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ALDEHYDE DEHYDROGENASE-2 DEFICIENCY AND ARTICULAR COLLAGEN
984
15qll-ql3 abnormality. However, if the submicroscopic hypothesis is valid hyperlexia in someone with Prader-Willi syndrome is an interesting finding because the chromosomal abnormality for this syndrome is a neighbour of that for some cases of dyslexia: this suggests the possibility of an enzyme or peptide which may modulate the symptomatically opposite conditions of dyslexia and hyperlexia. Family and chromosomal studies of hyperlexic patients, using the techniques of molecular genetics, may address this issue more definitively. Medical Centre Rehabilitation Hospital, Grand Forks, North Dakota 58202, USA
LARRY BURD
School of Medicine, University of North Dakota
JACOB KERBESHIAN
1. Smith
SD, Kimberling WJ, Pennington BF, Lubs HA. Specific reading disability: an inherited form through linkage analysis. Science 1983; 219:
The inherent aversion to alcohol3 may be a protective process since vascular necrosis of the head of the femur is associated with alcoholism.8 In fact four of our cases had a history of alcohol abuse. Whether this fmdmg has relevance to the aetiology of osteoarthritis remains to be elucidated but it does raise the possibility that modification of collagen cross-linking may protect against erosion or that alcohol abuse is a more frequent cause of erosion of articular collagen than currently assumed. We thank the Hong Kong Polytechnic Research Sub-committee and the Wideland Foundation for financial support. Department of Health Sciences, Hong Kong Polytechnic, Hung Hom, Kowloon, Hong Kong, and Queen Elizabeth Hospital, Kowloon, Hong Kong
W. H. P. LEWIS YORK CHOW
KITTY K. Y. SUN
identification of
1345-47. 2. Smith SD, Pennington
heterogeneity
in
BF, Kimberling WJ, Fain PR, Ing PS, Lubs HA. Genetic specific reading disability. Am J Hum Genet 1986, 39 (suppl);
abstr: 169. 3.
Bisgaard ML, Eiberg H, Moller N, Niebuhn E, Mohr J. Dyslexia and chromosome 15 heteromorphism. Negative lod scores in a Danish material. Clin Genet 1987; 32:
118-19 4. Neredleman RM. A
linguistic analysis of hyperlexia. In: Johnson EJ, Thewd CJ, eds. Proceedings of the Second International Congress for the Study of Child Language. Washington DC University Press of America, 1982: 473-82. 5. Ledbener DH, Greenberg F, Holm VA, Cassidy SB. Conference report Second Annual Prader-Willi Syndrome Scientific Conference Am J Med Genet 1987; 28: 779-90
ALDEHYDE DEHYDROGENASE-2 DEFICIENCY AND ARTICULAR COLLAGEN
SiR,—Aldehyde dehydrogenase (ALDH) occurs in man in four torms.1 ALDH-2 occurs mainly in liver, kidney, and connective tissues. A common polymorphism of this enzyme occurs in Asian populations as a deficiency characterised by the production of an inactive protein that is immunologically crossreactive with the active enzyme.2 The only obvious physiological effect is alcohol intolerance.3 We report a possible further advantageous effect. The subjects were all ethnic Chinese and consisted of a mixed group of orthopaedic patients who had undergone surgical procedures requiring a linear incision and a control group of staff and students of the polytechnic. ALDH-2 phenotypes were measured by a modification of the method of Goedde et al.4 ALDH-21 is the active enzyme, and ALDH-2is the inactive enzyme. There was a significant difference in the frequencies of the two
phenotypes:
prompted us to question whether the difference was due to a subgroup within the patients. If the patients who had undergone a total joint replacement (12 hip,I knee) were excluded, the difference between the two groups was no longer significant. In view of the small number of cases, we felt that this approach was more valid than a comparison of the joint replacement group with controls. It is likely that aldehydes formed as a result of normal metabolism
