results.txt

Create a knowledge graph of rs113993960 using the following abstracts: 
1. Eur Respir J. 2020 Sep 10;56(3):2000558. doi: 10.1183/13993003.00558-2020.
Print  2020 Sep.

Morbidity and mortality in carriers of the cystic fibrosis mutation CFTR 
Phe508del in the general population.

Çolak Y(1)(2)(3), Nordestgaard BG(1)(2)(3), Afzal S(1)(2)(3).

Author information:
(1)Dept of Clinical Biochemistry, Herlev and Gentofte Hospital, Copenhagen 
University Hospital, Herlev, Denmark.
(2)The Copenhagen General Population Study, Herlev and Gentofte Hospital, 
Copenhagen University Hospital, Herlev, Denmark.
(3)Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, 
Denmark.

Comment in
    Eur Respir J. 2020 Sep 10;56(3):

Cystic fibrosis (CF) is caused by autosomal-recessive inheritance of a 
dysfunctional cystic fibrosis transmembrane conductance regulator (CFTR), up to 
90% due to Phe508del mutation in the CFTR gene. We tested the hypothesis that 
CFTR Phe508del carriers have increased morbidity and mortality versus 
non-carriers in the general population.We genotyped 108 035 randomly selected 
white Danish individuals from the Copenhagen General Population Study (aged from 
20-100 years) for CFTR Phe508del mutation (rs113993960). Risk of chronic 
bronchitis and airflow limitation was assessed cross-sectionally. Overall 
survival and risk of bronchiectasis, lung cancer, pneumonia, chronic 
rhinosinusitis, airway bleeding, spontaneous pneumothorax, respiratory failure, 
acute and chronic pancreatitis, liver cirrhosis, ileus, gastric and colorectal 
cancer, and male infertility were assessed prospectively during up to 15 years 
of follow-up (median: 9 years). A single individual was excluded due to 
homozygosity for CFTR Phe508del and known CF. No other individuals had diagnosed 
CF at baseline examination or during follow-up.Among the resulting 108 034 
individuals, 105 176 (97%) were non-carriers and 2858 (3%) were carriers (i.e. 
were heterozygous for CFTR Phe508del). Overall survival was similar between 
carriers and non-carriers. Compared to non-carriers and with multivariable 
adjustment, carriers had an odds ratio (OR) of 1.31 (95% CI 1.16-1.48) for 
chronic bronchitis, a hazard ratio (HR) of 1.88 (95% CI 1.03-3.45) for 
bronchiectasis and 1.52 (95% CI 1.12-2.08) for lung cancer. Carriers did not 
differ from non-carriers concerning lung function or any other morbidity 
outcomes as mentioned above.In the general population, carriers of CFTR 
Phe508del have a normal lifespan but an increased risk of chronic bronchitis 
(1.3-fold), bronchiectasis (1.9-fold) and lung cancer (1.5-fold).

Copyright ©ERS 2020.

DOI: 10.1183/13993003.00558-2020
PMID: 32398304 [Indexed for MEDLINE]

Conflict of interest statement: Conflict of interest: B.G. Nordestgaard has 
nothing to disclose. Conflict of interest: S. Afzal has nothing to disclose. 
Conflict of interest: Y. Çolak reports personal fees from Boehringer Ingelheim, 
AstraZeneca and Sanofi Genzyme, outside the submitted work.


2. Pharmgenomics Pers Med. 2020 Dec 1;13:679-686. doi: 10.2147/PGPM.S278806. 
eCollection 2020.

Cystic Fibrosis Polymorphic Variants in a Russian Population.

Kiseleva A(#)(1), Klimushina M(#)(1), Sotnikova E(#)(1), Skirko O(1), Divashuk 
M(1)(2), Kurilova O(1), Ershova A(1), Khlebus E(1), Zharikova A(1)(3)(4), 
Efimova I(1), Pokrovskaya M(1), Slominsky PA(5), Shalnova S(1), Meshkov A(#)(1), 
Drapkina O(#)(1).

Author information:
(1)Federal State Institution «National Medical Research Center for Therapy and 
Preventive Medicine» of the Ministry of Healthcare of the Russian Federation, 
Moscow, 101000, Russia.
(2)Kurchatov Genomics Center-ARRIAB, All-Russia Research Institute of 
Agricultural Biotechnology, Moscow 127550, Russia.
(3)Faculty of Bioengineering and Bioinformatics, Lomonosov Moscow State 
University, Moscow 119991, Russia.
(4)Institute for Information Transmission Problems, Russian Academy of Sciences, 
Moscow 127051, Russia.
(5)Institute of Molecular Genetics, Russian Academy of Sciences, Moscow 123182, 
Russia.
(#)Contributed equally

PURPOSE: Cystic fibrosis (CF) is one of the most common monogenic diseases with 
an autosomal recessive inheritance. Carrier screening leads to a reduction in 
the number of children born with CF disease. The aim of this study was to 
develop the custom panel for the diagnosis of heterozygous carriage of 
polymorphic variants in the CFTR gene and to establish their allelic frequencies 
(AF) in one of the Russian regions where ethnic Russians predominate.
PATIENTS AND METHODS: The diagnostic panel was designed on the basis of data 
from the register of CF patients in Russia for 2017 and validated on 22 blood 
samples of patients with previously genetically established CF. The study 
participants (n=642) for CF variants estimation were randomly selected from the 
population-based cohort study ESSE-Vologda. Genotypes were determined by 
real-time PCR on the QuantStudio 12K Flex Real-Time PCR System. Data processing 
was performed using the TaqMan Genotyper Software.
RESULTS: The proposed diagnostic panel allowed simultaneous analysis of 60 
variants of the CFTR gene. A total of 23 carriers of the following variants were 
identified among 642 participants: F508del (rs113993960) with a frequency of 
2.02%, L138ins (rs397508686) and 394delTT (rs121908769) - 0.47%, CFTRdele2.3 
(c.54-5940_273+10250del21080; p.S18Rfs*16) - 0.31%, R117H (rs78655421), and 
G542X (rs113993959) - 0.16%. The frequency of heterozygotes in the Russian 
population was 3.58% or 1:28 (CI95%: 2.28-5.33% by Clopper-Pearson exact 
method).
CONCLUSION: High frequency of heterozygous CFTR variants carriers and 
availability of highly productive diagnostic panel for detection of CFTR 
variants suggest the prospect of carrier screening for some common CF variants 
among Russian population.

© 2020 Kiseleva et al.

DOI: 10.2147/PGPM.S278806
PMCID: PMC7894124
PMID: 33623413

Conflict of interest statement: The authors declare that they have no competing 
interests.