Familial Constipation Is Associated with α2 Adrenoceptor Polymorphism

Abstract

Background: We have previously showed the presence of familial aggregation in patients with functional constipation. Genetic factors may be an underlying etiology. It has been reported that α2a and α2c adrenoceptor polymorphisms were associated with irritable bowel syndrome with predominant constipation. Aim: to investigate if α2a and α2c adrenoceptor polymorphisms are associated with familial constipation. Methods: Patients with functional constipation satisfying the Rome II criteria were recruited. The presence of functional constipation in their family members were enquired as described in our previous study. Polymorphisms for α2 adrenoceptor were detected by polymerase chain reaction amplification, and sequencing. Familial constipation was arbitrarily defined as the presence of ≥3 first degree relatives with functional constipation. Results: There were 46 patients with familial constipation and 151 without. The two groups did not differ in age (48 ± 12 vs 47 ± 12 years, p=0.45), but more female were observed in the familial group (93.5% vs 79.5%, p= 0.017). The prevalence of α2A-1291 (C→G) wild-type was 10.7%, heterozygous 46.2% and homozygous polymorphism 43.1%, and α2CDel 322-325 wild-type 77.2%, heterozygous 16.8% and homozygous polymorphism 6.1%. There was no association between α2A polymorphism and familial constipation, or between α2C polymorphism and familial constipation. However, there were more patients with familial constipation having the combined genotype of α2CDel 322-325 homozygous and α2A-1291 (C→G) heterozygous/homozygous polymorphism (10.9% vs 3.3%, p=0.041). Conclusion: Familial constipation is associated with α2 adrenoceptor polymorphism. Genetic factor may play an important etiological role in familial constipation.