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Objectives: The PMCA gene family consists of 4 genes and at least 21 splice variants; among these, the Ca2+ ATPase 4 (PMCA4) gene encodes a plasma membrane protein abundantly expressed in several tissues, including the kidney, heart, and sperm. Knockout of PMCA4 causes infertility due to immotile sperm in mouse models. We therefore investigated variants in this gene for potential association with infertility in groups of Estonian (n = 191) and Latvian (n = 92) men with reduced sperm motility. Methods: All exons, exon- intron boundaries, 5' and 3' untranslated regions, and the promoter region of the PMCA4 gene were analysed by direct sequencing for a group of Estonian infertile men. Genotyp- ing of guanine and adenine alleles of rs147729934 was performed, using a custom-designed TaqMan® probe for a group of Latvian infertile men as well as additional groups from Latvia and several groups of people with proven ethnicity from the Baltic region. Results: Although we did not identify any significant associations between variants in the gene and infertility, our results indicated that in all studied Latvian and Estonian groups the adenine allele of the variant rs147729934 was present at a higher frequency than expected. Analysis of additional samples indicated that the adenine allele of rs147729934 likely originated once in the modern- day Baltic or western Russia area, as the frequency of the minor adenine allele observed in this region is remarkably higher than that in the general European population. Conclusions: Our results revealed no significant difference in frequencies of genetic variants in PMCA4 gene between men with normal and those with reduced sperm motility. The adenine allele of the variant rs147729934 is potentially an informative tool for future population studies concerning ancient Baltic and Finno-Ugric history. [ABSTRACT FROM AUTHOR]

Alcohol metabolism causes cellular damage by changing the redox status of cells. In this study, we investigated the relationship between genetic markers in genes coding for enzymes involved in cellular redox stabilization and their potential role in the clinical outcome of acute alcohol-induced hepatitis. Study subjects comprised 60 patients with acute alcohol-induced hepatitis. The control group consisted of 122 healthy non-related individuals. Eight genetic markers of the genes UGT1A1, GSTA1, GSTP1, NAT2, GSTT1 and GSTM1 were genotyped. GSTT1 null genotype was identified as a risk allele for alcohol-toxic hepatitis progression (OR 2.146, P=0.013). It was also found to correlate negatively with the level of prothrombin (β= −11.05, P=0.037) and positively with hyaluronic acid (β=170.4, P=0.014). NAT2 gene alleles rs1799929 and rs1799930 showed opposing associations with the activity of the biochemical markers γ-glutamyltransferase and alkaline phosphatase; rs1799929 was negatively correlated with γ-glutamyltransferase (β=−261.3, P=0.018) and alkaline phosphatase (β= −270.5, P=0.032), whereas rs1799930 was positively correlated with Γ-glutamyltransferase (β=325.8, P=0.011) and alkaline phosphatase (β=374.8, P=0.011). Enzymes of the glutathione S-transferase family and NAT2 enzyme play an important role in the detoxification process in the liver and demonstrate an impact on the clinical outcome of acute alcohol-induced hepatitis. [ABSTRACT FROM AUTHOR]

Background : High level of homocysteine (Hcy) is risk factor of schizophrenia and mood disorders. Aim: The aim was to detect a serum level of Hcy, examine the associations between the level of Hcy, methylenetetrahydrofolate reductase ( MTHFR) gene C677T polymorphism and clinical properties for patients with schizophrenia, mood disorders and in a control group. Material and methods: There were 88 patients with schizophrenia, 28 with affective disorders and 94 from the control group. The Hamilton Anxiety Scale (HAM-A) was performed to study anxiety, the Hamilton Depression Scale (HAM-D) to study depression and the Brief Psychiatric Rating Scale (BPRS) to study severity of schizophrenia. The level of Hcy was stated by isocratic high-performance liquid chromatography (HPLC) system with fluorometric detection. DNA isolation from venous blood was performed by the phenol-chloroform method. Results: The levels of B12 vitamin and folic acid were within normal limits for all the patients. The average level of Hcy was 11.94 ± 5.6 μmol/l for patients with schizophrenia and 11.65 ± 3.3 μmol/l for patients with affective disorders, vs. 6.80 ± 2.93 μmol/l in a control group. The highest level of Hcy has been observed in patients with an episodic-recurrent course of schizophrenia, paranoid schizophrenia-continuous, particularly in patients with CT genotype ( r = − 0.58; P < 0.01). In the given diagnostic groups, the highest level of anxiety was observed. Conclusions: The level of Hcy is higher in the blood of a heterozygotic person who becomes ill with schizophrenia, and the process of the illness is more serious and with more typical affective disorders. [ABSTRACT FROM AUTHOR]

Several genetic loci in chromosomes 11 and 15 have recently been associated with non-syndromic autism spectrum disorder (ASD) in populations from North America and Europe. The aim of the present study was to investigate whether such an association exists in a Latvian population. Ninety-five patients with ASD in the age range 3-20 years (mean age 8 years, SD 3.18) participated in the study. The control group consisted of 161 healthy, non-related individuals without ASD randomly selected from the Latvian Genome Database. Four single nucleotide polymorphisms (SNPs) - rs11212733, SNP rs1394119, rs2421826, rs1454985 - were genotyped by the TaqMan method. Allele frequency differences between ASD patients and control subjects were compared for each SNP using a standard chi-square test with Bonferroni correction. The level of statistical significance was set at 0.05 for nominal association. Only the genetic marker rs11212733, localised on the long arm of chromosome 11 in locus 22.3, was found to be strongly associated with the ASD patient group (χ2 6.982, Padjusted 0.033, odds ratio 1.625). Our data demonstrating a significant relationship between the SNP rs11212733 and the development of ASD in a Latvian population suggest that it is not a population-specific relationship. Thus, future studies focusing on the DDX10 gene and related genetic loci are needed. [ABSTRACT FROM AUTHOR]

Background: Nonsyndromic cleft lip with or without cleft palate (CL/P) is a common complex birth defect caused by the interaction between multiple genes and environmental factors., Methods: Five hundred and eighty-seven single nucleotide polymorphisms in 40 candidate genes related to orofacial clefting were tested for association with CL/P in a clefting sample composed of 300 patients and 606 controls from Estonian, Latvian, and Lithuanian populations., Results: In case-control comparisons, the minor alleles of FGF1 rs34010 (p = 4.56 × 10(-4) ), WNT9B rs4968282 (p = 0.0013), and FOXE1 rs7860144 (p = 0.0021) were associated with a decreased risk of CL/P. Multiple haplotypes in FGF1, FOXE1, and TIMP2 and haplotypes in WNT9B, PVRL2, and LHX8 were associated with CL/P. The strongest association was found for protective haplotype rs250092/rs34010 GT in the FGF1 gene (p = 5.01 × 10(-4) ). The strongest epistatic interaction was observed between the COL2A1 and WNT3 genes., Conclusions: Our results provide for the first time evidence implicating FGF1 in the occurrence of CL/P, and support TIMP2 and WNT9B as novel loci predisposing to CL/P. We have also replicated recently reported significant associations between variants in or near FOXE1 and CL/P. It is likely that variation in FOXE1, TIMP2, and the FGF and Wnt signaling pathway genes confers susceptibility to nonsyndromic CL/P in Northeastern European populations., (Copyright © 2011 Wiley-Liss, Inc.)