Journal of Pediatric Gastroenterology & Nutrition:
Original Articles: Gastroenterology
Consanguinity and Inflammatory Bowel Diseases: Is There a Relation?
Mouzan, Mohammad El*; Al-Mofarreh, Mohammad†; Assiri, Asaad*; Hamid, Yassin*; Saeed, Anjum*
*Department of Pediatrics, Division of Gastroenterology, College of Medicine and King Khaled University Hospital, King Saud University
†Al-Mofarreh Poly Clinic, Division of Gastroenterology, Riyadh, Saudi Arabia.
Address correspondence and reprint requests to Mohammad I. El Mouzan, MD, Professor of Pediatrics, Division of Gastroenterology, King Saud University, P. O. Box 2925, Riyadh 11461, Saudi Arabia (e-mail: email@example.com).
Received 6 May, 2012
Accepted 29 July, 2012
The authors report no conflicts of interest.
Objective: The aim of the present study was to investigate the relation between consanguinity and inflammatory bowel diseases (IBD).
Methods: Review of the medical records of children with a final diagnosis of IBD to determine age, sex, and type of IBD, supplemented by information on consanguinity and family history (FH) of IBD in relatives. There were 138 children, ages 1.4 to 19.3 years, and 50% were girls.
Results: The prevalence of consanguinity was 50%, 53%, 39% and 60% in IBD, Crohn disease (CD), ulcerative colitis (UC), and controls, respectively. There was a significantly higher prevalence of consanguinity in controls than in patients with IBD and UC (P = 0.02 and 0.026, respectively), whereas the difference between CD patients and controls was not significant (P = 0.20). The prevalence of first cousin consanguinity was 71%, 73.2%, 61.5% and 70.5% in patients with IBD, CD, UC, and controls, respectively, indicating no significant difference between these conditions and controls (P = 0.95, P = 0.78, P = 0.33, respectively). There was no significant difference in the prevalence of consanguinity in the parents of children with or without a FH of either CD (P = 0.89) or UC (P = 0.32).
Conclusions: There is no significant relation between parental consanguinity and IBD in this population, especially when there is no FH of disease, suggesting reduced genetic susceptibility; however, further studies including larger sample size and details of FH of consanguinity and IBD in multiple generations are needed for further definitions of the role of consanguinity.
Inflammatory bowel diseases (IBD) in the form of Crohn disease (CD) and ulcerative colitis (UC) are more common in whites of the Western world than in other population (1,2). The prevalence is highest in North America and Europe and much lower in Asian countries (3,4). A recent systematic review demonstrated a rising incidence of pediatric-onset IBD worldwide (5). It is generally believed that IBD results from a dysregulated immune response to environmental triggers in genetically susceptible subjects.
It is well known that consanguinity is a risk factor for the development of genetic diseases in general (6). The association of consanguinity with genetic diseases has been reported from many countries with high consanguinity prevalence (7); however, data on the role of consanguinity in multifactorial diseases are scarce. In a cross-sectional population-based study from Qatar, a country with a high consanguinity rate, diabetes mellitus and asthma were more common in the offspring of consanguineous than nonconsanguineous couples (8), whereas reports from our institution found no significant effects of parental consanguinity on the occurrence of asthma or diabetes mellitus in children (9,10). The difference between Kingdom of Saudi Arabia (KSA) and Qatar regarding the role of consanguinity in asthma/diabetes is most probably related to sampling. The KSA sample is representative of the general population, whereas the Qatari sample is a combination of health center and hospital population. In addition, the Qatari sample did not distinguish type 1 from type 2 diabetes mellitus, whereas the KSA sample reported on type 1 diabetes mellitus only. Regarding asthma, a study from the United Arab Emirates, another country with a high prevalence of consanguinity, found no significant difference in the occurrence of asthma between consanguineous and nonconsanguineous groups, a finding that is consistent with ours (11). Celiac disease is another polygenic condition linked to IBD (12). In a study from KSA, 28 of 50 (56%) children ages 10 to 18 years with confirmed celiac disease were product of consanguineous marriage, a figure that is not significantly different from that in the general Saudi population (13).
