pp. 77-80 in Intractable Neurological Disorders, Human Genome Research and Society. Proceedings of the Third International Bioethics Seminar in Fukui, 19-21 November, 1993.

Editors: Norio Fujiki, M.D. & Darryl R.J. Macer, Ph.D.


Copyright 1994, Eubios Ethics Institute All commercial rights reserved. This publication may be reproduced for limited educational or academic use, however please enquire with Eubios Ethics Institute.

Mortality rates for Huntington's disease in Japan, 1969-1992: geographical variations

Yoko Imaizumi
Director, Institute of Population Problems, Ministry of Health and Welfare, Tokyo 100, Japan


Introduction

The death rates for Huntington's disease (HD) in Japan were analyzed using the mortality statistics for 1969-1992. The overall death rate per million population was 0.15 for both sexes. Overall mean age at death was 49 years for males and 50 years for females. The geographical variations in the HD death rate were observed with the highest death rate in Yamagata prefecture (0.56), followed by Shiga (0.38), and Tokushima prefectures (0.37). On the other hand, the lowest rate was observed in Ibaraki and Kagoshima (0), Nagasaki and Aomori prefectures (0.03).

HD is an autosomal dominant character. The HD gene was assigned to chromosome 4 (1), and the gene cloned in 1993 (2). Almost all HD patients are heterozygote. Half of their children will have the HD gene, but they will not know until the onset of the disease. Recently predictive testing for HD has been developed, raising many ethical issues (3). In most Western countries the prevalence rates of HD are between 30 and 70 per million population (4). The lowest prevalence rate has been found in South African blacks (0.6, ref. 5), Japan (1.1-3.8: ref.6, 7), and Finland (5: ref. 8). Within Japan, the prevalence rate of HD is three times higher in Aichi (7) than in Ibaraki prefecture (6). Therefore it is of interest to know geographical variations in the HD death rate in Japan. Imaizumi (9) studied the geographical variations in the HD death rate in Japan during the period 1979-1985. After this we obtained much more geographical data on deaths due to HD. The present study deals with the geographical variations in the HD death rate during the period 1969-1992 except for 1975-1978. The aim of this paper is to provide basic data on genetic counseling for HD patients and useful data for planning health care facilities and research centres.

Materials and Methods

Data consisting of 359 HD deaths reported for 1969-1992 inclusive have been obtained from the death certificate records kept at the Ministry of Health and Welfare, Japan. The International Classification of Diseases in 1968 assigned a code 331.0 for HD in the eight edition and a code 333.4 in the ninth edition in 1979. The certificate includes information on sex, place of residence, dates of birth and death, and cause of death. Data on the general population were taken from the annual volumes of the "Vital Statistics of Japan for the Years 1969-1992" (10), which cover the entire population of Japan.

In computing the HD death rates, the number of deaths from HD in each sex were divided by the population size of each sex during the same period. For computing the regional HD death rates, the population size as the denominator in each prefecture was averaged every five census years from 1970 to 1990.

Results

Trends in the HD mortality rate: Table 1 shows trends in the HD death rates for each sex during the period 1969-1992. The linear regression coefficients of the HD death rate on the year (per 100,000 years) were -0.00005 (±0.00016) for males, and -0.00003 (±0.00016) for females. These values were not significant at the 5% level. The overall HD death rate was 0.15 per million population.

Mean age at death: Figure 1 shows the distribution of age at death in the HD by sex during the period 1969-1992. Age at death in HD ranged from 5-9 years to over 75 years. Among the 359 cases 4.7 percentage of HD patients died under 25 years old and 51.0 % under 50 years.

Figure 2 shows the secular changes in the mean age at death from HD in each sex during the period 1969-1992. The mean age at death in HD was 49 years for males and 47 years for females in 1969-1972 and the corresponding age in 1989-1992 was 50 and 54 years, respectively. Then mean age at death in HD was nearly constant for males and increased slightly for females during the period, and overall mean age±S.D. at death was 49.2±0.9 years for males and 50.0±1.7 years for females.

Geographical variation: Table 2 shows the HD death rate by prefecture during the period from 1969-1974 and 1979-1992. The overall HD death rate was 0.13 per million population. The highest death rate was seen in Yamagata prefecture (0.56), followed by Shiga (0.38), and Tokushima (0.37) prefectures. Therefore, the HD death rate in Yamagata prefecture was 4.3 times as high as the overall HD death rate in Japan. On the other hand, the lowest death rate (0) was seen in Ibaraki and Kagoshima prefectures. The second lowest HD death rate was seen in Nagasaki and Aomori prefectures (0.03).


