Bioinformatic Analysis of Evolutional Conservatism and Functional Significance of Microsatellite Alleles of Human 14Q13.2 Region Associated with Type 2 Diabetes Mellitus
The paper deals with bioinformatic and statistical analysis of the possible functional significance of the previously shown association of several microsatellite alleles in intron 6 of the human proteasome core particle PSMA6 gene (HSMS006) and four other microsatellites localised upstream in human chromosome 14q13.2 (HSMS801, HSMS702, HSMS701, HSMS602) with type 2 diabetes mellitus in Latvia and Botnia, Finland. Genotype analysis revealed that (CAA)8/(CAA)8 homozygotes of the HSMS602 marker were never found in Type 2 diabetes patients, although 6.56% of the individuals from the control groups were the (CAA)8/(CAA)8 homozygotes. For the HSMS801 marker the (AC)21/(AC)23 genotype was never found in the case group and in the control group it was detected with a frequency 4.40%; these differences were statistically significant (P < 0.05). In contrast to the Latvian population, the distribution of genotype frequencies in cases and controls taken from the Botnian dataset was almost similar. Haplotype analysis showed that in the Latvian population besides haplotypes including alleles differently represented in case and control groups, a combination of some alleles almost equally represented in both groups formed combinations that were more characteristic of either the case group or the control group. This indicates probable independent functional significance of these haplotypes that warrants further investigation. In the Botnian population, more allele combinations were observed, and the distribution of haplotypes in case and control groups differed from that observed in Latvia. The observed haplotype distributions might reflect differences between the studied populations: a homogenous and isolated Botnian vis-à-vis a mixed Latvian population. Linkage disequilibrium (LD) analysis of data on the Latvian population revealed nine of ten two-allele combinations manifesting a high LD. HSMS006 and HSMS602 combination had a low LD; among the analysed markers these were situated at the largest distance from one another. Data on the Botnian population showed that haplotypes in eight of ten combinations had a high LD, including the HSMS006 and HSMS602 combinations. It appears that the two populations differ also in linkage disequilibrium of two-loci haplotypes. Theoretical analysis of a potential functional role of the polymorphisms indicated the significance of the microsatellite length of HSMS602 and HSMS006 for the formation of DNA hairpins. The whole genomic region appears to be conservative in mammals.
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.
The most common autoimmune disorders with clinically opposite manifestations are hypothyroidism in Hashimoto’s thyroiditis and hyperthyroidism in Graves’ disease. The healthcare burden of thyroid disease is substantial, resulting in substantial health care costs. The aim of the present analysis is to assess the use of thyroid medications in Latvia from 2011 to 2014 by age and gender. Our study used reimbursed medication prescriptions data, collected by the National Health Service of Latvia. The main indicator was the number of prevalent users of thyroid medications each year from 2011 to 2014, stratified by age and gender. From 2011 to 2014, the number of thyroxine users per 100 000 revealed a statistically significant increase in all age and gender groups, except in 0- to 9-year-old girls. The number of Thiamazole users among men increased in the age group from 40 to 89 years and in women age groups above 49 years. Increasing sales of both thyroid hormones and antithyroid medications are also observed in Estonia and Lithuania, indicating that growing thyroid morbidity is an issue in the whole region. The substantial increase in number of patients highlights the necessity for national guidelines on the use of thyroid function tests and standards of medical care.
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.
Relation of Endothelial Dysfunction and Adipokines Levels to Insulin Resistance in Metabolic Syndrome Patients
Obese metabolic syndrome (MS) patients were categorised into three groups: 44 with type 2 diabetes mellitus (T2DM)(D); 20 with T2DM and coronary artery disease (CAD) (DC), and 26 with MS alone (M). Eighteen healthy subjects were selected as controls (C). Insulin resistance (IR) was assessed by HOMA-IR. Adiponectin, tumour necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), monocyte chemoattractant protein-1 (MCP-1), and interleukin-8 (IL-8) concentrations were measured by xMAP technology. Endothelin-1 (ET-1) was determined by ELISA. We used laser Doppler imaging for evaluating cutaneous endothelium-dependent vasodilatation in the hand. D and DC groups had significantly elevated IR compared with M or C group (P < 0.01). TNF-α, IL-6, IL-8, MCP-1 and ET-1 levels in DC were significantly elevated compared with other groups (P < 0.001). IL-6, IL-8, MCP-1 and ET-1 in D group were higher than those in C group (P < 0.05). TNF-α, IL-6, IL-8, MCP-1 and ET-1 concentrations were correlated with HOMA-IR indexes and adiponectin levels. All patients had lower adiponectin concentrations than controls (P < 0.001), but there were no differences between the patient groups. Only D and DC groups demonstrated a significant and similar decrease in LDI-Ach marker compared to C group (P < 0.001). LDI-Ach values were significantly correlated with HOMA-IR indexes and adiponectin levels (P < 0.001). Our findings show that obese MS patients have significantly increased HOMA-IR, TNF-α, IL-6, MCP-1 and IL-8 levels, decreased adiponectin concentration, and endothelial dysfunction, but the presence of T2DM and CAD in these patients is associated with more pronounced endothelial dysfunction and increased production of inflammatory cytokines and chemokines.
In the absence of a mandatory salt iodisation programme, two nationwide cross-sectional cluster surveys revealed persisting iodine deficiency among Latvian schoolchildren during the spring season and a noteworthy iodine deficiency in pregnant women in Latvia; these deficiencies warrant intervention. The consequences of mild-to-moderate iodine deficiency during pregnancy and lactation can adversely affect foetal brain development. Data from a Latvian population survey revealed the consumption of approximately 100 μg of iodine per day through foods and iodised salt. Therefore, strategies to increase the consumption of iodine-containing products should be implemented, particularly for children. In addition, to meet the increased iodine requirement during pregnancy, pregnant women should take daily supplements containing 150 μg iodine from the earliest time possible. All women of childbearing age should be advised to increase their dietary iodine intake by using iodised table salt and iodine-rich products: seafood, milk and milk products. For women with pre-existing thyroid pathologies, the medical decision should be considered on a case-by-case basis. Urinary iodine concentration monitoring among schoolchildren and pregnant women and neonatal thyrotropin registry analysis every five years would be an appropriate strategy for maintaining iodine intake within the interval that prevents iodine deficiency disorders.