Exome Sequencing Identifies Susceptibility Loci for Sarcoidosis Prognosis

Many sarcoidosis-associating immunological genes have been shown to be shared between other immune-mediated diseases. In Finnish sarcoidosis patients, good prognosis subjects more commonly have HLA-DRB1*03:01 and/or HLA-DRB1*04:01-DPB1*04:01 haplotype, but no marker for persistent disease have been found. The objective was to further pinpoint genetic differences between prognosis subgroups in relation to the HLA markers. Whole-exome sequencing was conducted for 72 patients selected based on disease activity (resolved disease, n = 36; persistent disease, n = 36). Both groups were further divided by the HLA markers (one/both markers, n = 18; neither of the markers, n = 18). The Finnish exome data from the Genome Aggregation Database was used as a control population in the WES sample. Statistical analyses included single-variant analysis for common variants and gene level analysis for rare variants. We attempted to replicate associated variants in 181 Finnish sarcoidosis patients and 150 controls. An association was found in chromosome 1p36.21 (AADACL3 and C1orf158), which has recently been associated with sarcoidosis in another WES study. In our study, variations in these genes were associated with resolved disease (AADACL3, p = 0.0001 and p = 0.0003; C1orf158, p = 7.03E-05). Another interesting chromosomal region also peaked, Leucocyte Receptor Complex in 19q13.42, but the association diminished in the replication sample. In conclusion, this WES study supports the previously found association in the region 1p36.21. Furthermore, a novel to sarcoidosis region was found, but additional studies are warranted to verify this association.Peer reviewe

High relative amount of nodular calcification in femoral plaques is associated with milder lower extremity arterial disease.

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Complement activation and regulation in preeclamptic placenta

Lokki Anna Inkeri1,2,3; Heikkinen-Eloranta Jenni1,4; Jarva Hanna2,3,5; Saisto Terhi4; Lokki Marja-Liisa6; Laivuori Hannele1,4; and Meri Seppo2,3,5.Peer reviewe

Soluble HLA-DR serum levels are associated with smoking but not with acute coronary syndrome

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Copy Number Analysis of Complement C4A, C4B and C4A Silencing Mutation by Real-Time Quantitative Polymerase Chain Reaction

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Diversity of Extended HLA-DRB1 Haplotypes in the Finnish Population

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Genetic support for the causal role of insulin in coronary heart disease

Epidemiological studies have identified several traits associated with CHD, but few of these have been shown to be causal risk factors and thus suitable targets for treatment. Our aim was to evaluate the causal role of a large set of known CHD risk factors using single-nucleotide polymorphisms (SNPs) as instrumental variables.Peer reviewe

Complement C4 Deficiency - A Plausible Risk Factor for Non-Tuberculous Mycobacteria (NTM) Infection in Apparently Immunocompetent Patients

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Recurrent Lymphocytic Meningitis Positive for Herpes Simplex Virus Type 2

We found the prevalence of recurrent lymphocytic meningitis associated with herpes simplex virus type 2 (HSV-2) was 2.2/100,000 population in Finland during 1996–2006, higher than previous estimates. PCR was most sensitive in detecting HSV-2 DNA from cerebrospinal fluid if the sample was taken 2–5 days after symptom onset