Molecular genetic analysis of the alpha-synuclein and the parkin gene in Parkinson's disease in Finland.

Two mutations in the alpha-synuclein gene and various mutations in the parkin gene are associated with familial Parkinson's disease (PD). The present study was performed to analyse if mutations in these genes could be detected in Finnish patients with familial PD. The subjects comprised 22 unrelated patients with familial PD. The molecular genetic analysis consisted of sequence analysis of the non-coding and coding exons of the alpha-synuclein gene and screening of eight point mutations in the parkin gene. In addition, a total of 67 controls and 45 patients with sporadic PD were included in the association analysis on polymorphism of the alpha-synuclein gene. Screened point mutations in the parkin gene were not detected. Sequencing of the coding exons 2-6 of the alpha-synuclein gene did not reveal any mutations or polymorphisms. However, three novel alterations in the T10A7 sequence at the 5' end of the non-coding exon 1' of the alpha-synuclein gene were found. The frequencies of the exon 1' polymorphic genotypes or alleles between familial PD patients and control subjects revealed no statistically significant differences. No association for sporadic PD was observed. The results do not support a role for the alpha-synuclein gene or point mutations of the parkin gene in familial PD in our sample.

Insertion-deletion polymorphism in the gene for angiotensin-converting enzyme is associated with obstetric cholestasis but not with preeclampsia.

OBJECTIVE: Our purpose was to investigate the contribution of angiotensin-converting enzyme insertion-deletion polymorphism in the development of obstetric complications. STUDY DESIGN: In a retrospective case-control study, angiotensin-converting enzyme insertion-deletion polymorphism was investigated in a control group of healthy women (n = 115) and in a group of women diagnosed with preeclampsia (n = 133) and obstetric cholestasis (n = 57). Polymerase chain reaction detection of insertion-deletion polymorphism was used to determine the presence of the two angiotensin-converting enzyme alleles in the groups; the frequencies in the general population in our area are presented for comparison. RESULTS: The frequency of the D allele was 43.9% among women with obstetric cholestasis and 27% among healthy fertile women, which is close to the rate in the general population in our area (28%). The odds ratio for obstetric cholestasis associated with the DD genotype was 2.12 (95% CI, 1.08-4.12) compared with the pooled II and ID genotypes (P = .03). Neither the ID genotype distributions nor the allele frequencies differed significantly between preeclamptic and normotensive pregnancies (P = .36). CONCLUSION: The present data indicate that the DD genotype is a genetic marker associated with an elevated risk of obstetric cholestasis, but this polymorphism of the angiotensin-converting enzyme gene is unlikely to play any significant role in preeclampsia.

Failure in post-transcriptional processing is a possible inactivation mechanism of AP-2alpha in cutaneous melanoma.

The loss of transcription factor AP-2alpha expression has been shown to associate with tumourigenicity of melanoma cell lines and poor prognosis in primary cutaneous melanoma. Altogether these findings suggest that the gene encoding AP-2alpha (TFAP2A) acts as a tumour suppressor in melanoma. To learn more of AP-2alpha's down-regulation mechanisms, we compared the immunohistochemical AP-2alpha protein expression patterns with the corresponding mRNA expression detected by in situ hybridization in 52 primary melanomas. Of the 25 samples with AP-2alpha protein negative areas, 16 (64%) expressed mRNA throughout the consecutive section. Nine specimens (36%) contained equally mRNA- and protein-negative areas, suggesting that the loss of AP-2alpha protein associated with lack of the mRNA transcript. The highly AP-2alpha protein-positive tumours (n = 27) were concordantly mRNA positive in 25 (92.6%) cases. Thirteen primary tumours were further analysed using microsatellite markers D6S470 and D6S263 for loss of heterozygosity (LOH) of a locus harbouring TFAP2A. LOHs or chromosome 6 monosomy were found in four out of five (80%) informative AP-2alpha mRNA- and protein-negative tumour areas, but also within five out of 13 (38%) informative AP-2alpha mRNA-positive tumour areas. This chromosome region is thus suggestive of harbouring a putative tumour suppressor gene of cutaneous melanoma, but this referring specifically to TFAP2A could not be completely verified in this analysis. We conclude that a failure in post-transcriptional processing of AP-2alpha is a possible inactivation mechanism of AP-2alpha in cutaneous melanoma.