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C Sikström

Publications and source records attributed to C Sikström.

At least 19 recordsLinked to original sources
PubMed1999

Interaction between haemochromatosis and transferrin receptor genes in different neoplastic disorders.

A number of genes are involved in iron metabolism, including the transferrin receptor (TFR) and haemochromatosis (HFE) genes. In previous investigations an increased risk for neoplastic disease has been observed in individuals homo- and heterozygous for hereditary haemochromatosis. The HFE wild-type gene product complexes with the transferrin receptor (TF) and two different HFE mutations (Cys282Tyr and His63Asp) have been found to increase the affinity of TFR for TF and increase cellular iron uptake. In a recent study we found no associations for HFE and TFR separately, but an interaction between HFE and TFR genotypes in multiple myeloma. Individuals carrying the HFE Tyr282 allele (homo- and heterozygotes) in combination with homozygosity for the TFR Ser142 allele had an increased risk. In the present study the same association was found in breast and colorectal cancer. The odds ratio for all three neoplasms combined was 2.0 (95% CI 1.0-3.8). The risk for neoplastic disease was further increased (OR 7.7, 95% CI = 1.0-59.9) when the analysis was restricted to HFE Tyr homozygotes and compound heterozygotes in combination with TFR Ser homozygosity. Thus, an interaction between HFE and TFR alleles may increase the risk for different neoplastic disorders.

Alleles↗
PubMed1999

Protective effect of transferrin C3 in lung cancer?

In a previous study of lung cancer patients and controls from the Stockholm area in central Sweden, we found a significantly decreased frequency of the transferrin (TF) variant C3 in small cell and squamous epithelial lung cancer but not in adenocarcinoma, suggesting a protective effect of TF C3 in small cell and squamous lung cancer. In an attempt to replicate this association we studied TF types in lung cancer patients and controls from two additional Swedish subpopulations, viz. northern Sweden and southwestern Sweden. We were able to confirm the significantly decreased frequency of TF C3, especially in small cell lung cancer, in northern Sweden but not in southwestern Sweden. Thus the eventual protective effect of TF C3 in small cell lung cancer is an open question. We hypothesize that the association between TF C alleles and lung cancer may be secondary and dependent on linkage disequilibrium with allelic variants of newly discovered tumor-associated genes known to map to the same position (3q21) as TF, e.g. NCK and H-RYK.

Adenocarcinoma↗
PubMed1999

alpha1-antitrypsin (PI) alleles as markers of Westeuropean influence in the Baltic Sea region.

The distribution of alpha1-antitrypsin (PI) alleles was studied in an attempt to elucidate migrations and admixture between populations in the Baltic Sea region. The frequency of the PI Z allele, a typically Northwesteuropean marker gene, showed a highly significant regional variation in the Baltic Sea region. The highest frequency (4.5%) was found in the western part of Latvia (Courland). The PI S allele, another marker of Westeuropean influence, also showed an increased frequency in the Courland population. These results indicate that among the populations east of the Baltic Sea the Curonian population has the most pronounced Westeuropean influence. Archaeological data have shown that from the 7th century and for several hundreds of years Courland received immigrations from mainland Sweden and the island of Gotland. We speculate that the increased frequencies of the PI Z alleles and S alleles in Courland may have been caused by these migrations.

Alleles↗
PubMed1998

Transferrin C2, metal binding and Alzheimer's disease.

Significant associations between the transferrin (TF) variant C2 and a number of disorders suspected to be caused by oxygen free radicals have been reported. Thus an increased frequency of the TFC2 variant has been found in patients with Alzheimer's disease (AD), and it has been hypothesized that AD is caused by free radical damage due to defective binding of iron and aluminium by TFC2. In a study of 64 patients with AD from northern Sweden we were able to confirm the association between TFC2 and AD, but there were no significant differences between TFC2 and other TF variants with respect to the binding of iron and aluminium.

Aluminum↗
PubMed1998

DNA polymorphisms and haplotypes in the human transferrin gene.

Although a large number of human serum transferrin (TF) variants have been described, only one RFLP (AvaI) has so far been found. Here we report three new RFLPs (MvaI in intron 5 and exon 7, BbvI in exon 7) and correlations between RFLPs and between RFLPs and serum TF types. There were strong, but not always complete, disequilibria between RFLP and serum protein alleles. Thus, the most common serum TF variant, C1, was heterogeneous and could be subdivided into two common haplotypes, whereas the C2, C3, and DCHI variants were completely or almost completely (C2) homogeneous. There was a total genotypic agreement between the BbvI polymorphism and the presence/absence of the TF C3 variant, and the mutation that creates the BhvI site was found to lead to a G258S amino acid substitution.

DNA↗
PubMed1996

Genetic markers associated with high versus low performance on episodic memory tasks.

