116 This PDF is available for free download from a site hosted by Medknow Publications (www.medknow.com). Original Article Genetic heterogeneity in duodenal ulceration A. Venkateshwari, A. Vidyasagar*, N. Pratibha Department of Genetics, Osmania University, Hyderabad - 500 007, and *Gastroenterology Unit, Gandhi Hospital, Secunderabad - 500 003, India features but variations in the mode of inheritance in BACKGROUND: Duodenal ulcer (DU) is a multifactorial disorder with different etiological and pathogenetic different families. It can be resolved based on age at mechanisms. Evidence for the role of genetic factors such onset of the condition, mode of inheritance and variation as familial aggregation, twin studies, ABO blood groups, ABH nonsecretor status and hyperpepsinogenemia have of associated genetic markers. [1] Duodenal ulcer (DU) been reported in DU. Genetic heterogeneity of cases with is a multifactorial disorder associated with different familial incidence will provide information regarding the etiological and pathogenetic mechanisms. [2] Evidence association of qualitative and quantitative traits. AIM: Hence, the present study is envisaged at identifying for the involvement of genetic factors in duodenal ulcer the segregant and deviant groups based on parental includes a) familial aggregation b) twin studies c) phenotypes and their association with other quantitative association of genetic factors such as ABO blood groups, MATERIALS AND METHODS: 62 out of 462 endoscopically ABH non secretor status, hyperpepsinogenemia, HLA confirmed duodenal ulcer cases were considered for the antigens etc. [3-6] Hence, heterogeneity in duodenal ulcers analysis of genetic heterogeneity. This was resolved through the calculation of genetic risk estimates of sporadic cases in (DU) was sought to be resolved through the genetic risk multiplex families based on different modes of inheritance estimates of sporadic cases in multiplex families based and variation in associated genetic and biochemical markers. RESULTS: Mean age at onset in simplex and multiplex on different modes of inheritance and variation in cases was found to vary indicating the presence of genetic associated genetic and biochemical factors. heterogeneity in the expression of the disease. Segregant and deviant groups were identified based on mortons probability risk estimates and examined for the possible Materials and Methods association of qualitative and quantitative markers such as pepsinogen phenotype, serum and tissue pepsinogen levels, cathepsin E, malondialdehyde and ceruloplasmin 462 confirmed duodenal ulcer cases in the age group of 18-74 years, referred to the Gastroenterology unit of Conclusions: The study thus highlighted the presence of genetic heterogeneity in the expression of the disease. The the Gandhi Hospital, Secunderabad for a period of four markers. levels. risk factors associated with segregant type were normal serum and tissue pepsinogen levels increased malondialdehyde levels and association of AC phenotype while the deviant group was characterized by early age at onset with hyper pepsinogenemia and reduced cathepin E levels. Key words: Age at onset, cathepsin E, deviant families, duodenal ulcer, genetic heterogeneity, pepsinogen, segregant Introduction Genetic heterogeneity refers to the existence of two or more genetically distinct entities with similar clinical years were considered for the present study. Provisional diagnosis of ulcers was based on clinical symptoms e.g., history of vomiting, belching, bloating, upper abdominal pain etc. Endoscopically confirmed duodenal ulcer cases were considered for the present study. Cases with unclear etiology or cases with associated conditions were not considered for the present study. Information on clinical symptoms, age, duration of the condition, sex, nutritional factors, addictions to smoking, alcohol, consanguinity and familial incidence were obtained from all individuals as per the standard proforma. Blood and mucosal tissue samples was collected from all the patients for the analysis of parameters viz; serum and tissue pepsinogen, [7] cathepsin E, [8] malondialdehyde, [9] Address for Correspondence: Pratibha Nallari, Department of Genetics, Osmania University, Hyderabad - 500 007, India. E-mail: prathinallari@yahoo.com Indian Journal of Human Genetics September-December 2006 Volume 12 Issue 3