Appendicitis usually afflicts the young, but there is a large tail in the distribution of onset age. The genetics of this disease are still not well understood. A heritability analysis and genome wide linkage analysis of a large twin dataset was undertaken. Treating age of onset of appendicitis as a censored survival trait revealed a heritability of 0.21, and found evidence of linkage to Chromosome 1p37.3.

A retrospective study was performed to identify factors associated with perforation in 150 children with acute appendicitis. The children's parents were interviewed about the nature and timing of care, family history of appendicitis, and history of abdominal pain episodes, and the children's medical records were reviewed. Delay in treatment--the interval between first recognized symptoms of abdominal pain and surgery--was most predictive of perforation. A treatment delay of more than 36 hours was associated with a 65% or greater incidence of perforation. Mean delay for the group with perforation of the appendix was 66.7 hours compared with 35.8 hours for the group having appendicitis without perforation (P less than .01). Mean professional delay was significantly longer in the group with perforated appendicitis than in the group having appendicitis without perforation (P less than .01), but mean parental delay was not. Children aged 1 to 4 years and those aged 5 to 8 years had a 74% and 66% incidence of perforation, respectively, compared with a 30% to 42% incidence in older children (P less than .01). Age had a significant effect upon perforation even when adjusted for delay in treatment. Other factors associated with perforation were family history of appendicitis, social class, advice given by the first health professional contacted, and the presence of fecaliths. When all factors were considered simultaneously by using logistic regression techniques, delay in treatment, age, and absence of a family history of appendicitis were all significant predictors of perforation.

OBJECTIVE: Using acute appendicitis as a model, we tested the hypothesis that polymorphisms in genes involved in host defense can be associated with the severity of local infection-inflammation in humans. SUMMARY BACKGROUND DATA: Innate immunity is the body's front-line system for antimicrobial host defense. Local inflammation is a major innate immune mechanism for containing and destroying microbes, but it may also contribute to tissue injury. METHODS: We studied 134 patients with acute appendicitis treated at an urban hospital. We looked for associations between the severity of appendicitis (uncomplicated vs. perforated or gangrenous), plasma and peritoneal cytokine concentrations, and single nucleotide polymorphisms in genes involved in recognizing bacterial molecules [CD14 (-159 C-->T); TLR4 (896 A-->G)] and in mounting an inflammatory response [IL-6 (-174 G-->C), TNF-alpha (-308 G-->A), IL-1beta (-31 C -->T)]. RESULTS: Ninety-one patients (68%) had uncomplicated appendicitis and 43 (32%) had complicated disease. The SNPs in the CD14, TLR4, IL-1beta, and TNF-alpha genes were not associated with the severity of appendicitis. A strong association was found between C-allele carriage at -174 in the IL-6 gene and decreased risk of complicated disease (adjusted odds ratio = 0.24, 95% CI = 0.07-0.76). Lower plasma and peritoneal fluid IL-6 concentrations in the IL-6 -174 C-carriers than in the GG homozygotes suggest that this polymorphism contributes to decreased IL-6 production in vivo. CONCLUSIONS: Polymorphism in the IL-6 gene was associated with the severity of appendicitis, even after adjustment for duration of symptoms. The risk for developing appendiceal perforation or gangrene may be determined, in part, by variation in the IL-6 gene.

We explored familiality as well as the heritability and possible mode(s) of inheritance of acute appendicitis in childhood and early adolescence. Our case-control study showed that a positive family history for reported appendectomy was significantly more frequent in families of 80 consecutive patients eventually proved to have histopathologic acute appendicitis than in families of surgical controls matched for sex, age, and number of siblings. The relative risk was 10.0 (95% confidence limits 4.7-21.4). The pattern of familial aggregation was further supported by the fact that the age-standardized morbidity ratio was four times greater among family members of cases than among controls. We then applied the unified mixed model of segregation analysis, as implemented in the computer program POINTER, to a new set of 100 multigenerational pedigrees of children with histopathologically confirmed acute appendicitis that were broken down into 674 nuclear families. Age-specific morbidity risk and lifetime incidence of acute appendicitis were estimated from relatives of controls matched for age and sex to probands. Complex segregation analysis supported a polygenic or multifactorial model with a total heritability of 56%. There was no evidence to support a major gene, although a rare gene could not be ruled out as the cause of a small proportion of cases. Specific studies to address genetic and environmental factors in this serious disease seem worthwhile; but, for now, a positive family history of appendicitis might join other evidence leading to improved clinical recognition of acute appendicitis.

Although inflammatory disease of the vermiform appendix has been recognized as such for more than 100 years, its aetiology remains a subject of controversy. Since early this century consumption of a low fibre diet has been implicated. More recently this theory has been challenged and the role of infection emphasized.

A family history of appendicectomy was sought in two groups of children admitted to Llandough Hospital over sixteen months. The study group consisted of 29 children with histologically confirmed acute appendicitis, while the control group consisted of 29 children admitted for reasons unrelated to abdominal pain. A history of appendicectomy was elicited in first-degree relatives--that is, siblings and parents of 20 of the children in the study group and of four of the controls--a statistically significant difference. The results obtained from this study suggest that a familial predisposition to appendicitis exists.

The widely accepted negative association between schizophrenia and rheumatoid arthritis (RA) is based on the results of investigations which sought RA in large samples of schizophrenic patients. Using a discharge register, we examined the frequency of schizophrenia in a sample of 5626 RA patients. Appendicitis patients (n = 5330) were used as a comparison group. The cumulative incidence of hospital care with the diagnosis of schizophrenia during 8 years was higher in the RA group (0.64%) than in the appendicitis group (0.47%). Schizophrenia was significantly more common in the RA group than in the appendicitis group among the young. The age-adjusted prevalence of schizophrenia was 0.96% in the RA group and 0.51% in the appendicitis group. Because of this unexpected finding, we examined the incidence of RA and appendicitis among a birth cohort born in 1966. The frequencies of RA and appendicitis among schizophrenic cohort members (n = 76), cohort members with psychiatric diagnosis other than schizophrenia (n = 438), and members without psychiatric diagnosis (n = 10503) were similar. These findings do not support the negative association between schizophrenia and RA. Prolonged institutionalization per se may have been the protective factor against RA in the previous studies. The findings also raise the hypothesis that genes that predispose to schizophrenia provide protection from appendicitis, historically a common cause of mortality.