I, Povey S, West LF, Parrington JM, Hopkinson DA. Chromosome assignment, biochemical and immunological studies on a human aldehyde dehydrogenase, ALDH3. Ann Hum Genet 1985; 49: 87-100. 2. Yoshida A, Huang IY, Ikawa M. Molecular abnormality of an inactive aldehyde dehydrogenase variant commonly found in orientals Proc Natl Acad Sci USA 1984; 81: 258-61. 3. Harada S, Agarwal DP, Goedde HW, Ishikawa B. Aldehyde dehydrogenase isoenzyme variation and alcoholism in Japan. Pharmacol Biochem Behav 1983; 18 1. Santisteban
(suppl 1): 151-53. 4. Goedde W, Agarwal DP, Harada S. Genetic studies on alcohol metabolizing enzymes detection of isoenzymes in hair roots Enzyme 1980; 25: 281-86. 5. Goedde HW, Agarwal DP, Harada S. Pharmacogenetics of alcohol sensitivity Pharmacol Biochem Behav 1983, 18 (suppl 1): 161-66 6. Haliwell B, Gutteridge JMC Free radicals in biology and medicine Oxford: Oxford University Press, 1985 7. Eyre DR, Paz MA, Gallop PM. Cross linking in collagen and elastin. Annu Rev Biochem 1984; 53: 717-48. 8. Patterson RJ, Bickel WH, Dahlin DC. Idiopathic avascular necrosis of the head of the femur, a study of 52 cases. J Bone Joint Surg Am 1984; 48: 267-82
WEIGHT IN INFANCY AND DEATH FROM ISCHAEMIC HEART DISEASE
SiR,—Professor Barker and colleagues (Sept 9, p 577) report that among the men who died mean birthweight was not related to social class at death. Since the information on social class came exclusively from death certificates, current social status could not be established for the 4468 survivors in the study. Consequently, Barker et al were unable to examine the relation between birthweight and adult social class for all members of the cohort born between 1911 and 1930. However, readily available statistics can throw some light on this relation. In 1986, 6-3% of all legitimate babies in England and Wales weighed less than 2500 g (defmed as low birthweight); the percentage of low-weight births in social class 1,11, and IIINM was below the national average, whereas that seen in classes III M, IV, and V was above average:1
This
will be cleared from the tissues of ALDH-2 deficient individuals only by diffusion into the vascular system. In a tissue such as articular collagen this would presumably take longer than in more vascular tissue. Aldehydes occur in several metabolic pathways, including the detoxification of ethanol. Little is known about the effect of free aldehydes at very low concentrations. ALDH-2 oxidises a wide range of aldehydes although it is most active against short-chain monoaldehydes. Thus the absence of this enzyme may result in higher levels of a number of aldehydes. Cross-linking in collagen involves aldehyde groups and the articular collagen of ALDH-2 deficient individuals may be more highly cross-linked than that of non-deficient individuals. Also, in the absence of the dehydrogenase pathway, aldehydes may be metabolised via the oxidative pathway (aldehyde oxidase and xanthine oxidase), which generates hydrogen peroxide and superoxide radicalswhich may catalyse a more exotic and more stable matrix.7
Data for legitimate births only, classified by father’s occupation. The Office of Population Censuses and Surveys (OPCS) only started routine collection of all birthweight data in 1975. Thus, it is impossible to examine directly whether there was a social class gradient in birthweight between 1911 and 1930. However, a pronounced social-class gradient in infant mortality has been recorded in England and Wales since the early years of this century.2 Children born to class IV and V parents are more likely to die in their first year of lite than those born into social classes I and II. Infant death is associated with low birthweight.1 Consequently, the social-class gradient in infant mortality during the three decades when Barker and colleagues’ cohort was born almost certainly reflected, in part, a corresponding social-class gradient in birthweight. In other words, low birthweight babies in the cohort were more likely to have been born into social class IV and V families than were the heavier babies. This notion is relevant since, in Great Britain, there has been little inter-generational class mobility among men bom in the first half of the twentieth century. Low-birthweight babies bom into unfavourable socioeconomic circumstances will, on the whole, have retained their poor social ranking during adult life. Therefore, in the
