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April 1996, Volume 46, Issue 4


Genetic Markers

Anjum Shahid  ( PMRC Research Centre, Jinnah Postgraduate Medical Centre, Karachi. )

Role of genetic and environmental factors in predispo­sition of many common diseases has been widely recognized. The genetic component predisposes and an environmental component help in the manifestation of the disease. Genetic studies helps in detecting predisposed persons so that they may be advised against exposure to environmental risk factors1. An identification of individuals who may be predis­posed to such diseases could provide valuable information which may be of immense help not only in the management of the disease in the affected person but also in planning the future strategies for the family.
Duodenal ulcer is a common gastrointestinal problem believed to exist in families. Many pedigrees have been reported in which several members had an ulcer. The disease was found to oceurtwo to two and a half times more frequently among siblings of ulcer patients than among ulcer free subjects from a comparable population2. Duodenal ulcer was 2.6 times more frequent in sibs of patients than in others3.
Genetic factors have long been suspected because of an increased frequency of the disease among the first degree relatives of the patients4, greater concordance between monozygotic and dizygotic twins5 and the associationofABO blood groups with the disorder4. Secretor and non-secretor status4, ABO blood groups6, HLA typing7, serum pepsino­gen8 and serum alpha 1 antitrypsin9 serves as genetic markers of the ulcer diathesis. The magnitude of association between blood group 0 and non-secretor status with duodenal ulcer appears weak6, while raised serum pepsinogen and low alpha 1 antitrypsin have been found to identify those at an increased risk for the development of the disease10. Due to scarcity of data which could accurately indicate whether there exist any associationbetween the various genetic markers and duodenal ulcer, it appears appropriate to establish a possible co-relation between them, more so because duodenal ulcer is common in the local population and the etiology is yet to be determined either to be of genetic or non-genetic in origin.
In a recently concluded study, it was observed that only 28% of the patients had raised serum pepsinogen, while serum alpha 1 antitrypsin was low in 35% of the patients. Other findings include dominant blood group 0, lower mean age, an early onset of the disease, an increased frequency of gastroin­testinal bleeding and ulcer perforation thereby confirming the strong association of duodenal ulcer with all the markers. It appears that the genetic etiology of the disease existed in just 28% of the patients while the rest comprising a large majority (72%) had ulcer as a result of neuro endocrinological or environmental factors which are also known to cause the disease11.
A deficiency of pmtease inhibitor alpha 1 antitrypsin might be linked to causation or persistence of duodenal ulcer. This postulate is supported by the findings that patients identified with partial deficiency of protease inhibitor had relapse and duodenitis persisted inspite of lonpterm follow-up and treatment with H2 receptor antagonist12.
Duodenal ulcer patients manifesting hyperpepsino­genemia or low serum alpha 1 antitrypsin reqUire further investigation in the family to identify siblings and progeny carrying the trait and thus, at higher risk, so that they could be shielded fmm aggravating environmental and other factors:


1. Habibullah, CM. and Radha, V. The genetics of peptic ulcer disease. Trop. Gastroent., 1985; 6: 132.
2. Doll, R. and Buch, J. Hereditaty factors in peptic ulcer. Ann. Eugenics, 1960;19. 135.
3. Doll, R. and Ke.Lock, T.D. The separate inheritance of gastric and duodenal ulcer. Ann. Eugenics.. 1951 ;16:231.
4. McConnel. R.Gastric and duodenal ulcer, the genetics of the gastrointestinal disorders. London, Oxford Univ. Press, 1966, p. 76.
5. Gotlieb - Jensen, K. Peptic ulcer: genetic and epidemiological aspects based on twin studies. Copenhagen, Munksgaard, 1972.
6. Langman. M.J.S, Blood groups and alimentary disorders. Clin. Gastroent., 1973;2:497.
7. Ellis, A. and Woodrow, J.C. HLA and duodenal ulcer. Gut., 1979;9:760.
8. Habibullah, CM., Ali, MM., Ishaq, M. et al. Study of duodenal ulcer disease in 100 families using serum pepsinogen as a genetic marker. Gut., 1984:25:1380.
9. Kishore, N. Alpha I antitrypsin dcficiency in duodenal ulcer. Trop. Gastroent. 1980;1:193.
10. Mirsky, I.A. Physiologic, psychologic and social determinants in the etiology of duodenal ulcer. Amer. 3. Dig. Dis. 1958;3:285.
11. Shahid, A., Zuberi, S.J., Siddiqui, A.A. and Waqar MA. (Unpublished data).
12. Shahid, A., Siddiqui, A.A.. Zuberi, S.J. and Waqar, M.A. Serum Alpha I antitrypsin and duodenal ulcer. J. Gastroent. Hepatol., 1993;8:505.

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