Associations were studied between six serum protein polymorphisms (C3, BF, HP, ORM, TF, and GC) and high versus low scoring on episodic memory tasks in an attempt to identify QTL (quantitative trait loci) contributing to the heritability of this quantitative trait. Since a highly significant sex difference (p = .00002) was found with respect to the distribution of high and low scoring, with men showing a poorer performance, associations were studied separately for males and females. In females significant differences (p < .05) between the high and the low groups were found in four of six marker systems (C3, HP, TF, and CG), whereas in males a significant difference was found only in the HP system. Significant differences from population frequencies were also found more frequently in females than in males. The strongest marker associations were found with complement C3 and the acute-phase reactant HP, which suggests that immune response factors may be of importance in preserving episodic memory function. The overall results appear to indicate that episodic memory is a multifactorial and heritable quantitative trait where sex is an important determinant.

Adult↗
PubMed1996

Transferrin C3 offers protection against smoking-associated lung cancer?

In previous investigations increased body iron stores and transferrin (TF) variants have been found to be associated with adverse health effects, including cancer. In this investigation transferrin C (TF C) subtypes were studied in lung cancer patients and controls from the Stockholm area in central Sweden. There was a significant difference between patients and controls with respect to the distribution of TF C alleles and genotypes, which was mainly due to a low frequency of the TF C3 allele among the patients (P = 3 x 10(-6). However, in adenocarcinoma the frequency of TF C3 types was almost identical to that among the controls, whereas in the smoking-related (squamous and small cell) tumor types the TF C3 frequency was remarkably low (OR = 0.03, 95% CI = 0.00-0.22). Thus individuals with the TF C3 variant appear to enjoy an almost complete protection against smoking-related lung cancer. The frequency of individuals carrying the protective TF C3 variant is approximately 17% in central Sweden and 25% in Finland, which has the highest TF C3 frequency found so far. The mechanism behind the observed association, which appears to be independent of iron binding and body iron stores, remains to be elucidated.

Adenocarcinoma↗
PubMed1995

Localization of the gene for congenital dyserythropoietic anemia type III, CDAN3, to chromosome 15q21-q25.

Congenital dyserythropoietic anemia, type III (CDA III) is a rare autosomal dominant disorder characterized by macrocytic anemia, bone marrow erythroid hyperplasia and giant multinucleate erythroblasts. We have genetically characterized a large Swedish family in which the concurrence of CDA III and myeloma or benign monoclonal gammopathy is significantly higher than expected and have found that the causative genetic defect for CDA III maps to an 11 cM interval within 15q21-q25.

Anemia, Dyserythropoietic, Congenital↗
PubMed1995

Orosomucoid and haptoglobin types in patients with sarcoidosis.

Association with HLA and complement factors has been reported in sarcoidosis, and the results of previous studies suggest a multifactorial and immunogenetic etiology of the disease. We have studied two genetic acute-phase reactant systems, orosomucoid (ORM) and haptoglobin (HP), in 226 patients with sarcoidosis and population controls from northern Sweden. Significant allele and phenotype differences between patients and controls were found in both systems. The ORM1 phenotype showed a significant increase in sarcoidosis (RR = 1.34, p = 0.036), which was more pronounced among patients with low (< 1,500 nkat/l) angiotensin-converting enzyme levels (RR = 1.83, p = 0.00065) and hypercalcemia (RR = 3.69, p = 0.0023). The HP1 type was significantly increased among the sarcoidosis patients (RR = 1.57, p = 0.013). The results suggest that the ORM1 1 and HP1 types may be contributory determinants in the multifactorial etiology of sarcoidosis.

Female↗
PubMed1992

DNA polymorphism of alkaline phosphatase isozyme genes: linkage disequilibria between placental and germ-cell alkaline phosphatase alleles.

The use of human placental alkaline phosphatase (PLAP) cDNA as a probe allows the detection and identification of restriction DNA fragments derived from three homologous genes, i.e., intestinal alkaline phosphatase (AP), germ-cell AP (GCAP), and PLAP. In previous RFLP studies we have reported linkage disequilibria between an RsaI and two PstI (a and b) polymorphic restriction sites and electrophoretic types of PLAP. In this report we present evidence that, in spite of the strong correlation with PLAP types, PstI(b) is an RFLP of GCAP. The data indicate close linkage between the PLAP and GCAP loci.

Alkaline Phosphatase↗
PubMed1991

A new PstI restriction fragment length polymorphism (RFLP) of placental alkaline phosphatase. RFLP haplotypes and correlation with electrophoretic types.