Table 1: Death rate from Huntington's disease by sex during 1969-1992.

Columns across page: Year Number of deaths (Males; Females; Total); Death rate per million population (Males; Females; Total);

1969 3 7 10 0.060 0.135 0.098
1970 3 7 10 0.059 0.133 0.097
1971 10 6 16 0.195 0.113 0.153
1972 5 8 13 0.096 0.148 0.123
1973 4 13 17 0.075 0.236 0.157
1974 8 7 15 0.149 0.126 0.137
1975 9 9 18 0.164 0.159 0.162
1976 7 3 10 0.127 0.053 0.089
1977 11 6 17 0.197 0.104 0.150
1978 7 4 11 0.124 0.069 0.096
1979 9 9 18 0.158 0.154 0.156
1980 7 5 12 0.122 0.085 0.103
1981 10 6 16 0.173 0.101 0.137
1982 5 10 15 0.086 0.167 0.127
1983 13 14 27 0.222 0.232 0.227
1984 5 7 12 0.085 0.115 0.100
1985 12 14 26 0.203 0.229 0.216
1986 11 11 22 0.185 0.179 0.182
1987 6 5 11 0.101 0.081 0.091
1988 5 7 12 0.083 0.112 0.098
1990 8 9 17 0.133 0.144 0.139
1991 8 4 12 0.132 0.064 0.097
1992 0 11 11 0.000 0.175 0.089

Figure 1: Distribution of age at death from Huntington's disease by sex, during 1969-1974 and 1979-1992.

Figure 2: Trends of mean age at death from Huntington's disease by sex, during 1969-1992.

Table 2: Death rate of Huntington's disease per million population in each prefecture, 1969-1974 and 1979-1992.

Columns across page: Prefecture; Number of deaths (1969-1974; 1979-1985; 1986-1992; Total); Total Death rate;

Whole of Japan 81 126 96 303 0.131

Hokkaido 10 5 8 23 0.210
Aomori 1 0 0 1 0.034
Iwate 2 1 2 5 0.178
Miyagi 2 3 1 6 0.146
Akita 0 3 1 4 0.161
Yamagata 2 7 5 14 0.563
Fukushima 1 2 1 4 0.099
Ibaraki 0 0 0 0 0.000
Tochigi 0 2 1 3 0.085
Gunma 1 0 2 3 0.082
Saitama 0 2 3 5 0.047
Chiba 6 6 7 19 0.207
Tokyo 5 12 9 26 0.112
Kanagawa 2 6 2 10 0.073
Niigata 1 1 2 4 0.082
Toyama 0 1 1 2 0.092
Ishikawa 0 1 1 2 0.091
Fukui 0 0 1 1 0.063
Yamanashi 0 1 0 1 0.062
Nagano 2 3 0 5 0.121
Gifu 3 4 2 9 0.233
Shizuoka 1 3 0 4 0.059
Aichi 5 9 8 22 0.180
Mie 2 4 1 7 0.209
Shiga 3 1 4 8 0.376
Kyoto 2 4 0 6 0.122
Osaka 6 9 6 21 0.126
Hyogo 3 3 7 13 0.128
Nara 0 1 3 4 0.170
Wakayama 0 4 0 4 0.187
Tottori 1 0 0 1 0.084
Shimane 1 1 2 4 0.256
Okayama 5 1 2 8 0.217
Hiroshima 0 4 4 8 0.148
Yamaguchi 0 0 2 2 0.064
Tokushima 0 6 0 6 0.367
Kagawa 1 0 0 1 0.051
Ehime 1 3 1 5 0.168
Kochi 2 0 1 3 0.183
Fukuoka 5 8 3 16 0.179
Saga 0 2 0 2 0.116
Nagasaki 1 0 0 1 0.032
Kumamoto 3 0 1 4 0.113
Oita 0 2 1 3 0.124
Miyazaki 0 0 1 1 0.044
Kagoshima 0 0 0 0 0.000
Okinawa 1 0 0 1 0.069
Unknown 0 1 0 1 -


Discussion

According to Kurtzke (11), it was possible to obtain all deaths listed as HD anywhere on the certificates in Sweden (1969-1974) and Denmark (1961-1975). In these countries, the HD death rates were separately obtained as the "underlying cause of death", which constitutes of 68% of all deaths listed as HD, and remaining 32% as "contributory cause of death" or an "associated condition". However, these values are not obtainable in Japan. Routinely reported death data on the certificate records are based solely on deaths coded as underlying (primary) cause. Therefore the HD death rate (0.15 per million) in the present study is an underestimate.

