G Protein Beta3Subunit And Catechol-o-methyltransferase Gene Polymorphisms In Elderly Patients With Irritable Bowel Syndrome

Background and objective:Irritable bowel syndrome (IBS) is a common chronic functional intestinal disease. In recent years, the incidence increased gradually, which was10%?20%in Europe and North America according to previous reports, while the incidence in Asian countries was5%-10%. As was reported, the prevalence in elderly people was relatively high. So far, the pathogenesis of IBS has not been fully clarified. Rare investigation was focused on the elderly counterpart of IBS pathogenesis. At present, the study of genetic polymorphism has become a new hotspot in the research area of the IBS.G proteins are one of the second messengers which consist of three different subunits, namely ?,? and ?. Each subunit of the functional disorders can affect the intracellular signal transduction. Several investigations reported the relationship between G protein ?3subunit (GNB3) C825T gene polymorphism and IBS. Catechol-O-methyl transferase enzyme (catechol-O-methytransferase, COMT) is one of the metabolic enzymes in human body, which plays a vital role in degradation of catecholamines (such as dopamine, norepinephrine and epinephrine). A Swedish study found that the gene polymorphism of the COMT gene val158met sites was associated with IBS. The above research was only for adults with IBS. Little evidence existed about the gene polymorphism specifically targeted at older age groups with IBS.This study aims to investigate the association between polymorphisms of GNB3, COMT and IBS in Chinese elderly patients, the results of which may provide objective theoretical evidence for detection of susceptible elderly populations with IBS. Subjects and Methods:The IBS group comprised66outpatients and hospitalized elderly patients, who fulfilled the Rome III criteria for IBS. The included patients were divided into three subgroups according to the classification of IBS:(1) the constipation type (IBS-C);(2) the diarrhea type (IBS-D);(3) the mix type (IBS-M). Control group consists of115outpatients or in-patients during the same period of IBS group. The demographic character was comparable between two groups. All the included patients aged above60years old.Data collection and geriatric depression scale (GDS) test was performed in all the participants. Blood samples were taken from peripheral venous. DNA was extracted from whole blood with standard techniques and kit for DNA extracted.The Taqman technology was used to detect SNP and analysis polymorphisms of GNB3C825T and val158met COMT. Distribution of the difference of genotype and allele frequency between IBS group and the control or between IBS subgroup and control group was analyzed using chi-square test. The Fisher's exact test and chi-square test was used to compare the relationship between the genotypes and the symptoms of abdominal pain, disease duration of IBS. P<0.05was considered to be statistically significant.Results:No significant difference was found in terms of marital status and GDS score between IBS group and control group.In IBS group, genotype percentage of CC, CT and TT in gene GNB3C825T was75.8%,19.7%and4.5%, respectively. In the meanwhile, the percentage in the control group was80%,18.3%and1.7%, respectively. There was no significant difference in genotype distribution between two groups (P=0.512). We also found no significant difference as to allele frequency between the IBS group and control group (P=0.323).In IBS group, genotype percentage of val/val, val/met and met/met in gene COMT was86.4%,1.5%and12.1%, respectively. In the meanwhile, the percentage in the control group was87.8%,11.3%and0.9%, respectively. There was significant difference in val158met genotype distribution between two groups. Significant difference was also found as to allele frequency between the IBS group and control group (P<0.001). Specifically, the frequency of met allele was significantly higher in IBS than that in the control group (P=0.040)In IBS group, three subtypes, namely IBS-D?IBS-M?IBS-C, account for69.7%,69.7%and10.6%respectively. The difference in both genotype distribution and allele frequency between each subtype of IBS and control group was not significant.Significant difference in genotype distribution of COMT val158met was found between IBS-D group,but not IBS-C or IBS-M, and control group (P=0.001). The frequency of met allele was higher, but not significantly, than the control group. The frequency of met allele and val allele was not significantly different between either IBS-C group or IBS-M group.No significant difference in genotype distribution and frequency of allele was found between mild-abdominal-pain group and severe-abdominal-pain group.In IBS group,39.4%of IBS patients suffered more than5years. The patients were divided into two groups according to the course of the disease (no less than5years or less than5years). No significant difference in GNB3genotype distribution and frequency of allele was found between the two groups. The frequency of met allele was higher in IBS patients with disease course no less than5years.Conclusion:In the elderly population in china, GNB3C825T polymorphism and the onset of IBS shows no relevance. Val158met COMT gene polymorphism is associated with susceptibility of IBS. Met allele carriers may be susceptible to IBS.COMT val158met polymorphism is associated with susceptibility of IBS-D. Met allele carriers may be susceptible to diarrhea type of IBS.The severity of abdominal pain in IBS patient has no link to either GNB3C825T or COMT polymorphisms.GNB3C825T polymorphism has no relationship with the course of IBS. Met allele of COMT vall58met has correlation with the duration of IBS. Met allele carriers are likely in a longer duration.