Polymorphism in apoprotein-CIII gene and coronary heart disease.

BACKGROUND: The aim of this study was to look into the association, if any, of apoprotein-CIII variant allele with hypertriglyceridemia, hypercholesterolemia and coronary heart disease (CHD). PATIENTS AND METHODS: The prevalence of a C to G substitution in the 3' untranslated region of apoprotein-CIII was studied in a sample of 92 angiographed Saudi subjects, consisting of 65 males and 27 females. The subjects were genotyped by amplification followed by digestion of the gene fragment containing the polymorphic site with Sac I restriction enzyme. RESULTS: The variant allele of apoprotein-CIII was found to be associated neither with hypertriglyceridemia nor with hypercholesterolemia. However, a significant association of this allele (P<0.01) was found with coronary heart disease, independent of other risk factors such as smoking, diabetes and hypertension. An estimation of odds ratio using logistic regression with various risk factors in the model showed that the individuals with this rare allele were 3.4 times more at risk of developing coronary heart disease. This estimate of risk held even after analyzing a subset of individuals above 45 years of age. CONCLUSION: While the association between apoprotein-CIII variant allele and dyslipidemia could not be established in this study, the relationship between this marker and CHD was highlighted in the studied subjects.

Primary hyperparathyroidism-associated polyostotic fibrous dysplasia: absence of McCune-Albright syndrome mutations.

Several cases of sporadic primary hyperparathyroidism in association with fibrous dysplasia of the bone have been reported in the English literature. Since fibrous dysplasia is a major feature and hyperparathyroidism is occasionally found in the McCune-Albright syndrome, we hypothesized that such cases may represent a variant of this syndrome. A 28-year-old male had primary hyperparathyroidism associated with polyostotic fibrous dysplasia but no other manifestations of the McCune-Albright syndrome. Genomic DNA samples from his parathyroid adenoma, dysplastic bone sample, and peripheral leukocytes were analyzed for the presence of activating mutations of the stimulating G protein alpha subunit gene (gsp). Allele-specific hybridization revealed the presence of normal sequences only, coding for arginine and glutamine at codons 201 (exon 8) and 227 (exon 9), respectively. Further, single strand conformational analysis of a 224 base pair fragment of exon 8 revealed no conformational aberrations. Furthermore, the sequences of a 164 base pair fragment of exon 8 and a 170 base pair fragment of exon 9 were normal. The results strongly suggest that gsp mutation is absent in affected and normal tissues in this patient and that the association of hyperparathyroidism and fibrous dysplasia may not represent a variant of the McCune-Albright syndrome.

HLA-DR types in rheumatic, congenital and degenerative cardiac valve diseases in Saudi patients.

Subjects of Saudi origin were DNA typed for HLA-DR2, DR4 and DRw53 by amplification fragment-length polymorphism and amplification by sequence-specific primer techniques based on polymerase chain reaction. Of these subjects, 125 had sporadic heart valve disease (96 with rheumatic heart disease, 18 with degenerate and 11 with congenital degenerate valve disease) and 77 were healthy Saudi blood donors. While the frequency of individuals typed DR4 was about the same in the rheumatic heart disease as in the control category (30% versus 23%, respectively), it was found to be higher (55%; P<0.02), but below the level of marginal significance after correcting for the number of DR types, in the congenital degenerate valve category. No preferential association of any DR4 subtype could be detected. The incidence of DR2 was lower in the congenital cases compared to that in the controls (9% versus 21%) and remained about the same in the rheumatic heart disease patients as in the controls. The frequency of DRw53 in the degenerate valve categories was slightly lower than that in the controls, but the difference was not significant. The study failed to corroborate the association between HLA-DR4 and rheumatic heart disease shown in previous studies using the serotyping approach.

Determination of haemophilia A carrier status from hair samples using polymerase chain reaction technique.

The usefulness of intragenic restriction fragment length polymorphisms (RFLPs) for BclI, HindIII and XbaI, adapted for polymerase chain reaction (PCR), was tested for the detection of haemophilia A carrier status in the consultant of a family in which only haematological information was available on the inheritance of the trait. Hair follicles were used as the non-invasive source of DNA. The mother was found to be homozygous for BclI and heterozygous for HindIII sites, whereas her status as regards informativeness could not be established for XbaI. On the basis of HindIII RFLP, the daughter was found to be a carrier of the haemophilia trait. This was confirmed by sequencing the amplified intron 19 of the mother and the daughter. The RFLP for XbaI did not appear to be suitable for carrier detection using PCR due to the difficulty of establishing homozygosity or heterozygosity from the results of digestion of the amplified product.

Restriction fragment length polymorphisms in the ETS-1 proto-oncogene. Comparison of Saudi and Western populations.

We have cloned part of the ETS 1 proto-oncogene and demonstrated the presence of two polymorphic Sst I restriction sites. A probe derived from one of our clones revealed the presence of 8.3 kb, 9.5 kb and/or 11.5 kb fragments on Southern blots of human DNA samples. The relative frequencies of these alleles appear to be significantly different between Saudi and Western populations, but there are no apparent differences in these frequencies between Saudi non-leukemic and leukemic individuals.