Analysis of molecular genetic study on the polymorphic C-159T locus of the <Emphasis Type="Italic">CD14</Emphasis> gene in children with increased risk of recurrent episodes of acute obstructive bronchitis

A molecular genetic study of the polymorphic C-159T locus of the CD14 gene has been carried out in 31 children with recurrent episodes of acute obstructive bronchitis as well as in a cohort of 50 randomly sampled subjects forming the control group. As a result of the study, no higher statistically significant frequency of the CC, CT, and TT genotypes has been recorded at the polymorphic C-159T locus of the CD14 gene among children of the main group compared with the control. However, there is a trend towards a more frequent observation of the TT genotype among children with recurrent episodes of acute obstructive bronchitis compared with the control group (32.25 vs. 22.0%).     

Association between <Emphasis Type="Italic">TNF,IL1B,IL6, IL10</Emphasis> and <Emphasis Type="Italic">IFNG</Emphasis> polymorphisms and recurrent miscarriage: a case control study

Background

Approximately half of recurrent miscarriages have unexplained etiology. Recent evidences suggest that cytokines are important determinants in pregnancy maintenance and as such, cytokine gene polymorphisms, which can affect cytokine production and/or functionality, could play a role in the disorder. Thus, we aimed to investigate the association of selected cytokine gene polymorphisms with risk of recurrent miscarriage among Chinese.

Methods

TNF -238G > A, TNF -308G > A, IL1B -511 T > C, IL1B 3954C > T, IL6 -174G > C, IL6 -634C > G, IL10 -1082A > G and IFNG 874A > T polymorphisms were genotyped on 775 women with idiopathic recurrent miscarriage and 805 healthy parous control women. Logistic regression analysis was performed to determine the odds ratios (ORs) of the association between the polymorphisms and recurrent miscarriage risk.

Results

Among the eight polymorphisms studied, only the IL1B -511 T > C and IL6 -634C > G polymorphisms showed statistically significant associations with recurrent miscarriage risk. For the former, a significantly increased risk of recurrent miscarriage was observed for the mutant (CC) genotype (OR: 1.377; 95% CI: 1.039–1.824; P?=?0.026). However, for the IL6 -634C?>?G polymorphism, a decreased recurrent miscarriage risk was observed for the heterozygous (CG) genotype (OR: 0.614; 95% CI: 0.493–0.765; P < 0.001) and the mutant (GG) genotype (OR: 0.414; 95% CI: 0.251–0.684; P?=?0.001).

Conclusions

The IL1B -511 T > C polymorphism may serve as important risk factor for recurrent miscarriage while the IL6 -634C > G polymorphism may protect against the risk of recurrent miscarriage.

     

Polymorphic markers <Emphasis Type="Italic">Val762Ala</Emphasis> and <Emphasis Type="Italic">Leu54Phe</Emphasis> of the <Emphasis Type="Italic">ADPRT1</Emphasis> gene associated with chronic glomerulonephritis in Russian patients from Moscow

A comparative analysis of allele and genotype distribution of polymorphic markers Val762Ala and Leu54Phe of ADPRT1 gene encoding poly(ADP-ribose)polymerase1 has been performed in chronic glomerulonephritis patients compared to normal controls. This has shown a significant difference in the ADPRT1 gene polymorphic marker Val762Ala allele and genotype frequency distribution between chronic glomerulonephritis patients and healthy controls (according to Fisher’s exact test). At the same time the allele and genotype frequency for a polymorphic marker Leu54Phe distribution did not show significant difference between these groups. Therefore, we have concluded that the ADPRT1 gene polymorphic marker Val762Ala is associated with the development of chronic glomerulonephritis in Russian patients of the Moscow region.     

Association of variable <Emphasis Type="Italic">rs1801282</Emphasis> locus of <Emphasis Type="Italic">PPARG2</Emphasis> gene with diabetic nephropathy

The association of the variable rs1801282 locus of the PPARG2 gene (peroxisome proliferator-activated receptor gamma) with type 2 diabetes mellitus and its complications was analyzed in inhabitants of the Republic of Bashkortostan. The genotype frequencies of the variable rs1801282 locus of the PPARG2 gene did not significantly differ in groups of healthy persons and patients with type 2 diabetes in all three considered inheritance models (codominant, dominant, and recessive). At the same time, it was demonstrated that the risk of one of the diabetic complications, i.e., diabetic nephropathy, was associated with the variable rs1801282 locus of the PPARG2 gene. Diabetic nephropathy was more common in patients with the C/C genotype (62.7%) compared to the C/G and G/G genotypes (37.5%), P = 0.036. The G allele is protective in regard to diabetic nephropathy (OR = 0.36) in patients with type 2 diabetes mellitus.     

