A common missense variant of LILRB5 is associated with statin intolerance

A GoDARTS study

M. K. Siddiqui, A. Veluchamy, R. Tavendale, F. Carr, C. Maroteau, E. R. Pearson, H. M. Looker, A. D. Morris, E. Dow, J. George, A. Doney, C. N. A. Palmer (Lead / Corresponding author)

Research output: Contribution to conferencePoster

Abstract

There are approximately 12 million statin users in the United Kingdom. Approximately 9% of users present with intolerance to statins, manifesting as muscle ache, fatigue or more seriously, muscle breakdown leading to myopathy. Creatine phosphokinase (CK) levels are used as a biomarker of statin-induced muscle damage. Variants in LILRB5 and CKM were shown to be associated with CK levels irrespective of statin usage. This study aims to analyse the association of these variants with statin intolerance.Genotype information was gathered for two missense variants, rs12975366 (LILRB5: Asp247Gly) and rs11559024 (CKM: Glu83Gly) in the GoDARTS study cohort of Scottish Caucasian individuals in the Tayside and Fife areas. We found both variants were associated with CK levels in statin users and non-users, but that only Asp247Gly was associated with our definition of statin intolerance (raised CK and accompanying prescribing changes) : OR 0.48, p value 7.7 x 10 ⁻⁵ and 95% CI (0.28, 0.65).This demonstrates that the LILRB5 locus is associated with statin intolerance-related raised CK levels, whereas CKM is purely a marker of constitutional serum CK levels. This study also highlights the probability that statin intolerant individuals may not have raised CK levels for genetic reasons.This study presents a novel genetic factor associated with statin intolerance and raises considerations for the usage of CK as a biomarker. It encourages further investigation into the physiology of statin-induced muscle damage, inter-individual variability in CK levels and response to muscle damage.
Original languageEnglish
Publication statusPublished - 6 Oct 2015
Event65th American Society of Human Genetics Annual Meeting - Baltimore Convention Center, Baltimore, United States
Duration: 6 Oct 201510 Oct 2015
http://www.ashg.org/2015meeting/ (Link to Conference website)

Conference

Conference65th American Society of Human Genetics Annual Meeting
Abbreviated titleASHG 2015
CountryUnited States
CityBaltimore
Period6/10/1510/10/15
Internet address

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Hydroxymethylglutaryl-CoA Reductase Inhibitors
Muscles
Biomarkers
Muscle Fatigue
Muscular Diseases
Creatine Kinase
Cohort Studies
Genotype

Keywords

  • Pharmacogenetics
  • Immunogenetics
  • Epidemiology

Cite this

Siddiqui, M. K., Veluchamy, A., Tavendale, R., Carr, F., Maroteau, C., Pearson, E. R., ... Palmer, C. N. A. (2015). A common missense variant of LILRB5 is associated with statin intolerance: A GoDARTS study. Poster session presented at 65th American Society of Human Genetics Annual Meeting, Baltimore, United States.
Siddiqui, M. K. ; Veluchamy, A. ; Tavendale, R. ; Carr, F. ; Maroteau, C. ; Pearson, E. R. ; Looker, H. M. ; Morris, A. D. ; Dow, E. ; George, J. ; Doney, A. ; Palmer, C. N. A. / A common missense variant of LILRB5 is associated with statin intolerance : A GoDARTS study. Poster session presented at 65th American Society of Human Genetics Annual Meeting, Baltimore, United States.
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abstract = "There are approximately 12 million statin users in the United Kingdom. Approximately 9{\%} of users present with intolerance to statins, manifesting as muscle ache, fatigue or more seriously, muscle breakdown leading to myopathy. Creatine phosphokinase (CK) levels are used as a biomarker of statin-induced muscle damage. Variants in LILRB5 and CKM were shown to be associated with CK levels irrespective of statin usage. This study aims to analyse the association of these variants with statin intolerance.Genotype information was gathered for two missense variants, rs12975366 (LILRB5: Asp247Gly) and rs11559024 (CKM: Glu83Gly) in the GoDARTS study cohort of Scottish Caucasian individuals in the Tayside and Fife areas. We found both variants were associated with CK levels in statin users and non-users, but that only Asp247Gly was associated with our definition of statin intolerance (raised CK and accompanying prescribing changes) : OR 0.48, p value 7.7 x 10 ⁻⁵ and 95{\%} CI (0.28, 0.65).This demonstrates that the LILRB5 locus is associated with statin intolerance-related raised CK levels, whereas CKM is purely a marker of constitutional serum CK levels. This study also highlights the probability that statin intolerant individuals may not have raised CK levels for genetic reasons.This study presents a novel genetic factor associated with statin intolerance and raises considerations for the usage of CK as a biomarker. It encourages further investigation into the physiology of statin-induced muscle damage, inter-individual variability in CK levels and response to muscle damage.",
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Siddiqui, MK, Veluchamy, A, Tavendale, R, Carr, F, Maroteau, C, Pearson, ER, Looker, HM, Morris, AD, Dow, E, George, J, Doney, A & Palmer, CNA 2015, 'A common missense variant of LILRB5 is associated with statin intolerance: A GoDARTS study' 65th American Society of Human Genetics Annual Meeting, Baltimore, United States, 6/10/15 - 10/10/15, .

