PMID- 1427021
OWN - NLM
STAT- MEDLINE
DCOM- 19921209
LR  - 20151119
IS  - 0741-0395 (Print)
IS  - 0741-0395 (Linking)
VI  - 9
IP  - 5
DP  - 1992
TI  - Family study of alpha 1-antitrypsin deficiency: effects of cigarette smoking, 
      measured genotype, and their interaction on pulmonary function and biochemical 
      traits.
PG  - 317-31
AB  - To gain insight into the variable expression of lung disease in alpha 
      1-antitrypsin (alpha 1AT) deficiency, five quantitative variables including 
      forced expiratory volume at 1 sec (FEV1), forced expiratory flow rate between 25 
      and 75% of forced vital capacity (FEF25-75), total serum alpha 1AT, oxidized 
      serum alpha 1AT, and total serum immunoglobulin E (IgE) were measured in alpha 
      1AT deficient individuals and their families. The effect of a known, measured 
      genotype (the Pi type) was estimated for each quantitative trait; the influence 
      of mode of case ascertainment on the measured genotype effect was also assessed. 
      These analyses showed that total alpha 1AT levels are strongly influenced by Pi 
      type; IgE levels are unaffected by Pi type; and FEV1, FEF25-75, and oxidized 
      alpha 1AT are moderately influenced by Pi type. The effect of 
      genotype-by-environment interaction between Pi type and pack-years of cigarette 
      smoking on the five quantitative phenotypes was studied using an analysis of 
      covariance. Significant Pi x pack-years interaction was evident for FEV1, but 
      this effect is confounded in this data set with the Pi x age interaction. 
      Probands who were ascertained because they had chronic obstructive pulmonary 
      disease (COPD) do not demonstrate the significant Pi x pack-years interaction 
      effect of the Pi x pack-years subjects ascertained for other reasons demonstrate. 
      The effect of the Pi x pack-years interaction on FEV1 was no longer significant 
      on a transformed scale, (FEVf12,) thus providing an additive scale for future 
      data analysis. The increased sensitivity of Pi MZ individuals in our sample to 
      cigarette smoking reduced the Pi x packs-years interaction effect on FEF25-75 to 
      borderline significance. This investigation has provided an opportunity to 
      incorporate both measured genotype and genotype-by-environment interaction 
      analyses into the study of the variable expression of lung disease in Pi Z 
      individuals.
FAU - Silverman, E K
AU  - Silverman EK
AD  - Division of Biostatistics, Washington University School of Medicine, St. Louis 
      63110.
FAU - Province, M A
AU  - Province MA
FAU - Campbell, E J
AU  - Campbell EJ
FAU - Pierce, J A
AU  - Pierce JA
FAU - Rao, D C
AU  - Rao DC
LA  - eng
GR  - 5T32/PHS HHS/United States
GR  - GM 28719/GM/NIGMS NIH HHS/United States
GR  - GM 7200/GM/NIGMS NIH HHS/United States
GR  - etc.
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Genet Epidemiol
JT  - Genetic epidemiology
JID - 8411723
RN  - 0 (alpha 1-Antitrypsin)
RN  - 37341-29-0 (Immunoglobulin E)
SB  - IM
MH  - Family
MH  - Female
MH  - Fluorescent Antibody Technique
MH  - Genotype
MH  - Humans
MH  - Immunoglobulin E/blood
MH  - Lung Diseases, Obstructive/enzymology/genetics
MH  - Male
MH  - Phenotype
MH  - Pulmonary Emphysema/enzymology/genetics
MH  - *Respiratory Mechanics
MH  - Risk Factors
MH  - *Smoking
MH  - Surveys and Questionnaires
MH  - alpha 1-Antitrypsin/*genetics/metabolism
MH  - *alpha 1-Antitrypsin Deficiency
EDAT- 1992/01/01 00:00
MHDA- 1992/01/01 00:01
CRDT- 1992/01/01 00:00
PHST- 1992/01/01 00:00 [pubmed]
PHST- 1992/01/01 00:01 [medline]
PHST- 1992/01/01 00:00 [entrez]
AID - 10.1002/gepi.1370090504 [doi]
PST - ppublish
SO  - Genet Epidemiol. 1992;9(5):317-31. doi: 10.1002/gepi.1370090504.