Vanishing bile duct syndrome associated with azithromycin in a 62-year-old man.

Vanishing bile duct syndrome is a severe cholestatic disease associated with toxic effects of medications. Stevens-Johnson syndrome is a hypersensitivity disorder that may also be caused by medications. We present a case of a 62-year-old male patient who developed vanishing bile duct syndrome a month after Stevens-Johnson syndrome. These adverse drug reactions were associated with the use of azithromycin (500 mg daily for 3 days). The patient was initially treated for Stevens-Johnson syndrome with steroids, antihistamines and proton pump inhibitors and fully recovered. However, a month after the beginning of Stevens-Johnson syndrome, he developed vanishing bile duct syndrome and was treated with steroids, ursodeoxycholic acid, antihistamines and tacrolimus. Unfortunately, the treatment was unsuccessful and he was listed for liver transplantation which was performed 7 months after the beginning of jaundice. This is the first case of vanishing bile duct syndrome associated with the use of azithromycin and one of few that reports vanishing bile duct syndrome and Stevens-Johnson syndrome co-occurrence.

Genetic comparison of a Croatian isolate and CEPH European founders.

Human isolates have been postulated as a good resource for the identification of QTL due to reduced genetic diversity and a more homogeneous environment. Isolates may also have increased linkage disequilibrium (LD) due to small effective population size and, either loss or increase in frequency of alleles that are rare in the general population from which they originate. Here we investigate the difference in allele and genotype frequencies, LD and homozygous tracts between an isolate-several villages from the island of Vis in Croatia-and an outbred population of European origin: the Hapmap CEPH founders. Using the HumanHap300 v1 Genotyping BeadChip, we show that our population does not differ greatly from the reference CEU outbred population despite having a slightly higher proportion of monomorphic loci, a slightly higher long-range LD, and a greater proportion of individuals with long homozygous tracts. We conclude that genotyping arrays should perform equally well in our isolate as in outbred European populations for disease mapping studies and that SNP-trait associations discovered in our well-characterized Croatian isolate should be valid in the general European population from which they descend.

Genome-wide association study of anthropometric traits in Korcula Island, Croatia.

AIM: To identify genetic variants underlying six anthropometric traits: body height, body weight, body mass index, brachial circumference, waist circumference, and hip circumference, using a genome-wide association study. METHODS: The study was carried out in the isolated population of the island of Korcula, Croatia, with 898 adult examinees who participated in the larger DNA-based genetic epidemiological study in 2007. Anthropometric measurements followed standard internationally accepted procedures. Examinees were genotyped using HumanHap 370CNV chip by Illumina, with a genome-wide scan containing 316730 single nucleotide polymorphisms (SNP). RESULTS: A total of 11 SNPs were associated with the investigated traits at the level of P<10(-5), with one SNP (rs7792939 in gene zinc finger protein 498, ZNF498) associated with body weight, hip circumference, and brachial circumference (P=3.59-5.73 x 10(-6)), and another one (rs157350 in gene delta-sarcoglycan, SGCD) with both brachial and hip circumference (P=3.70-6.08 x 10(-6). Variants in CRIM1, a gene regulating delivery of bone morphogenetic proteins to the cell surface, and ITGA1, involved in the regulation of mesenchymal stem cell proliferation and cartilage production, were also associated with brachial circumference (P=7.82 and 9.68 x 10(-6), respectively) and represent interesting functional candidates. Other associations involved those between genes SEZ6L2 and MAX and waist circumference, XTP6 and brachial circumference, and AMPA1/GRIA1 and height. CONCLUSION: Although the study was underpowered for the reported associations to reach formal threshold of genome-wide significance under the assumption of independent multiple testing, the consistency of association between the 2 variants and a set of anthropometric traits makes CRIM1 and ITGA1 highly interesting for further replication and functional follow-up. Increased linkage disequilibrium between the used markers in an isolated population makes the formal significance threshold overly stringent, and changed allele frequencies in isolate population may contribute to identifying variants that would not be easily identified in large outbred populations.