15qll-ql3 abnormality. However, if the submicroscopic hypothesis is valid hyperlexia in someone with Prader-Willi syndrome is an interesting finding because the chromosomal abnormality for this syndrome is a neighbour of that for some cases of dyslexia: this suggests the possibility of an enzyme or peptide which may modulate the symptomatically opposite conditions of dyslexia and hyperlexia. Family and chromosomal studies of hyperlexic patients, using the techniques of molecular genetics, may address this issue more definitively. Medical Centre Rehabilitation Hospital, Grand Forks, North Dakota 58202, USA
LARRY BURD
School of Medicine, University of North Dakota
JACOB KERBESHIAN
1. Smith
SD, Kimberling WJ, Pennington BF, Lubs HA. Specific reading disability: an inherited form through linkage analysis. Science 1983; 219:
The inherent aversion to alcohol3 may be a protective process since vascular necrosis of the head of the femur is associated with alcoholism.8 In fact four of our cases had a history of alcohol abuse. Whether this fmdmg has relevance to the aetiology of osteoarthritis remains to be elucidated but it does raise the possibility that modification of collagen cross-linking may protect against erosion or that alcohol abuse is a more frequent cause of erosion of articular collagen than currently assumed. We thank the Hong Kong Polytechnic Research Sub-committee and the Wideland Foundation for financial support. Department of Health Sciences, Hong Kong Polytechnic, Hung Hom, Kowloon, Hong Kong, and Queen Elizabeth Hospital, Kowloon, Hong Kong
W. H. P. LEWIS YORK CHOW
KITTY K. Y. SUN
identification of
1345-47. 2. Smith SD, Pennington
heterogeneity
in
BF, Kimberling WJ, Fain PR, Ing PS, Lubs HA. Genetic specific reading disability. Am J Hum Genet 1986, 39 (suppl);
abstr: 169. 3.
Bisgaard ML, Eiberg H, Moller N, Niebuhn E, Mohr J. Dyslexia and chromosome 15 heteromorphism. Negative lod scores in a Danish material. Clin Genet 1987; 32:
118-19 4. Neredleman RM. A
linguistic analysis of hyperlexia. In: Johnson EJ, Thewd CJ, eds. Proceedings of the Second International Congress for the Study of Child Language. Washington DC University Press of America, 1982: 473-82. 5. Ledbener DH, Greenberg F, Holm VA, Cassidy SB. Conference report Second Annual Prader-Willi Syndrome Scientific Conference Am J Med Genet 1987; 28: 779-90
ALDEHYDE DEHYDROGENASE-2 DEFICIENCY AND ARTICULAR COLLAGEN
SiR,—Aldehyde dehydrogenase (ALDH) occurs in man in four torms.1 ALDH-2 occurs mainly in liver, kidney, and connective tissues. A common polymorphism of this enzyme occurs in Asian populations as a deficiency characterised by the production of an inactive protein that is immunologically crossreactive with the active enzyme.2 The only obvious physiological effect is alcohol intolerance.3 We report a possible further advantageous effect. The subjects were all ethnic Chinese and consisted of a mixed group of orthopaedic patients who had undergone surgical procedures requiring a linear incision and a control group of staff and students of the polytechnic. ALDH-2 phenotypes were measured by a modification of the method of Goedde et al.4 ALDH-21 is the active enzyme, and ALDH-2is the inactive enzyme. There was a significant difference in the frequencies of the two
phenotypes:
prompted us to question whether the difference was due to a subgroup within the patients. If the patients who had undergone a total joint replacement (12 hip,I knee) were excluded, the difference between the two groups was no longer significant. In view of the small number of cases, we felt that this approach was more valid than a comparison of the joint replacement group with controls. It is likely that aldehydes formed as a result of normal metabolism
I, Povey S, West LF, Parrington JM, Hopkinson DA. Chromosome assignment, biochemical and immunological studies on a human aldehyde dehydrogenase, ALDH3. Ann Hum Genet 1985; 49: 87-100. 2. Yoshida A, Huang IY, Ikawa M. Molecular abnormality of an inactive aldehyde dehydrogenase variant commonly found in orientals Proc Natl Acad Sci USA 1984; 81: 258-61. 3. Harada S, Agarwal DP, Goedde HW, Ishikawa B. Aldehyde dehydrogenase isoenzyme variation and alcoholism in Japan. Pharmacol Biochem Behav 1983; 18 1. Santisteban
