No link between X chromosome inactivation pattern and simple goiter in females

evidence from a twin study

Thomas Heiberg Brix, Pia Skov Hansen, Gun Peggy S Knudsen, Marianne K Kringen, Kirsten Ohm Kyvik, Karen Helene Orstavik, Laszlo Hegedüs

Publikation: Bidrag til tidsskriftTidsskriftartikelForskning

Resumé

Udgivelsesdato: 2009-Feb
OriginalsprogEngelsk
TidsskriftThyroid
Vol/bind19
Udgave nummer2
Sider (fra-til)165-9
Antal sider4
ISSN1050-7256
DOI
StatusUdgivet - 1. feb. 2009

Fingeraftryk

X Chromosome Inactivation
Twin Studies
Euthyroid Goiter
Polymerase Chain Reaction
Androgen Receptors
DNA Methylation

Citer dette

Brix, T. H., Hansen, P. S., Knudsen, G. P. S., Kringen, M. K., Kyvik, K. O., Orstavik, K. H., & Hegedüs, L. (2009). No link between X chromosome inactivation pattern and simple goiter in females: evidence from a twin study. Thyroid, 19(2), 165-9. https://doi.org/10.1089/thy.2008.0380
Brix, Thomas Heiberg ; Hansen, Pia Skov ; Knudsen, Gun Peggy S ; Kringen, Marianne K ; Kyvik, Kirsten Ohm ; Orstavik, Karen Helene ; Hegedüs, Laszlo. / No link between X chromosome inactivation pattern and simple goiter in females : evidence from a twin study. I: Thyroid. 2009 ; Bind 19, Nr. 2. s. 165-9.
@article{1cfe7ce0024611dea37d000ea68e967b,
title = "No link between X chromosome inactivation pattern and simple goiter in females: evidence from a twin study",
abstract = "BACKGROUND: Simple goiter (SG) comprises diffuse (DG) and nodular (NG) benign nonautoimmune nontoxic goiter. In nonendemic goiter areas, the ratio of females to males may exceed 5:1, indicating that gender and/or sex hormones may play a role in the etiology of SG in these areas. Theoretically, as shown for autoimmune thyroid disease, X chromosome inactivation (XCI) and resultant tissue chimerism could offer a novel explanation for the female preponderance of SG. To examine whether skewed XCI is associated with SG, we first compared XCI in 71 twin individuals with SG with that in 142 unrelated healthy control twin individuals, and then performed a within-pair comparison of XCI in 48 twin pairs discordant for SG. METHODS: DNA was extracted from peripheral blood cells. XCI analysis was performed by predigestion of DNA using the methylation-sensitive enzyme Hpall, followed by polymerase chain reaction of the polymorphic CAG repeat of the androgen receptor gene. A polymerase chain reaction product is obtained from the inactive X chromosome only. The XCI pattern was classified as skewed when 80{\%} or more of the cells preferentially inactivated the same X chromosome. Twin zygosity was established by DNA fingerprinting. RESULTS: The frequency of skewed XCI in female twins with SG, DG, and NG was 11{\%} (8/71), 13{\%} (6/46), and 8{\%} (2/25), respectively, which was not significantly different from the prevalences in the corresponding control populations, 14{\%} (20/142, p = 0.56), 14{\%} (13/92, p = 1.00), and 14{\%} (7/50, p = 0.71), respectively. Essentially, similar results were obtained when comparing the prevalence of skewed XCI in twin pairs discordant for SG (48 pairs), DG (30 pairs), and NG (18 pairs). CONCLUSION: In a sample of Danish female twins, we did not find evidence for involvement of skewed XCI in the etiology or the female preponderance of SG.",
author = "Brix, {Thomas Heiberg} and Hansen, {Pia Skov} and Knudsen, {Gun Peggy S} and Kringen, {Marianne K} and Kyvik, {Kirsten Ohm} and Orstavik, {Karen Helene} and Laszlo Heged{\"u}s",
year = "2009",
month = "2",
day = "1",
doi = "10.1089/thy.2008.0380",
language = "English",
volume = "19",
pages = "165--9",
journal = "Thyroid",
issn = "1050-7256",
publisher = "Mary Ann Liebert Incorporated",
number = "2",

}

Brix, TH, Hansen, PS, Knudsen, GPS, Kringen, MK, Kyvik, KO, Orstavik, KH & Hegedüs, L 2009, 'No link between X chromosome inactivation pattern and simple goiter in females: evidence from a twin study', Thyroid, bind 19, nr. 2, s. 165-9. https://doi.org/10.1089/thy.2008.0380

No link between X chromosome inactivation pattern and simple goiter in females : evidence from a twin study. / Brix, Thomas Heiberg; Hansen, Pia Skov; Knudsen, Gun Peggy S; Kringen, Marianne K; Kyvik, Kirsten Ohm; Orstavik, Karen Helene; Hegedüs, Laszlo.