To our knowledge, the relation between consanguinity and IBD has not been reported. This information is potentially important not only for counseling but also for understanding the role of genetic susceptibility in IBD. Based on most previous studies on the lack of a relation between consanguinity and multifactorial diseases (9–11,13), we hypothesized that there is no relation between consanguinity and IBD.
This is a retrospective-prospective study of all of the pediatric patients with confirmed diagnoses of IBD presenting at younger than 18 years of age at 2 major medical centers in Riyadh, KSA. The first is King Khaled University Hospital, a free-access primary and tertiary care general hospital providing free medical care to Saudi nationals as well as expatriate government employees. The second is Al Mofarreh Poly Clinic, which is one of the leading private gastroenterology outpatient clinics in Riyadh.
The retrospective data collection from medical records included sex, age at symptom onset, age at diagnosis, clinical presentation, laboratory results, imaging, endoscopic and histopathologic studies, and follow-up notes; however, these data were obtained to confirm the final diagnosis of IBD rather than for the purpose of looking at correlations with consanguinity status. Criteria for the diagnosis of UC and CD were based on recommendations of the working groups of the European Society for Pediatric Gastroenterology, Hepatology, and Nutrition (14) and the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition (15). Because data on the family history (FH) of IBD and the consanguinity status of the parents were generally deficient in the medical records, this information was obtained prospectively during clinic visits or by telephone calls. Data retrieval from medical records and prospective collection of information on consanguinity and FH were performed from September 2010 to June 2011.
The data on consanguinity for controls were drawn from the National Health Profile Survey conducted in 2003 and 2004. The study sample was cross-sectional, determined by stratified multistage probability sampling of Saudi households of each region of the KSA; however, because our IBD cohorts were from the region of Riyadh, only the control data from this region were included. Further details have been described previously (16). The Paris classification was used to analyze the age at diagnosis of IBD (17). For patients and controls, the consanguinity status was classified as first-degree cousins, more distant familial relationship or no relationship.
Statistical analyses in the form of descriptive statistics, χ2, or Fisher exact tests were used as appropriate to assess the significance of the relation between consanguinity and IBD and between consanguinity and FH of IBD. A P value below 0.05 was considered significant. The study was approved by the institutional review board of the College of Medicine and King Khaled University Hospital, King Saud University (no. 10/2647/IRB).
From April 1993 (date of starting the service in the 2 centers) to December 2010, 218 children were diagnosed as having IBD, and information on both consanguinity and FH was available for 138 (63%). The remaining patients were not reachable using the available contact information. All of the children were Saudi nationals. A total of 69 children (50%) were girls. The age range at final diagnosis was 1.4 to 19.3 years. One hundred and twenty-eight children with IBD were younger than 17 years at diagnosis, of whom 16 (12.5%) were younger than 10 years. Consanguinity was positive in 4 of 16 (25%) and 29 of 112 (25.9%) in the children younger than 10 years and between 10 and 16 years of age, respectively indicating no significant difference (P = 0.953). There was no significant relation of consanguinity with sex (P = 0.660). Thirteen (9.4%) of the 138 total children were diagnosed between 1993 and 1998, 31 (22.5%) between 1999 and 2004, and 94 (68.1%) between 2005 and 2010.
The consanguinity status was available from the parents of 138 children with IBD, 105 with CD, and 33 with UC, but no cases of IBD-unclassified (IBD-U) were found at the time of final diagnosis. The relation between parental consanguinity and IBD in children is presented in Table 1, indicating positive parental consanguinity in 50%, 53%, 39%, and 60% of children with IBD, CD, UC, and controls, respectively. There was a significantly higher prevalence of positive consanguinity in controls than in patients with IBD and UC (P = 0.02 and 0.026, respectively), whereas the difference in the prevalence of consanguinity between patients with CD and controls was not significant (P = 0.20). Table 2 depicts the relation between first-cousin consanguinity and IBD in children, indicating positive first-cousin consanguinity in 71%, 73.2%, 61.5%, and 70.5% of children with IBD, CD, UC, and controls respectively. There was no significant difference in the prevalence of consanguinity between these conditions and controls (P = 0.95, P = 0.78, P = 0.33, respectively).
