Association of a functional 17beta-estradiol sensitive IL6-174G/C promoter polymorphism with early-onset type 1 diabetes in females

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Standard

Association of a functional 17beta-estradiol sensitive IL6-174G/C promoter polymorphism with early-onset type 1 diabetes in females. / Kristiansen, Ole P; Nolsøe, Runa L; Larsen, Lykke; Gjesing, Anette M P; Johannesen, Jesper; Larsen, Zenia Mee Effenberger; Lykkesfeldt, Anne E; Karlsen, Allan E; Pociot, Flemming; Mandrup-Poulsen, Thomas; DIEGG.

In: Human Molecular Genetics, Vol. 12, No. 10, 15.05.2003, p. 1101-10.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Kristiansen, OP, Nolsøe, RL, Larsen, L, Gjesing, AMP, Johannesen, J, Larsen, ZME, Lykkesfeldt, AE, Karlsen, AE, Pociot, F, Mandrup-Poulsen, T & DIEGG 2003, 'Association of a functional 17beta-estradiol sensitive IL6-174G/C promoter polymorphism with early-onset type 1 diabetes in females', Human Molecular Genetics, vol. 12, no. 10, pp. 1101-10.

APA

Kristiansen, O. P., Nolsøe, R. L., Larsen, L., Gjesing, A. M. P., Johannesen, J., Larsen, Z. M. E., Lykkesfeldt, A. E., Karlsen, A. E., Pociot, F., Mandrup-Poulsen, T., & DIEGG (2003). Association of a functional 17beta-estradiol sensitive IL6-174G/C promoter polymorphism with early-onset type 1 diabetes in females. Human Molecular Genetics, 12(10), 1101-10.

Vancouver

Kristiansen OP, Nolsøe RL, Larsen L, Gjesing AMP, Johannesen J, Larsen ZME et al. Association of a functional 17beta-estradiol sensitive IL6-174G/C promoter polymorphism with early-onset type 1 diabetes in females. Human Molecular Genetics. 2003 May 15;12(10):1101-10.

Author

Kristiansen, Ole P ; Nolsøe, Runa L ; Larsen, Lykke ; Gjesing, Anette M P ; Johannesen, Jesper ; Larsen, Zenia Mee Effenberger ; Lykkesfeldt, Anne E ; Karlsen, Allan E ; Pociot, Flemming ; Mandrup-Poulsen, Thomas ; DIEGG. / Association of a functional 17beta-estradiol sensitive IL6-174G/C promoter polymorphism with early-onset type 1 diabetes in females. In: Human Molecular Genetics. 2003 ; Vol. 12, No. 10. pp. 1101-10.

Bibtex

@article{4f7f008922f0460b9eb9b58da2f79326,
title = "Association of a functional 17beta-estradiol sensitive IL6-174G/C promoter polymorphism with early-onset type 1 diabetes in females",
abstract = "The type 1 diabetes mellitus (T1DM) candidate gene SNP IL6-174G/C was genotyped in 253 Danish T1DM families (1129 individuals). TDT analysis demonstrated linkage in the presence of association between the IL6-174C allele and T1DM in the 416 T1DM offspring, P(tdt)=0.04. Gender conditioned TDT analyses revealed that linkage and association with T1DM were present in females exclusively; P(tdt)=6.5 x 10(-4) and P(tdt)=2.4 x 10(-4), respectively. Random transmission of the IL6-174C/G alleles was found in T1DM males, non-T1DM males and non-T1DM females; all P(tdt)>/=0.37. Heterogeneity analyses (T1DM versus non-T1DM females) excluded preferential meiotic segregation in females, P=4.6 x 10(-3), and demonstrated differences in the transmission patterns between female and male T1DM offspring, P=5.1 x 10(-3). The IL6-174 CC genotype was associated with younger age at onset of T1DM in females (P=0.002). The impact of 17beta-estradiol (E(2)) on the IL6-174G/C variants was investigated by reporter studies. The PMA stimulated activity of the T1DM risk IL6-174C variant exceeded that of the T1DM protective IL6-174G variant by approximately 70% in the absence of E(2) (P(c)=0.004), but not with E(2) present (P(c)=0.12). The PMA stimulated activity of the IL6-174G variant was repressed without E(2) present, but was derepressed by addition of E(2), P(c)=0.024. In contrast, the PMA stimulated IL6-174C activity was unaffected by E(2) as were the constitutive activities of the IL6-174G/C variants. In conclusion, higher IL6 promoter activity may confer risk to T1DM in very young females. This excess risk is negated with increasing age, possibly by the increasing E(2) levels in puberty.",
keywords = "Age of Onset, Animals, Diabetes Mellitus, Type 1, Estradiol, Female, Humans, Interleukin-6, Male, Mice, Polymorphism, Genetic, Promoter Regions, Genetic, Sex Factors",
author = "Kristiansen, {Ole P} and Nols{\o}e, {Runa L} and Lykke Larsen and Gjesing, {Anette M P} and Jesper Johannesen and Larsen, {Zenia Mee Effenberger} and Lykkesfeldt, {Anne E} and Karlsen, {Allan E} and Flemming Pociot and Thomas Mandrup-Poulsen and DIEGG",
year = "2003",
month = may,
day = "15",
language = "English",
volume = "12",
pages = "1101--10",
journal = "Human Molecular Genetics",
issn = "0964-6906",
publisher = "Oxford University Press",
number = "10",

