women's Health Initiative Observational Study. We followed 82 069 postmenopausal women (50-79 years of age) with no history of diabetes for incident diabetes for a mean follow-up of 5.5 years. We identified 1584 cases and matched them with 2198 controls with respect to age, ethnicity, clinical center, time of blood draw, and length of follow-up. We genotyped 13 haplotype-tagging single-nucleotide polymorphisms (tSNPs) across 2.3 kb of the CRP (C-reactive protein, pentraxin-related) gene, 16 tSNPs across 2.8 kb of the TNF (tumor necrosis factor) gene, and 14 tSNPs across 4.8 kb of the IL6 [interleukin 6 (interferon, beta 2)] gene. Plasma concentrations of TNF-α receptor 2 (TNF-α-R2) and IL-6 were measured. RESULTS: After adjusting for matching factors, confounding variables, and multiple comparisons, we found 8 variants in the TNF gene to be associated with plasma TNF-α-R2 concentrations in white women (q < 0.05). After adjusting for multiple comparisons (q > 0.05), we found no association of any IL6 gene variant with plasma IL-6 concentration, nor did we find any significant associations between any SNPs among these 3 genes and diabetes risk (q > 0.05). CONCLUSIONS: We found modest associations between TNF variants and circulating concentrations of TNF-α-R2. Common variants of the CRP, TNF, and IL6 genes were not significantly associated with risk of clinical diabetes in postmenopausal women.",
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T1 - Common variations in the genes encoding C-reactive protein, tumor necrosis factor-α, and interleukin-6, and the risk of clinical diabetes in the women's health initiative observational study

AU - Chan, Kei Hang K.

AU - Brennan, Kathleen

AU - You, Nai Chieh Y.

AU - Lu, Xuyang

AU - Song, Yiqing

AU - Hsu, Yi Hsiang

AU - Chaudhuri, Gautum

AU - Nathan, Lauren

AU - Tinker, Lesley

AU - Liu, Simin

PY - 2011/2/1

Y1 - 2011/2/1

N2 - BACKGROUND: Circulating concentrations of high-sensitivity C-reactive protein (CRP), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) have been associated with an increased risk of diabetes. METHODS: To examine the roles of genetic variation in the genes encoding CRP, TNF- α, and IL-6 in the development of diabetes, we conducted a prospective case-control study nested within the Women's Health Initiative Observational Study. We followed 82 069 postmenopausal women (50-79 years of age) with no history of diabetes for incident diabetes for a mean follow-up of 5.5 years. We identified 1584 cases and matched them with 2198 controls with respect to age, ethnicity, clinical center, time of blood draw, and length of follow-up. We genotyped 13 haplotype-tagging single-nucleotide polymorphisms (tSNPs) across 2.3 kb of the CRP (C-reactive protein, pentraxin-related) gene, 16 tSNPs across 2.8 kb of the TNF (tumor necrosis factor) gene, and 14 tSNPs across 4.8 kb of the IL6 [interleukin 6 (interferon, beta 2)] gene. Plasma concentrations of TNF-α receptor 2 (TNF-α-R2) and IL-6 were measured. RESULTS: After adjusting for matching factors, confounding variables, and multiple comparisons, we found 8 variants in the TNF gene to be associated with plasma TNF-α-R2 concentrations in white women (q < 0.05). After adjusting for multiple comparisons (q > 0.05), we found no association of any IL6 gene variant with plasma IL-6 concentration, nor did we find any significant associations between any SNPs among these 3 genes and diabetes risk (q > 0.05). CONCLUSIONS: We found modest associations between TNF variants and circulating concentrations of TNF-α-R2. Common variants of the CRP, TNF, and IL6 genes were not significantly associated with risk of clinical diabetes in postmenopausal women.

AB - BACKGROUND: Circulating concentrations of high-sensitivity C-reactive protein (CRP), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) have been associated with an increased risk of diabetes. METHODS: To examine the roles of genetic variation in the genes encoding CRP, TNF- α, and IL-6 in the development of diabetes, we conducted a prospective case-control study nested within the Women's Health Initiative Observational Study. We followed 82 069 postmenopausal women (50-79 years of age) with no history of diabetes for incident diabetes for a mean follow-up of 5.5 years. We identified 1584 cases and matched them with 2198 controls with respect to age, ethnicity, clinical center, time of blood draw, and length of follow-up. We genotyped 13 haplotype-tagging single-nucleotide polymorphisms (tSNPs) across 2.3 kb of the CRP (C-reactive protein, pentraxin-related) gene, 16 tSNPs across 2.8 kb of the TNF (tumor necrosis factor) gene, and 14 tSNPs across 4.8 kb of the IL6 [interleukin 6 (interferon, beta 2)] gene. Plasma concentrations of TNF-α receptor 2 (TNF-α-R2) and IL-6 were measured. RESULTS: After adjusting for matching factors, confounding variables, and multiple comparisons, we found 8 variants in the TNF gene to be associated with plasma TNF-α-R2 concentrations in white women (q < 0.05). After adjusting for multiple comparisons (q > 0.05), we found no association of any IL6 gene variant with plasma IL-6 concentration, nor did we find any significant associations between any SNPs among these 3 genes and diabetes risk (q > 0.05). CONCLUSIONS: We found modest associations between TNF variants and circulating concentrations of TNF-α-R2. Common variants of the CRP, TNF, and IL6 genes were not significantly associated with risk of clinical diabetes in postmenopausal women.

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