A common missense variant of LILRB5 is associated with statin intolerance : A GoDARTS study. / Siddiqui, M. K.; Veluchamy, A.; Tavendale, R.; Carr, F.; Maroteau, C.; Pearson, E. R.; Looker, H. M.; Morris, A. D.; Dow, E.; George, J.; Doney, A.; Palmer, C. N. A. (Lead / Corresponding author).

2015. Poster session presented at 65th American Society of Human Genetics Annual Meeting, Baltimore, United States.

Research output: Contribution to conferencePoster

TY - CONF

T1 - A common missense variant of LILRB5 is associated with statin intolerance

T2 - A GoDARTS study

AU - Siddiqui, M. K.

AU - Veluchamy, A.

AU - Tavendale, R.

AU - Carr, F.

AU - Maroteau, C.

AU - Pearson, E. R.

AU - Looker, H. M.

AU - Morris, A. D.

AU - Dow, E.

AU - George, J.

AU - Doney, A.

AU - Palmer, C. N. A.

N1 - Pharmacogenetics Poster Session 662W

PY - 2015/10/6

Y1 - 2015/10/6

N2 - There are approximately 12 million statin users in the United Kingdom. Approximately 9% of users present with intolerance to statins, manifesting as muscle ache, fatigue or more seriously, muscle breakdown leading to myopathy. Creatine phosphokinase (CK) levels are used as a biomarker of statin-induced muscle damage. Variants in LILRB5 and CKM were shown to be associated with CK levels irrespective of statin usage. This study aims to analyse the association of these variants with statin intolerance.Genotype information was gathered for two missense variants, rs12975366 (LILRB5: Asp247Gly) and rs11559024 (CKM: Glu83Gly) in the GoDARTS study cohort of Scottish Caucasian individuals in the Tayside and Fife areas. We found both variants were associated with CK levels in statin users and non-users, but that only Asp247Gly was associated with our definition of statin intolerance (raised CK and accompanying prescribing changes) : OR 0.48, p value 7.7 x 10 ⁻⁵ and 95% CI (0.28, 0.65).This demonstrates that the LILRB5 locus is associated with statin intolerance-related raised CK levels, whereas CKM is purely a marker of constitutional serum CK levels. This study also highlights the probability that statin intolerant individuals may not have raised CK levels for genetic reasons.This study presents a novel genetic factor associated with statin intolerance and raises considerations for the usage of CK as a biomarker. It encourages further investigation into the physiology of statin-induced muscle damage, inter-individual variability in CK levels and response to muscle damage.

AB - There are approximately 12 million statin users in the United Kingdom. Approximately 9% of users present with intolerance to statins, manifesting as muscle ache, fatigue or more seriously, muscle breakdown leading to myopathy. Creatine phosphokinase (CK) levels are used as a biomarker of statin-induced muscle damage. Variants in LILRB5 and CKM were shown to be associated with CK levels irrespective of statin usage. This study aims to analyse the association of these variants with statin intolerance.Genotype information was gathered for two missense variants, rs12975366 (LILRB5: Asp247Gly) and rs11559024 (CKM: Glu83Gly) in the GoDARTS study cohort of Scottish Caucasian individuals in the Tayside and Fife areas. We found both variants were associated with CK levels in statin users and non-users, but that only Asp247Gly was associated with our definition of statin intolerance (raised CK and accompanying prescribing changes) : OR 0.48, p value 7.7 x 10 ⁻⁵ and 95% CI (0.28, 0.65).This demonstrates that the LILRB5 locus is associated with statin intolerance-related raised CK levels, whereas CKM is purely a marker of constitutional serum CK levels. This study also highlights the probability that statin intolerant individuals may not have raised CK levels for genetic reasons.This study presents a novel genetic factor associated with statin intolerance and raises considerations for the usage of CK as a biomarker. It encourages further investigation into the physiology of statin-induced muscle damage, inter-individual variability in CK levels and response to muscle damage.

KW - Pharmacogenetics

KW - Immunogenetics

KW - Epidemiology

UR - http://www.ashg.org/2015meeting/pages/posterlisting.shtml

UR - http://www.ashg.org/2015meeting/

M3 - Poster

ER -

Siddiqui MK, Veluchamy A, Tavendale R, Carr F, Maroteau C, Pearson ER et al. A common missense variant of LILRB5 is associated with statin intolerance: A GoDARTS study. 2015. Poster session presented at 65th American Society of Human Genetics Annual Meeting, Baltimore, United States.