Short QTc Interval in Males with Klinefelter Syndrome: Influence of CAG Repeat Length, Body Composition, and Testosterone Replacement Therapy

I. N. Jorgensen, A. Skakkebæk, N. H. Andersen, L. N. Pedersen, D. M. Hougaard, A. Bojesen, C. Trolle, C. H. Gravholt

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Resumé

BackgroundKlinefelter syndrome (KS) is a sex chromosomal aneuploidy (47,XXY) affecting 1/660 males. Based on findings in Turner syndrome, we hypothesized that electrocardiogram (ECG) abnormalities would be present in males with KS. ObjectiveTo investigate ECGs in males with KS and compare with controls. MethodsCase control study of 62 males with KS and 62 healthy males matched on age. The primary outcome parameter was a difference in the ECG presentation between the two groups. The ECGs were analyzed by one blinded examiner (intraobserver variability 0.2-2.1%). The QT-interval was measured using teach-the-tangent method excluding the U-wave. QTc was calculated using Bazett's equation, Hodges' equation, and a linear regression model. Body mass index, abdominal fat, and muscle mass as well as sex hormone levels were secondary parameters. The prevalence of mutations in genes related to short QT syndrome was determined in participants with a QTc <330 ms. ResultsCompared to controls, the QTc-interval was shorter (P = 0.02-0.06) in males with KS depending on the applied correction method. QTc was shortest among testosterone (T)-treated males with KS, while untreated and thus hypogonadal KS had QTc interval comparable to controls. No mutations in genes related to short QT syndrome were found. ConclusionWe found short QTc interval in males with KS, with further shortening of the QTc interval by T. These results suggest that genes on the X chromosome could be involved in regulation of the QTc interval and that T treatment may aggravate this mechanism.
OriginalsprogEngelsk
TidsskriftPacing and Clinical Electrophysiology
Vol/bind38
Udgave nummer4
Sider (fra-til)472-482
ISSN0147-8389
DOI
StatusUdgivet - 2015

Bibliografisk note

Lundbeck foundation; Augustinus Foundation; Aase and Einar Danielsen Foundation; University of Aarhus; Novo Nordisk Foundation 3 25615644

Emneord

  • body composition hypothalamus-pituitary-testicular axis hypogonadism cardiology ECG ANDROGEN RECEPTOR POLYMORPHISM X-CHROMOSOME INACTIVATION HEART-RATE MORTALITY PREVALENCE PHENOTYPE HORMONES MEN AGE

Citer dette

Jorgensen, I. N. ; Skakkebæk, A. ; Andersen, N. H. ; Pedersen, L. N. ; Hougaard, D. M. ; Bojesen, A. ; Trolle, C. ; Gravholt, C. H. / Short QTc Interval in Males with Klinefelter Syndrome : Influence of CAG Repeat Length, Body Composition, and Testosterone Replacement Therapy. I: Pacing and Clinical Electrophysiology. 2015 ; Bind 38, Nr. 4. s. 472-482.
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title = "Short QTc Interval in Males with Klinefelter Syndrome: Influence of CAG Repeat Length, Body Composition, and Testosterone Replacement Therapy",
abstract = "BackgroundKlinefelter syndrome (KS) is a sex chromosomal aneuploidy (47,XXY) affecting 1/660 males. Based on findings in Turner syndrome, we hypothesized that electrocardiogram (ECG) abnormalities would be present in males with KS. ObjectiveTo investigate ECGs in males with KS and compare with controls. MethodsCase control study of 62 males with KS and 62 healthy males matched on age. The primary outcome parameter was a difference in the ECG presentation between the two groups. The ECGs were analyzed by one blinded examiner (intraobserver variability 0.2-2.1{\%}). The QT-interval was measured using teach-the-tangent method excluding the U-wave. QTc was calculated using Bazett's equation, Hodges' equation, and a linear regression model. Body mass index, abdominal fat, and muscle mass as well as sex hormone levels were secondary parameters. The prevalence of mutations in genes related to short QT syndrome was determined in participants with a QTc <330 ms. ResultsCompared to controls, the QTc-interval was shorter (P = 0.02-0.06) in males with KS depending on the applied correction method. QTc was shortest among testosterone (T)-treated males with KS, while untreated and thus hypogonadal KS had QTc interval comparable to controls. No mutations in genes related to short QT syndrome were found. ConclusionWe found short QTc interval in males with KS, with further shortening of the QTc interval by T. These results suggest that genes on the X chromosome could be involved in regulation of the QTc interval and that T treatment may aggravate this mechanism.",
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author = "Jorgensen, {I. N.} and A. Skakkeb{\ae}k and Andersen, {N. H.} and Pedersen, {L. N.} and Hougaard, {D. M.} and A. Bojesen and C. Trolle and Gravholt, {C. H.}",
note = "Lundbeck foundation; Augustinus Foundation; Aase and Einar Danielsen Foundation; University of Aarhus; Novo Nordisk Foundation 3 25615644",
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Short QTc Interval in Males with Klinefelter Syndrome : Influence of CAG Repeat Length, Body Composition, and Testosterone Replacement Therapy. / Jorgensen, I. N.; Skakkebæk, A.; Andersen, N. H.; Pedersen, L. N.; Hougaard, D. M.; Bojesen, A.; Trolle, C.; Gravholt, C. H.

