Two novel mutations in surfactant protein-C, lung function and obstructive lung disease

TY - JOUR

T1 - Two novel mutations in surfactant protein-C, lung function and obstructive lung disease

AU - Baekvad-Hansen, Marie

AU - Nordestgaard, Børge G

AU - Tybjaerg-Hansen, Anne

AU - Dahl, Morten

N1 - Copyright 2009 Elsevier Ltd. All rights reserved.

PY - 2010/3/1

Y1 - 2010/3/1

N2 - Dominant mutations in the surfactant protein-C(SFTPC) gene have been linked with interstitial lung disease. The frequency of lung disease due to SFTPC mutations in the general population is unknown. The aim of this study was to identify novel SFTPC mutations that are associated with lung function or disease in the general population. We resequenced the SFTPC gene in 760 individuals and identified 18 genetic variants, of which 5 were novel. Of the five novel mutations, two were situated in highly conserved areas of the SFTPC gene: A53T and Y106X. We genotyped the Copenhagen City Heart Study(n=10,604) and the Copenhagen General Population Study(n=37,337) to assess the clinical relevance of these mutations. Genotyping identified 36 individuals heterozygous for A53T and 3 individuals heterozygous for Y106X. A53T heterozygotes and Y106X heterozygotes did not differ from non-carriers in FEV(1)% predicted, FVC% predicted or FEV(1)/FVC. A53T heterozygotes had a two-fold increased risk for asthma in the Copenhagen City Heart Study and Copenhagen General Population Study combined (adjusted odds ratio 2.2(1.0-4.9)). A53T heterozygotes did not differ consistently from non-carriers in risk of chronic obstructive pulmonary disease or interstitial lung disease. No Y106X heterozygotes suffered from asthma, chronic obstructive pulmonary disease (COPD), or interstitial lung disease. We identified two novel mutations in highly conserved areas of the SFTPC gene, and show that heterozygotes for the mutations have normal lung function and are unaffected by COPD and interstitial lung disease. A53T heterozygotes had increased asthma risk, but further research is required to conclusively determine whether this mutation is associated with asthma.

AB - Dominant mutations in the surfactant protein-C(SFTPC) gene have been linked with interstitial lung disease. The frequency of lung disease due to SFTPC mutations in the general population is unknown. The aim of this study was to identify novel SFTPC mutations that are associated with lung function or disease in the general population. We resequenced the SFTPC gene in 760 individuals and identified 18 genetic variants, of which 5 were novel. Of the five novel mutations, two were situated in highly conserved areas of the SFTPC gene: A53T and Y106X. We genotyped the Copenhagen City Heart Study(n=10,604) and the Copenhagen General Population Study(n=37,337) to assess the clinical relevance of these mutations. Genotyping identified 36 individuals heterozygous for A53T and 3 individuals heterozygous for Y106X. A53T heterozygotes and Y106X heterozygotes did not differ from non-carriers in FEV(1)% predicted, FVC% predicted or FEV(1)/FVC. A53T heterozygotes had a two-fold increased risk for asthma in the Copenhagen City Heart Study and Copenhagen General Population Study combined (adjusted odds ratio 2.2(1.0-4.9)). A53T heterozygotes did not differ consistently from non-carriers in risk of chronic obstructive pulmonary disease or interstitial lung disease. No Y106X heterozygotes suffered from asthma, chronic obstructive pulmonary disease (COPD), or interstitial lung disease. We identified two novel mutations in highly conserved areas of the SFTPC gene, and show that heterozygotes for the mutations have normal lung function and are unaffected by COPD and interstitial lung disease. A53T heterozygotes had increased asthma risk, but further research is required to conclusively determine whether this mutation is associated with asthma.

KW - Adult

KW - Aged

KW - Female

KW - Gene Frequency

KW - Genetic Predisposition to Disease

KW - Genotype

KW - Heterozygote

KW - Humans

KW - Lung Diseases, Obstructive

KW - Male

KW - Middle Aged

KW - Mutation

KW - Odds Ratio

KW - Phenotype

KW - Pulmonary Surfactant-Associated Protein C

KW - Respiratory Function Tests

U2 - 10.1016/j.rmed.2009.10.012

DO - 10.1016/j.rmed.2009.10.012

M3 - Journal article

C2 - 19910179

SN - 0954-6111

VL - 104

SP - 418

EP - 425

JO - Respiratory Medicine

JF - Respiratory Medicine

IS - 3

ER -