MDR1C3435T Polymorphism and Inflammatory Bowel Disease

Sir,

Inflammatory bowel disease (IBD) is a broad term that describes conditions with chronic or recurring immune response and inflammation of the gastrointestinal tract. The two forms of IBDs are ulcerative colitis (UC) and Crohn's disease (CD). Inflammation affects the entire digestive tract in CD and only the large intestine in C. Both illnesses are characterized by an abnormal response of the body's immune system of an unrecognized trigger.

IBD is characterized by abdominal pain, diarrhea, rectal bleeding, and weight loss.[1] Both UC and CD have a complex etiology involving multiple genetic factors, environmental factors, and immune dysregulations.[2] Environmental factors such as cigarette smoking, dietary components, infectious microbes, sanitation, and hygiene or contact with pets remarkably increase the incidence of IBD.[3,4] Involvement of genetic factors in the IBD pathogenesis has been confirmed by the observations performed on mono- and dizygotic twins and familial aggregation of the disease. In addition, a positive family history is still the largest independent risk factor for the disease.[4,5,6,7,8,9,10,11] The results of studies on the human genome demonstrated that the human multidrug resistance 1 gene (MDR1) is the most likely locus to be associated with susceptibility to IBD.[12,13,14]

Bonyadi and co-workers assessed the association of MDR1 C3435T polymorphism with IBD.[15] The study aimed to evaluate the impact of the MDR1 C3435T polymorphism on IBD. Although the study provides preliminary evidence to consider MDR1 C3435T polymorphism as a risk factor for IBD, after careful reading of the article, few important issues came out which must be addressed for further actions. First, it appears that the authors somehow missed the statistical power in this study. Sample sizes remain a major issue in genetic case–control studies analyzing the association of polymorphism with disease susceptibility. Hence, the study should obtain an adequate statistical power to estimate significant association accurately, which remains a primary criterion to perform such studies. Underpowered studies usually lead to false-positive associations and misinterpretations.[16] The authors failed to mention the incidence rate of IBD in the said study, which is necessary for sample size calculation. The author has failed to mention whether the number of patients and controls recruited in the present study has achieved the required statistical power (80%). Furthermore, restriction sequence (rs) number of the MDR1 C3435T polymorphism should be mentioned in the manuscript to increase the readability and scientific presentation of the manuscript. All these points suggest a thorough examination of the observed association prior to concluding that MDR1 C3435T gene polymorphism is a potential marker of IBD.

All together, these data are very interesting and warrant further large-scale, case-controlled studies of MDR1 C3435T polymorphism as a biomarker to predict the risk of developing IBD. Treatment of IBD is expected to evolve with the strides made in molecular diagnostics and targeted therapy. Commonly occurring SNPs should be meticulously studied in populations where there is paucity of such data, to learn more about the molecular signature of the disease.