Unexpected High Need for Genetic Testing in Rheumatology: A Cross-Sectional Cohort Study
Abstract
:1. Introduction
2. Patients and Methods
2.1. Study Design and Study Outcomes
2.2. Inclusion and Exclusion Criteria
2.3. Data Search
2.4. Statistical Analyses
3. Results
3.1. Diagnosis-Related Genetic Testing
3.2. Prognosis-Related Genetic Testing
3.3. Pharmacogenetic Testing
3.4. Comparisons of Potentially Needed and Performed Genetic Testing
3.5. Age-Specific Analyses
4. Discussion
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Appendix A
Main Diagnosis | Additional Diagnoses, Synonymes | |
---|---|---|
1 | Rheumatoid arthritis (RA) |
|
2 | Polymyalgia rheumatica ± large vessel arteritis (PMR/LVV), RS3PE |
|
3 | Axial spondyloarthritis (axSpA) |
|
4 | Peripheral spondyloarthritis (pSpA) |
|
5 | Collagenoses, other vasculitides (Coll./Vasc.) |
|
6 | Cristal diseases |
|
7 | Osteoarthritis, osteochondrosis |
|
8 | Non-inflammatory diseases |
|
9 | Other inflammatory diseases |
|
10 | Neoplastic diseases |
|
11 | Clinical and laboratory findings without diagnosis |
|
Drug | Trade Names |
---|---|
5-Fluorouracil | 5-Fluorouracil, Actikerall, Fluorouracil Accord, Tolak, Verrumal |
6-Mercaptopurine | Mercaptopurin Silver, Puri, Xaluprine |
Abacavir | Abacavir, Kivexa, Triumeq, Trizivir, Ziagen |
Acenocoumarol | Acenocoumarol, Sintrom |
Amitriptyline | Amitriptylin, Saroten |
Aripiprazol | Aripiprazol, Abilify, Arileto |
Atomoxetine | Atomoxetin, Atofab, Strattera |
Atorvastatin | Atorvastatin, Atorvilbitin, Atozet, Caduet, Callator, Ezeato, Sortis, Trinomia |
Azathioprine | Azathioprin, Azafalk, Immunoprin, Imurek, Jayempi |
Capecitabine | Capecel, Capecitabin, Ecansya, Xeloda |
Carbamazepine | Carbamazepin, Neurotop, Tegretol |
Citalopram | Citalopram, Citalostad, Pram, Seropram |
Clomipramine | Clomipramin, Anafranil, Clomicalm |
Clopidogrel | Aclop, Clopidogrel, DuoPlavin, Grepid, Iscover, Plavix, Zyllt |
Codeine | Codein, Resyl mit Codein |
Doxepin | not available |
Efavirenz | Efatriten, Efavirenz, Padviram, Stocrin, Sustiva |
Escitalopram | Cipralex, Escitalopram, Pramulex |
Estradiolvalerat | Progynova, Qlaira, Velbienne |
Ethinylestradiol | Aliane, Alisma, Balanca, Belara, Bellgyn, Gynial, Danselle, Danseo, Daylina, Delia, Desofemine, Diane mite, Dienorette, Dienovel, Drosfemine, Drospifem, Elione Erlidona, EVRA, FemLoop, Flow, Gefemin, GinoRing, Gracial, Gynovin, Harmonette, Lenea, Levostrol, Liberel, Loette, Madinette, Madonella, Marvelon, Mayra, Meliane, Melleva, Mercilon, Microgynon, Midane, Minesse, Minulet, Mirelle, Motion, MyRing, NuvaRing, Peliette, Rigevidon, Seasonique, Selma, SetLona, Sibilla, Solvetta, Triodena, Valette, Varianta, Viola, Volina, Wave, Xyliette, Yasmin, Yasminelle, YAZ, Yirala, Yris |
Flecianide | Amarhyton, Aristocor, Flecianid |
Flucloxacillin | Floxapen, Flucloxacillin |