}

RIS

TY - JOUR

T1 - Association of a functional 17beta-estradiol sensitive IL6-174G/C promoter polymorphism with early-onset type 1 diabetes in females

AU - Kristiansen, Ole P

AU - Nolsøe, Runa L

AU - Larsen, Lykke

AU - Gjesing, Anette M P

AU - Johannesen, Jesper

AU - Larsen, Zenia Mee Effenberger

AU - Lykkesfeldt, Anne E

AU - Karlsen, Allan E

AU - Pociot, Flemming

AU - Mandrup-Poulsen, Thomas

AU - DIEGG

PY - 2003/5/15

Y1 - 2003/5/15

N2 - The type 1 diabetes mellitus (T1DM) candidate gene SNP IL6-174G/C was genotyped in 253 Danish T1DM families (1129 individuals). TDT analysis demonstrated linkage in the presence of association between the IL6-174C allele and T1DM in the 416 T1DM offspring, P(tdt)=0.04. Gender conditioned TDT analyses revealed that linkage and association with T1DM were present in females exclusively; P(tdt)=6.5 x 10(-4) and P(tdt)=2.4 x 10(-4), respectively. Random transmission of the IL6-174C/G alleles was found in T1DM males, non-T1DM males and non-T1DM females; all P(tdt)>/=0.37. Heterogeneity analyses (T1DM versus non-T1DM females) excluded preferential meiotic segregation in females, P=4.6 x 10(-3), and demonstrated differences in the transmission patterns between female and male T1DM offspring, P=5.1 x 10(-3). The IL6-174 CC genotype was associated with younger age at onset of T1DM in females (P=0.002). The impact of 17beta-estradiol (E(2)) on the IL6-174G/C variants was investigated by reporter studies. The PMA stimulated activity of the T1DM risk IL6-174C variant exceeded that of the T1DM protective IL6-174G variant by approximately 70% in the absence of E(2) (P(c)=0.004), but not with E(2) present (P(c)=0.12). The PMA stimulated activity of the IL6-174G variant was repressed without E(2) present, but was derepressed by addition of E(2), P(c)=0.024. In contrast, the PMA stimulated IL6-174C activity was unaffected by E(2) as were the constitutive activities of the IL6-174G/C variants. In conclusion, higher IL6 promoter activity may confer risk to T1DM in very young females. This excess risk is negated with increasing age, possibly by the increasing E(2) levels in puberty.

AB - The type 1 diabetes mellitus (T1DM) candidate gene SNP IL6-174G/C was genotyped in 253 Danish T1DM families (1129 individuals). TDT analysis demonstrated linkage in the presence of association between the IL6-174C allele and T1DM in the 416 T1DM offspring, P(tdt)=0.04. Gender conditioned TDT analyses revealed that linkage and association with T1DM were present in females exclusively; P(tdt)=6.5 x 10(-4) and P(tdt)=2.4 x 10(-4), respectively. Random transmission of the IL6-174C/G alleles was found in T1DM males, non-T1DM males and non-T1DM females; all P(tdt)>/=0.37. Heterogeneity analyses (T1DM versus non-T1DM females) excluded preferential meiotic segregation in females, P=4.6 x 10(-3), and demonstrated differences in the transmission patterns between female and male T1DM offspring, P=5.1 x 10(-3). The IL6-174 CC genotype was associated with younger age at onset of T1DM in females (P=0.002). The impact of 17beta-estradiol (E(2)) on the IL6-174G/C variants was investigated by reporter studies. The PMA stimulated activity of the T1DM risk IL6-174C variant exceeded that of the T1DM protective IL6-174G variant by approximately 70% in the absence of E(2) (P(c)=0.004), but not with E(2) present (P(c)=0.12). The PMA stimulated activity of the IL6-174G variant was repressed without E(2) present, but was derepressed by addition of E(2), P(c)=0.024. In contrast, the PMA stimulated IL6-174C activity was unaffected by E(2) as were the constitutive activities of the IL6-174G/C variants. In conclusion, higher IL6 promoter activity may confer risk to T1DM in very young females. This excess risk is negated with increasing age, possibly by the increasing E(2) levels in puberty.

KW - Age of Onset

KW - Animals

KW - Diabetes Mellitus, Type 1

KW - Estradiol

KW - Female

KW - Humans

KW - Interleukin-6

KW - Male

KW - Mice

KW - Polymorphism, Genetic

KW - Promoter Regions, Genetic

KW - Sex Factors

M3 - Journal article

C2 - 12719374

VL - 12

SP - 1101

EP - 1110

JO - Human Molecular Genetics

JF - Human Molecular Genetics

SN - 0964-6906

IS - 10

ER -

ID: 45583507