Genome-wide association study of high-sensitivity C-reactive protein, D-dimer and Interleukin-6 levels in multi-ethnic HIV+ cohorts

Forskning

Udskriv

Switch language

Region Hovedstaden - en del af Københavns Universitetshospital

Udgivet

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › peer review

Author

Sherman, Brad T ; Hu, Xiaojun ; Singh, Kanal ; Haine, Lillian ; Rupert, Adam W ; Neaton, James D ; Lundgren, Jens D ; Imamichi, Tomozumi ; Chang, Weizhong ; Lane, H Clifford ; ESPRIT, SMART and START Study Groups. / Genome-wide association study of high-sensitivity C-reactive protein, D-dimer and Interleukin-6 levels in multi-ethnic HIV+ cohorts. I: AIDS. 2021 ; Bind 35, Nr. 2. s. 193-204.

Bibtex

@article{93ed689017dd40ccbeaf0b91daf16762,

title = "Genome-wide association study of high-sensitivity C-reactive protein, D-dimer and Interleukin-6 levels in multi-ethnic HIV+ cohorts",

abstract = "OBJECTIVES: Elevated levels of interleukin-6 (IL-6), D-dimer, and C-reactive protein (hsCRP) are associated with increased incidence of comorbid disease and mortality among people living with HIV (PLWH). Prior studies suggest a genetic basis for these biomarker elevations in the general population. The study objectives are to identify the genetic basis for these biomarkers among PLWH.METHODS: Baseline levels of hsCRP, D-dimer, and IL-6, and single nucleotide polymorphisms (SNPs) were determined for 7768 participants in three HIV treatment trials. Single variant analysis was performed for each biomarker on samples from each of three ethnic groups [African (AFR), Admixed American (AMR), European (EUR)] within each trial including covariates relevant to biomarker levels. For each ethnic group, the results were pooled across trials, then further pooled across ethnicities.RESULTS: The transethnic analysis identified three, two, and one known loci associated with hsCRP, D-dimer, and IL-6 levels, respectively, and two novel loci, FGB and GCNT1, associated with D-dimer levels. Lead SNPs exhibited similar effects across ethnicities. Additionally, three novel, ethnic-specific loci were identified: CATSPERG associated with D-dimer in AFR and PROX1-AS1 and TRAPPC9 associated with IL-6 in AFR and AMR, respectively.CONCLUSION: Eleven loci associated with three biomarker levels were identified in PLWH from the three studies including six loci known in the general population and five novel loci associated with D-dimer and IL-6 levels. These findings support the hypothesis that host genetics may partially contribute to chronic inflammation in PLWH and help to identify potential targets for intervention of serious non-AIDS complications.",

author = "Sherman, {Brad T} and Xiaojun Hu and Kanal Singh and Lillian Haine and Rupert, {Adam W} and Neaton, {James D} and Lundgren, {Jens D} and Tomozumi Imamichi and Weizhong Chang and Lane, {H Clifford} and {ESPRIT, SMART and START Study Groups}",

note = "Copyright {\circledC} 2020 The Author(s). Published by Wolters Kluwer Health, Inc.",

year = "2021",

month = "2",

day = "2",

doi = "10.1097/QAD.0000000000002738",

language = "English",

volume = "35",

pages = "193--204",

journal = "AIDS",

issn = "0269-9370",

publisher = "Lippincott Williams & Wilkins",

number = "2",

}

RIS

TY - JOUR

T1 - Genome-wide association study of high-sensitivity C-reactive protein, D-dimer and Interleukin-6 levels in multi-ethnic HIV+ cohorts

AU - Sherman, Brad T

AU - Hu, Xiaojun

AU - Singh, Kanal

AU - Haine, Lillian

AU - Rupert, Adam W

AU - Neaton, James D

AU - Lundgren, Jens D

AU - Imamichi, Tomozumi

AU - Chang, Weizhong

AU - Lane, H Clifford

AU - ESPRIT, SMART and START Study Groups

PY - 2021/2/2

Y1 - 2021/2/2

N2 - OBJECTIVES: Elevated levels of interleukin-6 (IL-6), D-dimer, and C-reactive protein (hsCRP) are associated with increased incidence of comorbid disease and mortality among people living with HIV (PLWH). Prior studies suggest a genetic basis for these biomarker elevations in the general population. The study objectives are to identify the genetic basis for these biomarkers among PLWH.METHODS: Baseline levels of hsCRP, D-dimer, and IL-6, and single nucleotide polymorphisms (SNPs) were determined for 7768 participants in three HIV treatment trials. Single variant analysis was performed for each biomarker on samples from each of three ethnic groups [African (AFR), Admixed American (AMR), European (EUR)] within each trial including covariates relevant to biomarker levels. For each ethnic group, the results were pooled across trials, then further pooled across ethnicities.RESULTS: The transethnic analysis identified three, two, and one known loci associated with hsCRP, D-dimer, and IL-6 levels, respectively, and two novel loci, FGB and GCNT1, associated with D-dimer levels. Lead SNPs exhibited similar effects across ethnicities. Additionally, three novel, ethnic-specific loci were identified: CATSPERG associated with D-dimer in AFR and PROX1-AS1 and TRAPPC9 associated with IL-6 in AFR and AMR, respectively.CONCLUSION: Eleven loci associated with three biomarker levels were identified in PLWH from the three studies including six loci known in the general population and five novel loci associated with D-dimer and IL-6 levels. These findings support the hypothesis that host genetics may partially contribute to chronic inflammation in PLWH and help to identify potential targets for intervention of serious non-AIDS complications.

AB - OBJECTIVES: Elevated levels of interleukin-6 (IL-6), D-dimer, and C-reactive protein (hsCRP) are associated with increased incidence of comorbid disease and mortality among people living with HIV (PLWH). Prior studies suggest a genetic basis for these biomarker elevations in the general population. The study objectives are to identify the genetic basis for these biomarkers among PLWH.METHODS: Baseline levels of hsCRP, D-dimer, and IL-6, and single nucleotide polymorphisms (SNPs) were determined for 7768 participants in three HIV treatment trials. Single variant analysis was performed for each biomarker on samples from each of three ethnic groups [African (AFR), Admixed American (AMR), European (EUR)] within each trial including covariates relevant to biomarker levels. For each ethnic group, the results were pooled across trials, then further pooled across ethnicities.RESULTS: The transethnic analysis identified three, two, and one known loci associated with hsCRP, D-dimer, and IL-6 levels, respectively, and two novel loci, FGB and GCNT1, associated with D-dimer levels. Lead SNPs exhibited similar effects across ethnicities. Additionally, three novel, ethnic-specific loci were identified: CATSPERG associated with D-dimer in AFR and PROX1-AS1 and TRAPPC9 associated with IL-6 in AFR and AMR, respectively.CONCLUSION: Eleven loci associated with three biomarker levels were identified in PLWH from the three studies including six loci known in the general population and five novel loci associated with D-dimer and IL-6 levels. These findings support the hypothesis that host genetics may partially contribute to chronic inflammation in PLWH and help to identify potential targets for intervention of serious non-AIDS complications.

U2 - 10.1097/QAD.0000000000002738

DO - 10.1097/QAD.0000000000002738

M3 - Journal article

VL - 35

SP - 193

EP - 204

JO - AIDS

JF - AIDS

SN - 0269-9370

IS - 2

ER -

ID: 61098331