The HD death rate reported in Japan is approximately one-tenth of the values from the Western Hemisphere (11) and United States whites (12). A similar tendency is also seen in the prevalence rates of HD (4, 7). As for geographical variations, the prevalence rate in HD was three times higher in Aichi (7) than in Ibaraki prefecture (6), whereas the corresponding HD death rates per million in the present study were 0.18 and 0, respectively. The HD death rate in Aichi Prefecture is equivalent to the average of the whole of Japan. It is suggested that the geographical variations in the HD death rate may represent those in the prevalence rate in Japan. Hogg et al. (13) computed regional HD death rates for the entire United States during the period l968-l974, where regional variation in the HD death rate was not marked. In the present study the HD death rate varied from zero in two prefectures to 0.56 per million in Yamagata Prefecture (Table 2). Hogg et al.(13) mentioned that regional mortality rates may reflect morbidity patterns and may be useful in planning health care facilities and research centers.


References

1. Gusella, J.F., et al. (1983) A polymorphic DNA marker genetically linked to Huntington's disease. Nature 306: 234-238.
2. Huntington's Disease Collaborative Research Group (1993) A novel gene containing a trinucleotide repeat that is expanded and unstable on Huntington's disease chromosomes. Cell 72: 971-83.
3. Holtzman, N. (1988) Recombinant DNA technology, genetic tests, and public policy. Amer. J. Human Genetics 42: 624.
4. McKusick, V. A., Mendelian Inheritance in Man: Catalogs of Autosomal Dominant, Autosomal Recessive, and X-linked Phenotypes (8th Ed.), (Baltimore: Johns Hopkins Univ. Press, 1988).
5. Hayden, M.R. & Beighton, P. (1977) Huntington's chorea in the Cape coloured community of South Africa. South Afr. Med. J. 52: 886-888.
6. Kanazawa, I. (1983) On prevalence rate of Huntington's disease in Ibaraki Prefecture, pp.151-156 in Annual Report of the Research Committee of CNS Degenerative Diseases, (The Ministry of Health and Welfare of Japan, Tokyo) (Summary in English).
7. Kishimoto, K., Nakamura, M. & Sotokawa, Y. (1957) Population genetics of Huntington's chorea in Japan. Annual Report of the Research Institute of Environmental Medicine, Nagoya University, 9: 195-211 (in Japanese).
8. Palo, J., Somer, H., Ikonen, E., Karila, L. and Peltonen, L. (1987) Low prevalence of Huntington's disease in Finland. Lancet I: 805-806.
9. Imaizumi, Y. (1989) Mortality rate of Huntington disease in Japan: Secular trends, marital status, and geographical variations. Jpn. J. Human Genet.34: 169-178.
10. Japan, Ministry of Health and Welfare (1971-1991): Vital Statistics, 1969-1992. Health and Welfare Statistics and Information Department, (Ministry of Health and Welfare, Tokyo) (Japanese).
11. Kurtzke, J.F. (l979) Huntington's disease: mortality and morbidity data from outside the United States. Adv. Neurol. 23: 13-25.
12. Kurtzke, J.F., Anderson, V.E., Beebe, G.W., Elston, R.C., Higgins, I., Hogg, J., Kurland, L., Muenter, M., Myrianthopoulos, N., Reed, T.E., Schoenberg, B., Schull, W.J., and Li, C.C. (1977) Report of the Work Group on Epidemiology, Biostatistics, and Population Genetics. In: Report: Commission for the Control of Huntington's Disease and Its Consequences. Vol. III, Part 1-Work Group Reports, Research. DHEW Pub. No.(NIH) 78-1503. pp.1-133 to 1-236. (US Government Printing Office, Washington, D.C, 1977).
13. Hogg, J.E., Massey, E.W. & Schoenberg, B.S. (l979) Mortality from Huntington's disease in the United States. Adv. Neurol. 23: 27-35.


To next chapter
To contents list
To book list
To Eubios Ethics Institute home page