(suppl 1): 151-53. 4. Goedde W, Agarwal DP, Harada S. Genetic studies on alcohol metabolizing enzymes detection of isoenzymes in hair roots Enzyme 1980; 25: 281-86. 5. Goedde HW, Agarwal DP, Harada S. Pharmacogenetics of alcohol sensitivity Pharmacol Biochem Behav 1983, 18 (suppl 1): 161-66 6. Haliwell B, Gutteridge JMC Free radicals in biology and medicine Oxford: Oxford University Press, 1985 7. Eyre DR, Paz MA, Gallop PM. Cross linking in collagen and elastin. Annu Rev Biochem 1984; 53: 717-48. 8. Patterson RJ, Bickel WH, Dahlin DC. Idiopathic avascular necrosis of the head of the femur, a study of 52 cases. J Bone Joint Surg Am 1984; 48: 267-82
WEIGHT IN INFANCY AND DEATH FROM ISCHAEMIC HEART DISEASE
SiR,—Professor Barker and colleagues (Sept 9, p 577) report that among the men who died mean birthweight was not related to social class at death. Since the information on social class came exclusively from death certificates, current social status could not be established for the 4468 survivors in the study. Consequently, Barker et al were unable to examine the relation between birthweight and adult social class for all members of the cohort born between 1911 and 1930. However, readily available statistics can throw some light on this relation. In 1986, 6-3% of all legitimate babies in England and Wales weighed less than 2500 g (defmed as low birthweight); the percentage of low-weight births in social class 1,11, and IIINM was below the national average, whereas that seen in classes III M, IV, and V was above average:1
This
will be cleared from the tissues of ALDH-2 deficient individuals only by diffusion into the vascular system. In a tissue such as articular collagen this would presumably take longer than in more vascular tissue. Aldehydes occur in several metabolic pathways, including the detoxification of ethanol. Little is known about the effect of free aldehydes at very low concentrations. ALDH-2 oxidises a wide range of aldehydes although it is most active against short-chain monoaldehydes. Thus the absence of this enzyme may result in higher levels of a number of aldehydes. Cross-linking in collagen involves aldehyde groups and the articular collagen of ALDH-2 deficient individuals may be more highly cross-linked than that of non-deficient individuals. Also, in the absence of the dehydrogenase pathway, aldehydes may be metabolised via the oxidative pathway (aldehyde oxidase and xanthine oxidase), which generates hydrogen peroxide and superoxide radicalswhich may catalyse a more exotic and more stable matrix.7
Data for legitimate births only, classified by father’s occupation. The Office of Population Censuses and Surveys (OPCS) only started routine collection of all birthweight data in 1975. Thus, it is impossible to examine directly whether there was a social class gradient in birthweight between 1911 and 1930. However, a pronounced social-class gradient in infant mortality has been recorded in England and Wales since the early years of this century.2 Children born to class IV and V parents are more likely to die in their first year of lite than those born into social classes I and II. Infant death is associated with low birthweight.1 Consequently, the social-class gradient in infant mortality during the three decades when Barker and colleagues’ cohort was born almost certainly reflected, in part, a corresponding social-class gradient in birthweight. In other words, low birthweight babies in the cohort were more likely to have been born into social class IV and V families than were the heavier babies. This notion is relevant since, in Great Britain, there has been little inter-generational class mobility among men bom in the first half of the twentieth century. Low-birthweight babies bom into unfavourable socioeconomic circumstances will, on the whole, have retained their poor social ranking during adult life. Therefore, in the