Information on the FH of IBD was available for 118 of 138 patients (86%). The relation between FH of IBD and consanguinity is shown in Table 3. A FH of IBD was present in 18 patients (15 CD and 3 UC). The prevalence of consanguinity in patients with CD was 9 of 15 (61%) and 40 of 74 (54%) in patients with and without a FH of disease, respectively, and no significant difference was detected (P = 0.89). Similarly, the prevalence of consanguinity in patients with UC was 2 of 3 (66.7%) and 9 of 26 (34.6%) in patients with or without a FH of disease, respectively, indicating no significant difference (P = 0.32).
The pattern of IBD in this group of children is similar to the larger sample in a previous report (18). The lack of cases of IBD-U in this cohort does not mean they do not exist. This was because the data were collected for the final rather than the initial diagnosis. In fact, reports of the proportion of IBD-U, formerly called indeterminate colitis varied from 7 of 50 (16%) in KSA (19) to 1 of 16 (6%) in Libya (20), whereas no cases of IC were reported among 24 children from Lebanon (21).
Knowledge of the relation between parental consanguinity and IBD in children is important not only for counseling in communities with high prevalence of consanguinity but also as an indirect indicator of genetic susceptibility in the pathogenesis of IBD.
In this report, the 50% prevalence of parental consanguinity in this cohort of children with IBD is lower than the reported 60% prevalence in controls. In addition, the prevalence of first-degree cousin consanguinity, the closest form of consanguinity between husband and wife, was 71%. This was similar to the 70.5% prevalence in controls. These findings are consistent with the historical relation between consanguinity and IBD in this region. This relation is demonstrated by the comparison of the prevalence of consanguinity in the greater Riyadh region reported in 1995 (60.8%) with the 60% prevalence reported in a more recent study in 2007 (16,22), indicating no significant change in the prevalence of consanguinity during a period of >12 years. Interestingly, during this period in this region, there were increasing reports of IBD in children and adults (19,23,24), providing additional support for the lack of relation between consanguinity and IBD.
The 15.3% rate of family aggregation in this exclusively pediatric population of Arab ethnicity is intermediate between Western and Asian populations (25–29). In this report, the higher prevalence of consanguinity in the parents of children with a FH of CD and UC supports the general view that the effect of consanguinity is greater when there is a FH of disease; however, the difference was not significant perhaps because of the relatively small sample size.
There are limitations related to the retrospective nature of the present study. The lack of information on multiple consanguinity patterns, FH of consanguinity, and history of IBD in previous generations are important confounders that may have affected the results. The importance of detailed FH of both consanguinity and IBD in as many generations as possible is considerable. Multiple consanguinity and consanguinity in previous generations in a pedigree are additional risk factors to the background risk in a single generation (30). These may lead not only to identification of genetic defects but also to characterize the mode of inheritance. Another possible confounder is the effect of social classes on consanguinity and IBD, which is not available in the present study or previous publications on IBD in the KSA.
It can be concluded that there is no significant relation between parental consanguinity and IBD in this population, especially when there is no FH of disease, suggesting reduced genetic susceptibility; however, further studies including larger sample size and details of FH of consanguinity and IBD in multiple generations are needed for further definitions of the role of consanguinity.
The authors thank the Vice-Rectorship for Post-graduate and Scientific Research, King Saud University, for continuous support, as well as Dr Shafie Shaikh, Department of Community Medicine, King Saud University, for statistical assistance.
