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  • Author: Jānis Kloviņš x
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Interleukin 18 gene promoter polymorphisms in Latvian patients with rheumatoid arthritis

Interleukin 18 (IL-18) is a proinflammatory cytokine involved in the pathogenesis of rheumatoid arthritis (RA). There are controversial reports suggesting that IL-18 promoter polymorphisms may be an independent marker of RA susceptibility. The aim of the present study was to determine whether polymorphisms of the IL-18 gene promoter in positions -607 (rs 1946519) and -656 (rs 1946518) are associated with RA, and its characteristics in the Latvian population. We examined 105 patients with RA diagnosed according to the criteria of the American College of Rheumatology. DNA and phenotypic data from a healthy control population was obtained from Genome Database of Latvian Population. Genotypes were obtained by direct sequencing. Single-nucleotide polymorphisms (SNPs) were studied and frequencies of alleles and genotypes were compared between patients and controls. A P value less than 0.05 was accepted as statistically significant. There were no significant differences in the distribution of alleles and genotypes between RA patients and the control group. The frequencies of IL-18-607C/A and -656G/T genotypes differed between patients and the control group in women (P = 0.084 and 0.097). Heterozygous genotypes -607CA and -656GT occurred more frequently in the RA group than in the control (P = 0.046, P = 0.060), and this difference was also significant for the only women groups (P = 0.041,P = 0.054). The heterozygous states -607CA and -656GT of IL-18 gene affect susceptibility to RA. On the basis of investigated IL-18 polymorphisms, female patients with RA seem to represent a separate disease subgroup.

Glucose Metabolism Disorders and Risk Factors of Type 2 Diabetes in 45-74-Years-old Population in Rīga, Latvia

The aims of this study were to investigate the current prevalence of abnormal glucose tolerance (AGT), compare the risk factor profile between persons with and without AGT among 45-74 years-old Latvian men and women, and to validate the Finnish diabetes risk score (FINDRISC) questionnaire in detecting AGT in the middle-aged Latvian population. A cross-sectional survey among the 45-74-years old population randomly selected from the registers of general practitioners in Rīga, Latvia was carried out between April 2008 and March 2009. The survey consisted of a questionnaire, measurements such as height, weight, waist circumference, and blood pressure as well as blood oral glucose tolerance test (OGTT), cholesterol and its fractions. Prevalence of obesity, central obesity and physical inactivity were high in the Latvian population. Women with AGT had a worse risk factor profile for T2D and cardiovascular diseases compared to those with normal glucose tolerance. No differences were found in the risk factor profile between men with and without AGT. A high proportion of men and women with more than 11 FINDRISC points had undetected AGT. The FINDRISC questionnaire can be used in clinical practice to detect persons with AGT in the Latvian population.

Abstract

This article presents a review on population genetics of Latvians, which alongside Lithuanians are the two extant Baltic speaking populations. The article provides a description of genome-wide single nucleotide polymorphism (SNP) data and contains a comparative analysis of the results of studies performed on classical autosomal genetic markers, mitochondrial DNA (mtDNA) and the non-recombining part of the Y chromosome (NRY), with data on neighbouring populations. The study also covers data of recently performed ancient DNA (aDNA) studies carried out on samples from the territory of today’s Latvia. The results of population genetic studies have shown a mixture of eastern and western genetic traits in present-day Latvians with only small differences between Latvian subpopulations. Studies of the Baltic “tribal gene” LWb, as well as the gene’s SERPINA1 allele PIZ have indicated the presence of a considerable Baltic admixture in the neighbouring Finno-Ugric and Slavic populations. Although mtDNA analyses have shown that Latvians genetically in general belong to the same common gene pool as most of the Europeans, the Y-chromosomal lineage composition suggests that they are most similar to Northern and Eastern European populations of Lithuanians, Estonians, and Eastern-Slavic populations, which are ethnogenetically closest to them. The analysis of aDNA from the Early and Middle Neolithic did not present any genomic evidence of gene-flow from Central European farmers or any mitochondrial or Y-chromosomal haplogroups that are typical for them in the hunter-gatherers from the territory of today’s Latvia and Lithuania.

Analysis of Polymorphisms at the Adiponectin Gene Locus in Association with Type 2 Diabetes, Body Mass Index and Cardiovascular Traits in Latvian Population

Despite the number of recently conducted studies seeking to determine the association between genetic variants of adiponectin gene and susceptibility to type 2 diabetes (T2D) and increased body mass index (BMI), the results obtained are often inconsistent. To determine the impact of common polymorphisms in promoter and coding regions of adiponectin gene on these conditions in Latvian population, we selected ten SNPs (rs2241767, rs1501299, rs3777261, rs16861210, rs2241766, rs822396, rs182052, rs17300539, rs16861194, rs266729) based on haploblock structure and previously reported association studies. The selected SNPs were screened in a study group of 835 participants from the Genome Data Base of Latvian Population and mainly consisted of patients with T2D and coronary heart disease. None of the individual polymorphisms were significantly associated with T2D status or BMI when analysed using logistic or linear regression and adjusted for gender, age and other significant covariates. Frequency of rs2241766 T allele homozygotes however was significantly increased in T2D patients compared to controls (uncorrected P = 0.007). When analysed with other traits, the rs182052 G allele was found to be less frequent in patients suffering from myocardial infarction (P = 0.02; OR = 0.76, CI95% [0.61-0.92]) compared to others. Haplotype analysis revealed significant association of one haplotype with atrial fibrillation (uncorrected P = 0.01). In summary, we conclude that SNPs in adiponectin gene are unlikely to represent the risk for T2D, but may be involved in pathogenesis of CHD in the Latvian population.

Abstract

Familial hypercholesterolemia (FH) is one of the most common single gene disorders, which is mostly inherited as an autosomal dominant trait. The physical signs of FH are elevated low density lipoprotein cholesterol (LDL-C), elevated total cholesterol (TC) levels and tendon xantomas. Identification and early treatment of affected individuals is desirable and in lack of physical symptoms DNA-based diagnosis provides confirmation of diagnosis and enables early patient management. The majority of FH cases are caused by mutations in four genes (APOB, LADLR, PCSK9, and LDLRAP1). There are commercial kits available for testing of the 20 most common FH causing mutations, but the spectrum of disease-causing mutations is quite diverse in various populations and these tests cover only a minority of disease-causing genetic variants. There is therefore a need to determine the full spectrum of mutations in LDLR, APOB, PCSK9, and LDLRAP1 genes in each population. Here we report mutations found in 16 patients with suspected FH in a sample from the Genome Database of the Latvian population enrolled at the Latvian Centre of Cardiology. We used the next generation sequencing approach to determine the full spectrum of mutations in coding regions of LDLR, APOB, PCSK9, and LDLRAP1. In total we found 22 missense mutations, from which only rs5742904 (Arg3527Gln) in APOB gene had been previously described as a FH-causing mutation confirming FH in one patient. Possible FH-causing mutations however, were identified in the majority of patients. The conclusion is that the most commonly employed commercial mutation panel is not sufficient for diagnosis of FH patients and NGS can help to identify FH-causing mutations in the Latvian population.