Alpha1-antitrypsin deficiency in Greece: Focus on rare variants

被引：6

作者：

Papiris, S. A. ^{[1
]}

Veith, M. ^{[2
,3
]}

Papaioannou, A. I. ^{[1
]}

Apollonatou, V. ^{[1
]}

Ferrarotti, I. ^{[4
]}

Ottaviani, S. ^{[4
]}

Tzouvelekis, A. ^{[5
]}

Tzilas, V. ^{[6
]}

Rovina, N. ^{[7
,8
]}

Stratakos, G. ^{[9
]}

Gerogianni, I. ^{[10
]}

Daniil, Z. ^{[10
]}

Kolilekas, L. ^{[11
]}

Dimakou, K. ^{[6
]}

Pitsidianakis, G. ^{[12
]}

Tzanakis, N. ^{[12
]}

Tryfon, S. ^{[13
]}

Fragopoulos, F. ^{[14
]}

Antonogiannaki, E. M. ^{[15
]}

Lazaratou, A. ^{[1
]}

Fouka, E. ^{[16
]}

Papakosta, D. ^{[16
]}

Emmanouil, P. ^{[17
]}

Anagnostopoulos, N. ^{[7
,14
]}

Karampitsakos, T. ^{[5
]}

Vlami, K. ^{[1
]}

Kallieri, M. ^{[1
]}

Lyberopoulos, P. ^{[1
]}

Loukides, S. ^{[1
]}

Bouros, D. ^{[18
,19
]}

Bush, A. ^{[20
]}

Balduyck, M. ^{[21
,22
]}

Lombard, C. ^{[23
,24
]}

Cottin, V. ^{[25
]}

Mornex, J. F. ^{[25
]}

Vogelmeier, C. F. ^{[2
,3
]}

Greulich, T. ^{[2
,3
]}

Manali, E. D. ^{[1
]}

机构：

[1] Natl & Kapodistrian Univ Athens, Gen Univ Hosp Attikon, Med Sch, Pulm Med Dept 2, Greece 1 Rimini St, Haidari 12462, Greece

[2] UKGM, Dept Med Pulm & Crit Care Med, Marburg, Germany

[3] UKGM, German Ctr Lung Res DZL, Marburg, Germany

[4] Univ Pavia, Fdn IRCCS Policlin San Matteo, Ctr Diag Inherited Alpha1 Antitrypsin Deficiency, Dept Internal Med & Therapeut,Pneumonol Unit, Pavia, Italy

[5] Univ Patras, Gen Hosp Patras, Dept Resp Med, Patras, Greece

[6] Athens Chest Hosp Sotiria, Pulm Dept 5, Athens, Greece

[7] Natl & Kapodistrian Univ, Med Sch, Dept Pulm Med 1, Athens 11527, Greece

[8] Natl & Kapodistrian Univ, Med Sch, Intens Care Unit, Athens 11527, Greece

[9] Kapodistrian Univ Athens, Resp Med Dept Natl 1, Athens, Greece

[10] Univ Thessaly, Fac Med, Sch Hlth Sci, Dept Resp Med, Larisa, Greece

[11] Athens Chest Hosp Sotiria, Dept 7thPulm, Athens, Greece

[12] Univ Hosp, Univ Crete, Dept Thorac Med, Iraklion 71110, Crete, Greece

[13] Gen Hosp G Papanikolaou, Thessaloniki, Greece

[14] Gen Hosp Nicosia, Pulm Dept, Strovolos, Cyprus

[15] Athens Chest Hosp Sotiria, Pulm Dept 4, Athens, Greece

[16] Aristotle Univ Thessaloniki, G Papanikolaou Hosp, Dept Pulm Med A, Thessaloniki, Greece

[17] Mediterraneo Hosp, Glifadha, Greece

[18] Iatriko Med Ctr, Athens, Greece

[19] Natl & Kapodistrian Univ Athens, Sch Med, Athens, Greece

[20] Royal Brompton Harefield NHS Fdn Trust, Imperial Coll, Imperial Ctr Paediat & Child Hlth, Paediat & Paediat Respirol, London, England