1. Loftus EV. Clinical epidemiology of inflammatory bowel disease: Incidence, prevalence, and environmental influences. Gastroenterology
2. Kugathasan S, Judd RH, Hoffmann RG, et al. Epidemiologic and clinical characteristics of children with newly diagnosed inflammatory bowel disease in Wisconsin: a statewide population-based study. J Pediatr
3. Farrokhyar F, Swarbrick ET, Irvine EJ. A critical review of epidemiological studies in inflammatory bowel disease. Scan J Gastroenterology
4. Yang SK, Loftus EV Jr, Sandborn WJ. Epidemiology of inflammatory bowel disease in Asia. Inflamm Bowel Dis
5. Benchimol EI, Fortinsky KJ, Gozdyra P, et al. Epidemiology of pediatric inflammatory bowel disease: a systematic review of international trends. Inflamm Bowel Dis
6. Bittles AH. Consanguinity and its relevance to clinical genetics. Clin Genet
7. Al-Gazali L, Hammami H, Al Arrayad S. Genetic disorders in the Arab world. Br Med J
8. Bener A, Hussain R. Consanguineous unions and child health in the State of Qatar. Paediatr Perinat Epidemiol
9. El Mouzan MI, Al Salloum AA, Al Herbish AS, et al. Consanguinity and major genetic disorders in Saudi children; a community-based cross-sectional study. Ann Saudi Med
10. El Mouzan MI, Al Salloum AA, Al Herbish AS, et al. Does consanguinity increase the risk of bronchial asthma in children? Ann Thoracic Med
11. Abdulrazzaq YM, Bener A, Al-Gazali LI, et al. A study of possible deleterious effects of consanguinity. Clin Gen
12. Lees CW, Barrett JC, Barkes M, et al. New IBD genetics. Gut
13. Ouda S, Saadah O, El Meligy O, et al. Genetic and dental study of patients with celiac disease. J Clin Pediatr Dent
14. Escher JC, Amil Dias J, Bochenek K, et al. Inflammatory bowel disease in children and adolescents: recommendations for diagnosis—The Porto Criteria. IBD Working Group of the European Society for Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN). J Pediatr Gastroenterol Nutr
15. Bousvaros A, Antonioli DA, Colletti RB, et al. Differentiating ulcerative colitis from crohn disease in children and young adults: report of a Working Group of the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition and the Crohn's and Colitis Foundation of America. J Pediatr Gastroenterol Nutr
16. El Mouzan MI, Al-Salloum AA, Al-Herbish AS, et al. Regional variations of consanguinity in Saudi Arabia. Saudi med J
17. Levine A, Griffiths A, Markovitz J, et al. Pediatric modification of the Montrial classification for inflammatory bowel disease: the Paris classification. Inflamm Bowel Dis
18. El Mouzan MI, Al Mofarreh MA, Assiri AM, et al. Presenting features of childhood-onset inflammatory bowel disease in the central region of of Saudi Arabia. Saudi Med J
19. El Mouzan MI, Abdullah AM, Al Habbal MT. Epidemiology of juvenile-onset inflammatory bowel disease in Central Saudi Arabia. J Trop Pediatr
20. Ahmaida A, Al Shaikhi S. Childhood IBD in Libya: epidemiological and clinical features. Libyan J Med
21. Abdul-Baki H, ElHajj I, El-Zahabi LMN, et al. Clinical epidemiology of inflammatory bowel disease in Lebanon. Inflamm Bowel Dis
22. El-Hazmi MA, Al-Swailem AR, Warsy AS, et al. Consanguinity among the Saudi Arabian population. J Med Genet
23. Isbister WH, Hubler M. Inflammatory bowel disease in Saudi Arabia: presentation and initial management. J Gastroenterol Hepatol
24. Al-Mofarreh MA, Al Mofleh IA, Al-Teimi IN, et al. Crohn's disease in a Saudi outpatient population: is it still rare. Saudi J Gastroenterol
25. Polito JM 2nd, Childs B, Mellits ED, et al. Crohn's disease: influence of age at diagnosis on site and clinical type of disease. Gastroenterology
26. Griffiths AM. Specificities of inflammatory bowel disease in childhood. Best Pract Res Clin Gastroenterol
27. Chattani HK, Nigam SB, Sama SK, et al. Ulcerative colitis in the tropics. Br Med J
28. Kitahora T, Utsunomiya T, Yokota A. Epidemiological study of ulcerative colitis in Japan: incidence and familial occurrence. The Epidemiology Group of the Research Committee of Inflammatory Bowel Disease in Japan. J Gastroenterol
1995; 30 (suppl 8):5–8.
29. Park JP, Yang SK, Byeon JK, et al. Familial occurrence of inflammatory bowel disease in Korea. Inflamm Bowel Dis
30. Lewis R. Human Genetics: Concepts and Application
. New York: McGraw Hill; 2005.
consanguinity; Crohn disease; ulcerative colitis
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