Interethnic variation in genetic risk factors for vascular disease

Genetic predisposition to vascular disease has important implications for population screening and prevention. The most common hereditary cause of venous thrombosis is resistance to activated protein C caused by the G1691A point mutation in exon 10 of the factor V gene (1q21-25) which leads to the substitution of glutamine for arginine (factor V Leiden). A thermolabile variant of 5, 10-methylenetetrahydrofolate reductase (MTHFR) caused by the C677T mutation of the MTHFR gene (1p36.3) which substitutes valine for alanine is associated with the vascular disease risk factor hyperhomocysteinaemia. The possibility that these mutations may predispose individuals of African-American origin to thrombosis was investigated in 9 patients (6 male, 3 female) with sickle cell anaemia who had experienced a thrombotic episode. The frequency of the MTHFR C677T mutation was also determined in unrelated subjects from six different populations: African-Caribbean (50), Oriental (47), Asian Indian (21), Middle Eastern (24), Meditteranean (50) and Northen European (61). The MTHFR and factor gene regions of interest were amplified by the polymerase chain reaction method. Factor V Leiden was screened for by single strand conformation polymorphism analysis and the MTHFR C 677T mutation by Hinf 1 restriction. All patients were homozygous normal (G/G) for the factor V allele. This is consistent with population studies which failed to identify factor V Leiden in normal subjects of Sub-Saharan African populations and found a low frequency (0.65 percent in Black Americans. By contrasts, factor V Leiden was found to be most prevalent in European populations (from 1.4 percent in Finland to 7 percent in Greece). One patient was heterozygous (C/T) and 8 homozygous normal (C/C) for the MTHFR mutation. Population studies revealed the observed frequency of the mutant allele (T) to be lowest in African-Caribbean subjects (9 percent) of whom none were homozygous and only 18 percent heterozygous. The frequency was highest in the Meditteranean population (42 percent), followed by Middle Eastern (38 percent), Northern European (30 percent), Asian Indian (21 percent) and Oriental (19 percent). No deviation from Hardy-Weinberg equilibrium was detected. The proportion of subjects homozygous for the mutation (T/T) was 18 percent Meditteranean, 17 percent Middle East, 10 percent Northern European and Asian Indian and 2 percent Oriental. (AU)

Effect of fetal diagnostic testing on birth-rate of thalassaemia major in Britain.

A programme of prospective heterozygote detection and counselling, fetal diagnostic testing, and abortion of fetuses affected by thalassaemia major introduced in Britain in 1977 has proved highly acceptable to at-risk couples of Cypriot and East African Asian origin, but less so to couples of Pakistani origin. However, many at-risk couples are still not detected prospectively, the proportion of thalassaemia-major births prevented was only 32% by the end of 1981, and there is little evidence of a further fall since then. The thalassaemia-major birth-rate had fallen by 60% in Cypriots and by 20% in East African Asians, but it had not fallen at all in Pakistanis. Improved approaches to fetal diagnosis of thalassaemia major are becoming available, so a concerted effort is needed to inform all the at-risk ethnic groups of the existence of the problem and the possibility of detection of affected fetuses.

Carcinoembryonic antigen and humoral antibody response in patients with thyroid carcinoma.

Carcinoembryonic antigen and antibodies to thyroglobulin and to a microsomal fraction of thyroid were measured. Persons examined were normal volunteers, patients with thyroid cancer, and patients with a history of childhood irradiation to the thymus and/or tonsil who were otherwise normal. Elevated antigen and antibodies were most frequently found in the cancer thyroid group. Thyroid cancer patients with no previous history of childhood irradiation were more frequently positive for antigen and antibodies than all other categories studied. Thyroid cancer patients with a previous history of childhood irradiation showed normal frequencies of antigen and antibodies. The results suggest that the antigenic expression and host response to the tumor in patients with thyroid cancer depend on its pathogenesis. Mention is made of similar findings in animal model systems.