A new PstI restriction fragment length polymorphism (RFLP) of placental alkaline phosphatase (PLAP) was discovered in a study of a Finnish population sample and designated PstI(b)1 or Pst(b)2 depending on the presence or absence of the cleavage site. The frequency of the PstI(b)2 allele was 0.24. This allele showed a positive (p = 3 x 10(-6) association with the electrophoretic allele 2(F) and a negative association (2 x 10(-7) with the electrophoretic allele 1(S). The previously described PstI RFLP [PstI(a)] was also found to be associated with electrophoretic types; the PstI(a)1 allele (presence of site) was associated with the electrophoretic type 2 (p = 0.023). Haplotype frequencies and disequilibria were calculated between PstI(a), PstI(b) and RsaI RFLPs. A complete disequilibrium (p = 1 x 10(-6) was found between PstI(a) and RsaI, whereas there was no significant disequilibrium between PstI(b) and RsaI. There was no strict correlation between the distances between the RFLP loci and the degree of linkage disequilibrium. The allele controlling the electrophoretic variant PLAP 18 (D) was found in polymorphic frequency (0.024) in the Finnish population.

Alkaline Phosphatase↗
PubMed1991

GC serum groups and otosclerosis.

Five genetic serum protein marker systems (HP, TF, GC, BF and PI) were studied in patients with otosclerosis and in controls. The distributions of GC phenotypes and alleles showed significant differences between patients and controls with an excess of the IF-allele and the IF-variant among the patients.

Alleles↗
PubMed1990

Transferrin C subtypes and ethnic heterogeneity in Sweden.

Transferrin (TF) C subtypes were studied in Swedish Lapps (Saami) and in Swedes from northern, central and southern Sweden, and the allele frequencies were compared with those in other European populations. The Swedish Lapps were found to have the lowest frequency of the TF*C3 allele (1-2%) so far observed in Europe. Most European populations have TF*C3 allele frequencies between 5 and 7%. Finns differ by having high TF*C3 frequencies (13-14%). The relatively high TF*C3 frequencies found in northeastern Sweden (13%) and in central Sweden (9%) are most likely due to eastern influence. Unlike other genetic markers of eastern influence (e.g. TF*DCHI), which are of Asiatic Mongoloid origin, TF*C3 appears to originate from Finno-Ugric populations.

Alleles↗
PubMed1989

Correlation between RsaI restriction fragment length polymorphism and electrophoretic types of human placental alkaline phosphatase.

Restriction fragment length polymorphism (RFLP) of human alkaline phosphatases was studied in a population sample from northern Sweden using a placental alkaline phosphatase (PLAP) cDNA probe. After digestion of human genomic DNA with RsaI the Southern blots showed DNA fragments most probably derived from three genes: PLAP, germ cell alkaline phosphatase (PLAP-like) and intestinal alkaline phosphatase. In agreement with a previous study, a two-allele polymorphism was found in PLAP with bands at 1.6 kilobases (A1) and 1.8 kilobases (A2). The gene frequencies of A1 and A2 were 0.46 and 0.54, respectively. There was a significant correlation between the RsaI RFLPs and electrophoretic types of PLAP; RSAI A2 showed an association with the ALP2p allele of PLAP.

Alkaline Phosphatase↗
PubMed1988

Population studies in northern Sweden. XV. Transferrin C subtypes.

The frequencies of transferrin C (TF C) subtypes were studied in 315 Finns, 222 Swedish Lapps and in 4,157 conscripts and blood donors from the counties of Norrbotten and Västerbotten in northern Sweden. The Swedish individuals were distributed according to place of birth into 23 subpopulations or regions. A significant heterogeneity between the 23 regions was observed for the TF C1, C2 and C3 genes and for rare genes. Clines were found for the TF C1 and C3 genes and for rare transferrin genes in northern Sweden. The frequencies of the C1 and C3 genes were increasing in the southwestern and northeastern direction, respectively, and the frequency of the rare transferrin genes was increasing in the northern direction. The geographical picture of the C3 gene and of rare transferrin genes could be interpreted in terms of Finnish influence. The frequency of the TF C3 gene in Finland and northern Sweden (14 and 15%) is the highest so far reported in the world. The overall picture of geographical variations of the C1 and C2 genes were not explainable in terms of ethnic influence and may be caused by random differentiation and/or selective forces.

Finland↗
PubMed1985

Transferrin C subtypes and occupational photodermatosis of the face.

In a factory in northern Sweden where 120 workers were uniformly exposed to photoactive substances 73 developed occupational facial eczema while 47 showed no reaction. The workers were examined with respect to 16 genetic marker systems: HLA, blood groups (ABO, Rh, MNSs, P, K, Le and Fy) and serum groups (Hp, Tf, Gc, Pi, Bf, C3, C4 and C6). Between reactors and nonreactors the following differences were found: (1) a significant decrease (p less than 0.05) of HLA A11 among the reactors; (2) a significant increase (p less than 0.05) of the C3 FS type among the reactors; (3) a highly significant increase (p less than 0.001) of the transferrin C2 gene and of the C2 variant among the reactors. The association with Tf C2 remained significant also after correction for number of significance tests. Since transferrin (iron) is known to catalyze the formation of hydroxyl radicals we hypothesize that the Tf C2 variant is more efficient in promoting radical formation and thereby cell damage. Other results supporting the notion that transferrin C2 may be associated with an increased susceptibility to toxic damage are discussed.

Blood Group Antigens↗