Haloperidol | Haldol, Haloperidol |
Imipramine | not available |
Irinotecan | Irinotecan, Onivyde |
Lamotrigin | Gerolamic, Lamictal, Lamotrigin |
Metoprolol | Beloc, Lanoc, Metohexal, Metoprolol, Metoprolosuccinat, Seloken |
Nortriptyline | Nortrilen, Nortriptylin |
Oxcarbazepin | Trileptal, Oxcarbazepin |
Paroxetine | Ennos, Paroxat, Paroxetin, Seroxat |
Phenoprcoumon | Falithrom, Marcoumar, Phenoprocoumon |
Phenytoin | Epanutin, Epilan-D |
Pimozide | Orap, Pimozid |
Propafenone | Propafenon, Rytmonorma |
Rasburicase | Fasturtec, Rasburicase |
Sertraline | Adjuvin, Sertralin, Tresleen |
Simvastatin | Cholib, Ezesim, Simvastatin, Gerosim, Inegy, Nyzoc, SimEz, Simvastad, Simvatin, Zocord |
Tacrolimus | Adport, Advagraf, Dailiport, Envarsus, Modigraf, Prograf, Protopic, Tacforius, Tacni, Tacrolimus |
Tamoxifen | Ebefen, Nolvadex, Tamoxifen |
Tegafur | Teysuno, Tegafur |
Thioguanine | Thioguanin |
Tramadol | Adamon, Lanalget, Noax, Skudexa, Tradocomp, Tradolan, Tralieve, Tramabene, Tramadog, Tramadol, Tramadolhydrochlorid, Tramadolor, Tramal, Tramastad, Tramundal, Tramvetol, Zaldiar |
Venlafaxine | Efectin, Velostad, Venlafab, Venlafaxin |
Voriconazole | VFEND, Voriconazol, Voriconazole |
Warfarin | not available |
Zuclopenthixol | Cisordinol, Zuclopenthixol |
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Diagnostic Categories and Diagnoses | N [% of All] | Age [Years] | Sex [% Female] | Specific Lab Data [% of All Tests] |
---|---|---|---|---|
Inflammatory category | 1561 (62.7) | 58.2 | 63.1 | |
| 358 (14.4) | 63.7 | 72.3 | 65.0% ACPA+ |
| 333 (13.4) | 56.1 | 62.8 | 26.8% HLA-B27+ |
| 280 (11.2) | 51.5 | 56.8 | 61.4 % HLA-B27+ |
| 151 (6.1) | 74.2 | 52.3 | |
| 154 (6.2) | 52.7 | 77.9 | 70.2% ANA+, 22.5% ANCA+ |
| 83 (3.3) | 65.2 | 16.9 | |
| 202 (8.1) | 50.2 | 71.3 | |
Non-inflammatory category | 724 (29.1) | 54.9 | 74.6 | |
| 344 (13.8) | 62 | 77 | |
| 380 (15.3) | 48.5 | 72.4 | |
Neoplastic diseases | 13 (0.5) | 66.1 | 46.2 | |
Clinical and laboratory findings without diagnosis | 192 (7.7) | 51.4 | 68.8 |
Tests | Diagnoses | All Patients [% Patients] | Selected Patients [% Patients] |
---|---|---|---|
Frequent genes | |||
HLA-B testing | SpA/Behçet’s | 51.4 | 92.8 |
| SpA | 46.7 | 93.8 |
| Behçet’s | 2.9 | 80.0 |
Rare mutations | |||
MEVF | FMF | 0.4 | 100 |
NLRP3 | CAPS, FCAS, MWS, NOMID, CINCA syndrome | <0.1 | 100 |
NLRP12 | FCAS2 | <0.1 | 100 |
TNFRS1A | TRAPS | 0.1 | 100 |
CARD14 | CAMPS | <0.1 | 100 |
Genetic tests | 52.6% | 92.9% |
Drug | Number of Patients [n (% of Total)] | Pharmacogenetic Testing | Performed Tests [n (%)] |
---|---|---|---|
Atorvastatin | 168 (6.7) | SLCO1B1 | 0 |
AZA | 125 (5.0) | TPMT, NUDT15 | 93 (74.4), 0 |
Tramadol | 99 (4.0) | CYP2D6 | 0 |
Simvastatin | 83 (3.3) | SLCO1B1 | 0 |
Estradiolvalerat | 54 (2.2) | F5 | 0 |
Sertraline | 52 (2.1) | CYP2C19 | 0 |
