We have investigated the prevalence of a recently reported genetic variation in the prothrombin gene (G20210A) in patients with an objectively confirmed history of venous thrombosis. 12/219 patients (5.5%) were found to be heterozygous carriers of the 20210 A allele. The incidence of the 20210 A allele in a group of 164 healthy controls was 1.2% (allele frequency 0.61%, 95% CI 0.08–2.19). When patients with a known alternative hereditary risk factor for venous thrombosis (factor V Leiden mutation or deficiency of antithrombin, protein C or protein S) were excluded, the G20210A variant was found to increase the risk for venous thrombosis by approximately 5‐fold (odds ratio 5.4, 95% CI 1.16–25.0). This prothrombin gene sequence variation adds further to the list of recognized genetic risk factors for thrombophilia.

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Objective. To assess whether the HLA—DR4 association found in rheumatoid arthritis (RA) is also seen in the large granular lymphocyte (LGL) syndrome. Methods. HLA—DR genotyping was performed using restriction fragment length polymorphism and polymerase chain reaction analysis. Results. LGL syndrome patients with RA showed the same HLA–DR4 association seen in RA/Felty's syndrome (FS), while LGL syndrome patients without arthritis did not. Conclusion. It is proposed that FS and the LGL syndrome represent different variants of a broader syndrome comprising RA, neutropenia, LGL expansions, HLA—DR4 positivity, and splenomegaly.

Background-In the UK approximately 1 in 140 people are homozygous for the C282Y mutation of the HFE gene and are at risk from iron overload caused by genetic haemochromatosis (GH). Early detection can prevent organ damage secondary to iron deposition and increase life expectancy. Aim-To screen for GH in all blood samples sent to the laboratory for routine liver function tests in which raised serum alanine aminotransferase (ALT) activity was detected. Methods-ALT was measured in sera sent to the laboratory for routine liver function tests. In those samples found to have raised activity, transferrin saturation and ferritin were measured followed by genetic testing when transferrin saturation was increased. Results-Of the 35 069 serum samples assayed for routine liver function tests, 1490 (4.2%) had raised ALT levels (>50 u/l). Transferrin saturation and serum ferritin concentrations were measured in these patient samples, and in 56 transferrin saturation was >60%. Further blood samples were requested from these patients for genetic testing: 33 samples were obtained. There were nine patients homozygous for the C282Y mutation of the HFE gene and three compound heterozygotes (heterozygous for both C282Y and H63D mutations). Conclusions-The association of raised ALT activity and transferrin saturation of >60% could provide a simple, cost eVective method for detecting individuals with clinical haemochromatosis. Although many patients with GH may have been missed, this study suggests that the clinical penetrance of the disorder may be much lower than is generally supposed and that genetic screening will identify many people who may never develop clinical haemochromatosis. (Gut 2000;46:707-710)