I: Pacing and Clinical Electrophysiology, Bind 38, Nr. 4, 2015, s. 472-482.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

TY - JOUR

T1 - Short QTc Interval in Males with Klinefelter Syndrome

T2 - Influence of CAG Repeat Length, Body Composition, and Testosterone Replacement Therapy

AU - Jorgensen, I. N.

AU - Skakkebæk, A.

AU - Andersen, N. H.

AU - Pedersen, L. N.

AU - Hougaard, D. M.

AU - Bojesen, A.

AU - Trolle, C.

AU - Gravholt, C. H.

N1 - Lundbeck foundation; Augustinus Foundation; Aase and Einar Danielsen Foundation; University of Aarhus; Novo Nordisk Foundation 3 25615644

PY - 2015

Y1 - 2015

N2 - BackgroundKlinefelter syndrome (KS) is a sex chromosomal aneuploidy (47,XXY) affecting 1/660 males. Based on findings in Turner syndrome, we hypothesized that electrocardiogram (ECG) abnormalities would be present in males with KS. ObjectiveTo investigate ECGs in males with KS and compare with controls. MethodsCase control study of 62 males with KS and 62 healthy males matched on age. The primary outcome parameter was a difference in the ECG presentation between the two groups. The ECGs were analyzed by one blinded examiner (intraobserver variability 0.2-2.1%). The QT-interval was measured using teach-the-tangent method excluding the U-wave. QTc was calculated using Bazett's equation, Hodges' equation, and a linear regression model. Body mass index, abdominal fat, and muscle mass as well as sex hormone levels were secondary parameters. The prevalence of mutations in genes related to short QT syndrome was determined in participants with a QTc <330 ms. ResultsCompared to controls, the QTc-interval was shorter (P = 0.02-0.06) in males with KS depending on the applied correction method. QTc was shortest among testosterone (T)-treated males with KS, while untreated and thus hypogonadal KS had QTc interval comparable to controls. No mutations in genes related to short QT syndrome were found. ConclusionWe found short QTc interval in males with KS, with further shortening of the QTc interval by T. These results suggest that genes on the X chromosome could be involved in regulation of the QTc interval and that T treatment may aggravate this mechanism.

AB - BackgroundKlinefelter syndrome (KS) is a sex chromosomal aneuploidy (47,XXY) affecting 1/660 males. Based on findings in Turner syndrome, we hypothesized that electrocardiogram (ECG) abnormalities would be present in males with KS. ObjectiveTo investigate ECGs in males with KS and compare with controls. MethodsCase control study of 62 males with KS and 62 healthy males matched on age. The primary outcome parameter was a difference in the ECG presentation between the two groups. The ECGs were analyzed by one blinded examiner (intraobserver variability 0.2-2.1%). The QT-interval was measured using teach-the-tangent method excluding the U-wave. QTc was calculated using Bazett's equation, Hodges' equation, and a linear regression model. Body mass index, abdominal fat, and muscle mass as well as sex hormone levels were secondary parameters. The prevalence of mutations in genes related to short QT syndrome was determined in participants with a QTc <330 ms. ResultsCompared to controls, the QTc-interval was shorter (P = 0.02-0.06) in males with KS depending on the applied correction method. QTc was shortest among testosterone (T)-treated males with KS, while untreated and thus hypogonadal KS had QTc interval comparable to controls. No mutations in genes related to short QT syndrome were found. ConclusionWe found short QTc interval in males with KS, with further shortening of the QTc interval by T. These results suggest that genes on the X chromosome could be involved in regulation of the QTc interval and that T treatment may aggravate this mechanism.

KW - body composition hypothalamus-pituitary-testicular axis hypogonadism cardiology ECG ANDROGEN RECEPTOR POLYMORPHISM X-CHROMOSOME INACTIVATION HEART-RATE MORTALITY PREVALENCE PHENOTYPE HORMONES MEN AGE

U2 - 10.1111/pace.12580

DO - 10.1111/pace.12580

M3 - Journal article

C2 - 25615644

VL - 38

SP - 472

EP - 482

JO - Pacing and Clinical Electrophysiology

JF - Pacing and Clinical Electrophysiology

SN - 0147-8389

IS - 4

ER -