Inflammatory [n (%)] | Non-Inflammatory [n (%)] | p | |
---|---|---|---|
Patients with potential need for genetic tests | 1204 (77.1) | 224 (24.1) | <0.001 |
| 656 (42.0) | 0 | |
| 358 (22.9) | 0 | |
| 473 (30.3) | 224 (24.1) | <0.001 |
| 174 (36.8) | 50 (22.3) | <0.001 |
| 354 (74.8) | 182 (81.3) | - |
Patients with performed genetic tests | 926 (59.3) | 406 (43.7) | <0.001 |
| 883 (56.6) | 403 (43.4) | <0.001 |
| 1 (0.1) | 1 (0.1) | |
| 84 (5.4) | 9 (1.0) | <0.001 |
| 84 (100) | 9 (100) | |
| 0 | 0 |
Total Cohort [n (%)] | 10 yrs <20 yrs [n (%)] | <30 yrs [n (%)] | <40 yrs [n (%)] | 40 yrs <50 yrs [n (%)] | <60 yrs [n (%)] | 60 yrs <70 yrs [n (%)] | 70 yrs <80 yrs [n (%)] | 80 yrs <90 yrs [n (%)] | 90 yrs [n (%)] | p | |
---|---|---|---|---|---|---|---|---|---|---|---|
Patients’ numbers, total | 2490 (100) | 7 | 186 | 219 | 342 | 627 | 522 | 378 | 195 | 14 | |
Patients with potential need for genetic testing | 1428 (57.3) | 4 (57.1) | 96 (51.6) | 116 (53.0) | 186 (54.4) | 349 (55.7) | 327 (62.6) | 223 (59.0) | 115 (59.0) | 12 (85.7) | |
| 1204 (77.1) | 4 (100) | 76 (79.2) | 95 (81.9) | 154 (82.8) | 302 (86.5) | 275 (84.1) | 187 (83.9) | 102 (88.7) | 9 (75.0) | * |
| 224 (24.1) | 0 (0) | 20 (20.8) | 21 (18.1) | 31 (16.7) | 47 (13.5) | 52 (15.9) | 36 (16.1) | 13 11.3) | 3 (25.0) | * |
Patients with performed genetic testing | 1332 (53.5) | 4 (57.1) | 122 (65.6) | 143 (65.3) | 217 (63.5) | 371 (59.2) | 270 (51.7) | 150 (39.7) | 53 (27.2) | 2 (14.3) | * |
| 926 (59.3) | 3 (75.0) | 88 (72.1) | 97 (67.8) | 141 (65.0) | 250 (67.4) | 193 (71.5) | 110 (73.3) | 42 (79.2) | 2 (100) | * |
| 406 (43.7) | 1 (25.0) | 34 (27.9) | 46 (32.2) | 76 (35.0) | 121 (32.6) | 77 (28.5) | 40 (26.7) | 11 (20.8) | 0 (0) | * |
Patients with performed out of potentially needed genetic testing | 93.2% | 100% | 127.1% | 123.3% | 116.7% | 106.3% | 82.6% | 67.3% | 46.1% | 16.7% | * |
| 76.9% | 75% | 115.8% | 102.1% | 91.6% | 82.8% | 70.2% | 58.8% | 41.2% | 22.2% | * |
| 181.3% | - | 170.0% | 219.0% | 245.2% | 257.4% | 148.1% | 111.1% | 84.6% | - | * |
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Share and Cite
Kampik, L.; Schirmer, M. Unexpected High Need for Genetic Testing in Rheumatology: A Cross-Sectional Cohort Study. Genes 2023, 14, 1858. https://doi.org/10.3390/genes14101858
Kampik L, Schirmer M. Unexpected High Need for Genetic Testing in Rheumatology: A Cross-Sectional Cohort Study. Genes. 2023; 14(10):1858. https://doi.org/10.3390/genes14101858
Chicago/Turabian StyleKampik, Lukas, and Michael Schirmer. 2023. "Unexpected High Need for Genetic Testing in Rheumatology: A Cross-Sectional Cohort Study" Genes 14, no. 10: 1858. https://doi.org/10.3390/genes14101858
APA StyleKampik, L., & Schirmer, M. (2023). Unexpected High Need for Genetic Testing in Rheumatology: A Cross-Sectional Cohort Study. Genes, 14(10), 1858. https://doi.org/10.3390/genes14101858