Prevalence of 1-antitrypsin deficiency in Japan.

HUMAN GLUCOSE-6-PHOSPHATE DEHYDROGENASE VARIANTS 253 differentiating between G6PD variants not otherwise distinguishable. Determination of the precise amino acid substitutions of the G6PD variants could provide unambiguous evidence of their identity. Thus far, amino acid substitutions have been de- termined in only two G6PD variants (G6PD A+ and G6PD Hektoen), but technical improvements will facilitate such structural study of all variants in the future. Until that goal can be accomplished, the only recourse is a descriptive register. The accom- panying table includes all the published and unpub- lished variants known to the authors up to August 1970. We hope to prepare annual supplementary tables as further variants are described. In compiling the type and quantity of data included in the present tabulation, we have undoubtedly made errors both in interpretation and in transcription and we shall welcome having such errors called to our attention. ACKNOWLEDGEMENTS We are grateful to Dr P. McCurdy and Dr G. Sta- matoyannopoulos for making their results known to us before publication. REFERENCES WHO Scientific Group on the Standardization of Proce- dures for the Study of Glucose-6-Phosphate Dehydrog- enase (1967) Wld Hith Org. techn. Rep. Ser., No. 366 Prevalence of ai-Antitrypsin Deficiency in Japan * by KAzuo NoMIYAMA,1 HIROKO NoMIYAMA 2 & HISAO MATSUI 3 A high prevalence of pulmonary emphysema or chronic obstructive pulmonary disease has been found in people with a hereditary a1-antitrypsin deficiency (a1-ATD) (Eriksson 1965, Ganrot et al., 1967). Emphysema with a1-ATD is characterized by familial prevalence, a relatively early onset, exacerbation in winter, and panlobular emphysema without clinical chronic bronchitis (Eriksson 1964, Talamo et al, 1966). Irritation due, for example, to smoking, air pollution, or occupational exposure may lead to the onset of the clinical disease. A very high prevalence of the condition among a%-antitrypsin (a,-AT) deficient heterozygotes has been reported from Sweden and the USA (Table 1). The a1-ATD test has already been recommended in the USA for screening workers who might be exposed to irritant gases. Because apparently healthy people with a1-ATD may develop emphysema upon continuous exposure to low concentration of air pollutants, a screening survey for a,-ATD was carried out in the Shibukawa and Maebashi districts of Gunma Prefecture, Japan, in early 1970. * From the Department of Hygiene, Gunma University School of Medicine, Maebashi, Japan. 1 Associate Professor. 'Research Associate. Postgraduate Student. 2722B Methods Sera were collected at random from 433 residents over 40 years of age in the Shibukawa district and from 377 students 15-25 years of age and 150 pupils 14 years of age in the Maebashi district. Total antitrypsin activity was determined by a slight modification of the gelatin-film test (James et al., 1966). The gelatin film test for detecting al-ATD was a little less accurate than the photometric procedure (coefficient of variation in photometry 8.6%, compared with 22.5% for the gelatin-film test). The gelatin-film test, however, was found to be a simple and inexpensive procedure and was appro- priate for screening large populations. Results As seen in Table 1, no a1-ATD could be detected in 433 apparently normal individuals, and 1 and 2 presumed heterozygous individuals for al-ATD were found in other groups of 377 students and 150 pupils, respectively. The mean a,-AT levels were 1.90 mg+0.24 mg (mean ±standard deviation) and 1.79 mg +0.21 mg of trypsin inhibitor per millilitre of serum for the adults and the young people, respectively. The a,-AT level seemed to increase with age, although this increase was not significant (see Fig. 1). No Table 1. Prevalence of al -antitrypsin deficiency in normal populations No. of Heterozygotes Homozygotes C t Age-group determining Reference subjects (% (% Country (years) deerinigRaeec Results from earlier studies 193 2.1 0.0 USA (White) _ SP Kueppers et al., 1964 103 2.9 0.0 Sweden _ SP Eriksson, 1965 6 955 0.2 0.06 Sweden > 25 PEP + SP Eriksson, 1965 69 2.9 0.0 USA (Caucasian, _ SP, GF James et al., 1966 Negroid, Asian) 43 4.7 0.0 USA (7) - SP, RD Talamo et al., 1968 100 14.0 0.0 USA (7) 18-67 AACE Kueppers et al., 1969 88 9.1 0.0 USA (7) 70-97 AACE Kueppers et al., 1969 47 6.4 0.0 USA (?) - SP Lieberman, 1969 278 4.7 0.04 USA (?) (worker) SP Lieberman et al., 1969 Results from the present study 433 0.0 0.0 Japan > 40 GF 377 0.3 0.0 Japan 15-25 GF 150 1.3 0.0 Japan 14 GF a SP = spectrophotometry; GF = gelatin-film test; AACE = antigen-antibody crossed-electrophoresis; PEP = paper electrophoresis; RD = radial diffusion. notable difference in al-AT level could be observed between the sexes. Discussion The prevalence of a1-ATD in apparently normal Japanese people was found to be far lower than that 2.4 r E 2.2 cn .' 2.0 C h- < 1.8 ;R 1. 