[21] Univ Lille, Fac Pharm, Ctr Biol Pathol, Lab Biochim & Biol Mol HMNO,CHU Lille, Lille, France

[22] Univ Lille, EA RADEME 7364, Lab Biochim & Biol Mol, CHU Lille, Lille, France

[23] Ctr Hosp Lyon Sud, Lab Immunol, Hosp Civils Lyon, Lyon, France

[24] Univ Claude Bernard Lyon 1, Lyon, France

[25] Univ Lyon, Univ Claude Bernard Lyon 1, Hop Louis Pradel, Hop Louis Pradel,Serv Pneumol,Hosp Civils Lyon,UMR, Lyon, France

来源：

PULMONOLOGY | 2024年 / 30卷 / 01期

关键词：

A(1)antitrypsin; Rare variants; Emphysema; Genetic diversity; Gene sequencing; Greeks; OBSTRUCTIVE PULMONARY-DISEASE; QUALITY-OF-LIFE; PI-ASTERISK-SZ; ALPHA-1-ANTITRYPSIN DEFICIENCY; MOLECULAR CHARACTERIZATION; ALPHA(1)-ANTITRYPSIN; GENE; REGISTRY; ALLELES; MUTATION;

D O I：

10.1016/j.pulmoe.2022.12.007

中图分类号：

R56 [呼吸系及胸部疾病];

学科分类号：

摘要：

Purpose: A(1)Antitrypsin deficiency (AATD) pathogenic mutations are expanding beyond the PI*Z and PI*S to a multitude of rare variants. Aim: to investigate genotype and clinical profile of Greeks with AATD. Methods: Symptomatic adult-patients with early-emphysema defined by fixed airway obstruction and computerized-tomography scan and lower than normal serum AAT levels were enrolled from reference centers all over Greece. Samples were analyzed in the AAT Laboratory, University of Marburg-Germany. Results: Included are 45 adults, 38 homozygous or compound heterozygous for pathogenic variants and 7 heterozygous. Homozygous were 57.9% male, 65.8% ever-smokers, median (IQR) age 49.0(42.5-58.5) years, AAT-levels 0.20(0.08-0.26) g/L, FEV1(%predicted) 41.5(28.8-64.5). PI*Z, PI*Q0, and rare deficient allele's frequency was 51.3%, 32.9%,15.8%, respectively. PI*ZZ genotype was 36.8%, PI*Q0Q0 21.1%, PI*MdeficientMdeficient 7.9%, PI*ZQ0 18.4%, PI*Q0Mdeficient 5.3% and PI*Zrare-deficient 10.5%. Genotyping by Luminex detected: p.(Pro393Leu) associated with M-Heerlen (M1Ala/M1Val); p.(Leu65Pro) with M-Procida; p.(Lys241Ter) with Q0(Bellingham); p.(Leu377Phefs*24) with Q0(Mattawa) (M1Val) and Q0(Ourem) (M3); p.(Phe76del) with M-Malton (M2), M-Palermo (M1Val), M-Nichinan (V) and Q0(LaPalma) (S); p.(Asp280Val) with P-Lowell (M1Val)(;) P-Duarte (M4)(,) Y-Barcelona (p.Pro39His). Gene-sequencing (46.7%) detected Q0(GraniteFalls), Q0(Saint-Etienne), Q0(Amersfoort(M1Ala),) M-W & uuml;rzburg, N-Hartfordcity and one novel-variant (c.1A>G) named Q0(Attikon).Heterozygous included PI*MQ0(Amersfoort(M1Ala),) PI*MMProcida, PI*Mp.(Asp280Val), PI*MOFeyzin. AAT-levels were significantly different between genotypes (p = 0.002). Conclusion: Genotyping AATD in Greece, a multiplicity of rare variants and a diversity of rare combinations, including unique ones were observed in two thirds of patients, expanding knowledge regarding European geographical trend in rare variants. Gene sequencing was necessary for genetic diagnosis. In the future the detection of rare genotypes may add to personalize preventive and therapeutic measures. (c) 2023 Sociedade Portuguesa de Pneumologia. Published by Elsevier Esparta, S.L.U. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

引用

页码：43 / 52

页数：10

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