I: Thyroid, Bind 19, Nr. 2, 01.02.2009, s. 165-9.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskning

TY - JOUR

T1 - No link between X chromosome inactivation pattern and simple goiter in females

T2 - evidence from a twin study

AU - Brix, Thomas Heiberg

AU - Hansen, Pia Skov

AU - Knudsen, Gun Peggy S

AU - Kringen, Marianne K

AU - Kyvik, Kirsten Ohm

AU - Orstavik, Karen Helene

AU - Hegedüs, Laszlo

PY - 2009/2/1

Y1 - 2009/2/1

N2 - BACKGROUND: Simple goiter (SG) comprises diffuse (DG) and nodular (NG) benign nonautoimmune nontoxic goiter. In nonendemic goiter areas, the ratio of females to males may exceed 5:1, indicating that gender and/or sex hormones may play a role in the etiology of SG in these areas. Theoretically, as shown for autoimmune thyroid disease, X chromosome inactivation (XCI) and resultant tissue chimerism could offer a novel explanation for the female preponderance of SG. To examine whether skewed XCI is associated with SG, we first compared XCI in 71 twin individuals with SG with that in 142 unrelated healthy control twin individuals, and then performed a within-pair comparison of XCI in 48 twin pairs discordant for SG. METHODS: DNA was extracted from peripheral blood cells. XCI analysis was performed by predigestion of DNA using the methylation-sensitive enzyme Hpall, followed by polymerase chain reaction of the polymorphic CAG repeat of the androgen receptor gene. A polymerase chain reaction product is obtained from the inactive X chromosome only. The XCI pattern was classified as skewed when 80% or more of the cells preferentially inactivated the same X chromosome. Twin zygosity was established by DNA fingerprinting. RESULTS: The frequency of skewed XCI in female twins with SG, DG, and NG was 11% (8/71), 13% (6/46), and 8% (2/25), respectively, which was not significantly different from the prevalences in the corresponding control populations, 14% (20/142, p = 0.56), 14% (13/92, p = 1.00), and 14% (7/50, p = 0.71), respectively. Essentially, similar results were obtained when comparing the prevalence of skewed XCI in twin pairs discordant for SG (48 pairs), DG (30 pairs), and NG (18 pairs). CONCLUSION: In a sample of Danish female twins, we did not find evidence for involvement of skewed XCI in the etiology or the female preponderance of SG.

AB - BACKGROUND: Simple goiter (SG) comprises diffuse (DG) and nodular (NG) benign nonautoimmune nontoxic goiter. In nonendemic goiter areas, the ratio of females to males may exceed 5:1, indicating that gender and/or sex hormones may play a role in the etiology of SG in these areas. Theoretically, as shown for autoimmune thyroid disease, X chromosome inactivation (XCI) and resultant tissue chimerism could offer a novel explanation for the female preponderance of SG. To examine whether skewed XCI is associated with SG, we first compared XCI in 71 twin individuals with SG with that in 142 unrelated healthy control twin individuals, and then performed a within-pair comparison of XCI in 48 twin pairs discordant for SG. METHODS: DNA was extracted from peripheral blood cells. XCI analysis was performed by predigestion of DNA using the methylation-sensitive enzyme Hpall, followed by polymerase chain reaction of the polymorphic CAG repeat of the androgen receptor gene. A polymerase chain reaction product is obtained from the inactive X chromosome only. The XCI pattern was classified as skewed when 80% or more of the cells preferentially inactivated the same X chromosome. Twin zygosity was established by DNA fingerprinting. RESULTS: The frequency of skewed XCI in female twins with SG, DG, and NG was 11% (8/71), 13% (6/46), and 8% (2/25), respectively, which was not significantly different from the prevalences in the corresponding control populations, 14% (20/142, p = 0.56), 14% (13/92, p = 1.00), and 14% (7/50, p = 0.71), respectively. Essentially, similar results were obtained when comparing the prevalence of skewed XCI in twin pairs discordant for SG (48 pairs), DG (30 pairs), and NG (18 pairs). CONCLUSION: In a sample of Danish female twins, we did not find evidence for involvement of skewed XCI in the etiology or the female preponderance of SG.

U2 - 10.1089/thy.2008.0380

DO - 10.1089/thy.2008.0380

M3 - Journal article

VL - 19

SP - 165

EP - 169

JO - Thyroid

JF - Thyroid

SN - 1050-7256

IS - 2

ER -