6 E a) -' 1.4 I ~~~~~~~~~~~~~~~~~~~~~~~~~I T II |~I I L l 10-19 20-29 30-39 40-49 50-59 60-69 70-79 80-89 Years of Age Fig. 1. al -Antitrypsin levels among different age- groups (solid line: males; dashed line: females; vertical lines: standard deviations). previously found in Swedish and American popula- tions (Table 1). The low prevalence of pulmonary emphysema in Japan may be related to the low prevalence of al-ATD. The prevalence of al-ATD in young people seemed to be higher than that in adults, as was found by Kueppers et al. (1969). The immunochemical procedure for estimating the a1-AT level is probably more accurate than the chemical procedure for total trypsin inhib- itor, because serum trypsin inhibitor is composed of al-AT (90 %), a2-macroglobulin, inter-a-tryp- sin inhibitor, a2-antitrypsin and a1-antichymotrypsin (Briscoe et al., 1966, Tarkoff et al., 1968). The level of al-AT, however, was reported to be as low as 60% of the normal level in heterozygotes and only 10% of the normal level in homozygotes, and it was reported that the levels in normal individuals, hete- rozygotes, and homozygotes did not overlap (Laurell & Eriksson, 1965). Accordingly, the determination of the level of the trypsin inhibitory capacity of serum may be useful for detecting al-ATD in spite of the possibility of obtaining some false positive or false negative values. In this connexion it is worth noting that Kueppers et al. (1969) found a normal a1-AT 254 NOTES I I I I PREVALENCE OF a1-ANTITRYPSIN DEFICIENCY IN JAPAN 255 level in 19 of 47 heterozygotes, suggesting that the a,-AT level may be raised to the normal range under certain physiological or pathological conditions such as infection and pregnancy. ACKNOWLEDGEMENTS The authors express their thanks to Professor S. Imamura and Dr Y. Shinozaki for allowing them to perform the survey, and to Dr E. C. Foulkes for correct- ing the manuscript. REFERENCES Briscoe, W. A., Kueppers, F., Davis, A. L. & Beam, A. G. (1966) Amer. Rev. resp. Dis., 94, 529 Eriksson, S. (1964) Acta med. scand., 175, 197 Eriksson, S. (1965) Acta med. scand., 177, Suppl., p. 432 Ganrot, P. O., Laurell, C.-B. & Eriksson, S. (1967) Scand. J. clin. Lab. Invest., 19, 205 James, K., Collins, M. L. & Fudenberg, H. H. (1966) J. Lab. clin. Med., 67, 528 Kueppers, F., Briscoe, W. A. & Beam, A. G. (1964) Science, 146, 1678 Kueppers, F., Fallat, R. & Larson, R. K. (1969) Science, 165, 899 Laurell, C.-B. & Eriksson. S. (1965) Clin. chim. Acta, 11, 395 Lieberman, J. (1969) New Engl. J. Med., 281, 279 Lieberman, J., Mittman, C. & Schneider, A. S. (1969) J. Amer. med. Ass., 210, 2055 Talamo, R. C., Blennerhassett, J. B. & Austen, K. F. (1966) New Engi. J. Med., 275, 1301 Talamo, R. C., Allen, J. D., Kahan, M. G. & Austen, K. F. (1968) New Engi. J. Med., 278, 345 Tarkoff, M. P., Kueppers, F., Miller, W. F. (1968) Amer. J. Med., 45, 220 Measurements of Concentrations of Human Serum Immunoglobulins * Concentrations of immunoglobulins in human se- rum are frequently measured for both clinical and research purposes, and the values have been ex- pressed in terms such as mg/ml. However, there has been little confidence that concentrations, as estimated by different laboratories using different reference materials, are comparable. With the object of improving the uniformity of estimates by diffe- rent laboratories, a freeze-dried preparation ofhuman serum, coded 67/86, has been assessed for use as a standard for measurements of human serum immu- noglobulins IgG, IgA, and IgM by techniques of immunodiffusion (Rowe, Anderson & Grab, 1970). Part of this batch of material has been established by the World Health Organization 1 as the Inter- national Reference Preparation of Human Immuno- globulins IgG, IgA, and IgM, and international units have been assigned to it such that each ampoule of the International Reference Preparation contains on average 100 IU of IgG, 100 IU of IgA, and 100 IU of IgM. The signatories of this note met recently to consider ways in which the International Reference Preparation might be used to promote uniformity of measurement. * This Note was drafted in February 1971 by the signa- tories listed on page 256. 1 WHO Expert Committee on Biological Standardization (1971) Wld Hlth Org. tecmn. Rep. Ser., No.1463. 2722c International collaborative studies have shown that reasonable agreement between estimates can be achieved in the measurement of IgG, IgA, and IgM in normal human serum using the International Refe- rence Preparation as a standard. (For example, the ratio of the highest and lowest values obtained by 11 different laboratories on one serum sample was 1.36 for IgG, 1.17 for IgA, and 1.31 for IgM). How- ever, estimates in terms of mg/ml of the immuno- globulin contents of a solution of the International Reference Preparation, obtained by comparison with purified immunoglobulins using gel-diffusion tech- niques, showed widely divergent values. The ratio of the highest and lowest values obtained by 9 or 10 different specialized laboratories was 2.2 for IgG, 3.2 for IgA, and 5.0 for IgM (Rowe, Anderson & Grab, 1971). Such divergence of results is consistent with the present lack of uniformity of the numerous immunoglobulin standards prepared in different laboratories, for which concentrations are usually expressed as mg/ml. There would be more agree- ment between laboratories if serum concentrations of IgG, IgA, and IgM were estimated by comparison with the International Reference Preparation, and expressed in terms of International Units per ml. It is therefore proposed: (1) That concentrations of IgG, IgA, and IgM in working standards, as distributed by manufac-