The analysis of association between type 2 diabetes and polymorphic markers in the <Emphasis Type="Italic">CDKAL1</Emphasis> gene and in the <Emphasis Type="Italic">HHEX/IDE</Emphasis> locus

The increase in diabetes was noted at the turn of the 21st century. Patients with type 2 diabetes (T2DM) make up the majority of patients. Diabetes is a multifactorial disease. It arises from adverse effects of environmental factors on the body of genetically susceptible peoples. According to modern concepts, T2DM is a polygenic disease. Each of the involved genes contributes to the risk of developing of this disease. In our study, the association between polymorphic genetic markers rs7756992, rs9465871, rs7754840, and rs10946398 in the CDKAL1 gene and rs1111875 in the HHEX/IDE locus and T2DM in the Russian population were studied. Four hundred forty patients with type 2 diabetes and 264 healthy individuals without any signs of the disease were examined. The comparative analysis of distribution of genotypes and allele frequencies points to an association between polymorphic genetic markers rs7756992, rs9465871, and rs10946398 in the CDKAL1 gene and this disease. For the other polymorphic genetic markers (rs7754840 in the CDKAL1 gene and rs1111875 in the HHEX/IDE locus), no statistically significant associations are found. On the basis of these data, we can conclude that the CDKAL1 gene is associated with development of T2DM. For the HHEX/IDE locus, such an association is absent.     

Genetic structure of the populations of <Emphasis Type="Italic">Dactylorhiza ochroleuca</Emphasis> and <Emphasis Type="Italic">D. incarnata</Emphasis> (Orchidaceae) in the area of their joint growth in Russia and Belarus

We carried out an allozyme analysis to investigate polymorphism and genetic structure of the populations of D. incarnata and D. ochroleuca in regions of their joint growth in Russia and Belarus. We found that D. ochroleuca individuals in the populations of the Urals and Siberia, which are distant fragments from the main range of the species, do not differ significantly from individuals within the main part of the area (Belarus) on the basis of the allelic composition of eight gene loci. We revealed that D. ochroleuca and D. incarnata are differentiated by different alleles of the GDH locus. Thus, we established a genetic marker suitable to distinguish these closely related taxa. In addition to the GDH locus, D. ochroleuca and D. incarnata in the places of their joint growth, differ in the allelic structure of the PGI and NADHD loci. D. incarnata from the Urals and Siberia were polymorphic for both loci, and individuals from Belarus were polymorphic for one locus (PGI). In contrast, all D. ochroleuca individuals growing in sympatric populations with polymorphic D. incarnata were homozygous for the same alleles. Thus, comparison of the genetic structure of D. ochroleuca and D. incarnata points to the existence of a genetic isolation and a functioning isolation mechanism even under conditions of their joint growth. We found that the GDH locus in D. incarnata is polymorphic only in populations which grow together with D. ochroleuca, with exception a few examples. Thus, we conclude that variability of the GDH locus in D. incarnata is associated with hybridization with D. ochroleuca.     

Variation in particular biochemical indicators,cytokine and adipokine profiles of the blood,and the structural and functional parameters of the liver in patients with nonalcoholic fatty liver disease and different genotypes by the polymorphic locus A313G of the <Emphasis Type="Italic">GSTP1</Emphasis> gene

Variation in particular biochemical indicators, cytokine and adipokine profile parameters of the blood, and the structural and functional parameters of the liver have been studied in patients with nonalcoholic fatty liver disease (NAFLD) and different genotypes by the polymorphic locus A313G of GSTP gene (rs 1695). It has been established that the G allele of the GSTP gene (A313G) is significantly more frequently met in NAFLD patients than in healthy individuals. Higher activity of alanine aminotransferase and higher level of leptin, as well as lower adiponectin blood content, were recorded in the carriers of the G allele of the GSTP gene (A313G) as compared to patients with the given gene AA genotype. Higher interleukin-10 blood content was also observed in homozygous G allele carriers of NAFLD patients compared with the patients with the AA and AG genotypes. The patients with the G allele of the GSTP1 gene had a larger right lobe of liver than homozygous carriers of the given gene A allele.     

Multilocus analysis of the association of polymorphic variants of inflammation genes with ischemic stroke in Russians

Carriage frequencies of alleles and genotypes of polymorphic loci of inflammation genes (49A>G CTLA4, 41G>A and 87C>T PDE4D, ?590C>T IL4, ?308A>G TNF, 252G>A LTA, 874A>T IFNG, ?509С>Т, 869T>C and 915G>C TGFB1) were determined in a sample of 200 patients diagnosed with ischemic stroke and in the control group similar in gender and age (146 individuals), all ethnic Russians. The positive association of the allele PDE4D*87C (р = 0.028) and genotype TGFB1*?509Т/Т (р = 0.02) carriage with ischemic stroke was shown. The association of the disease with the carriage of the allele PDE4D*41А (р = 0.009) in individuals under the age of 60 and with carriage of the allele IFNG*874Т (р = 0.02) in individuals older than 60 was observed among the subgroups of patients stratified by age when they suffered the stroke compared to a control group of the same age. In subgroups stratified by gender, carriage of the genotype TGFB1*915G/G (р = 0.0015) was identified as a risk factor in male patients, while no significant differences between female patients and healthy women were observed. Multilocus analysis was undertaken to search for the association of several combinations of studied gene variants with ischemic stroke. The polymorphic locus–174G>C of the IL6 gene, for which an association with the disease was previously demonstrated, was also included in this analysis. The disease-predisposing biallelic combinations include the IL6*?174G, PDE4D*87C, TGFB1*?509Т and TGFB1*915G alleles. In the subgroups stratified by gender, the allelic combinations mainly include the similar risk alleles as in the total group, while between the subgroups stratified by age (patients who suffered the first stroke at the age of 18 and no older than 60 years and older than 60 years), greater differences were observed. However, a new risk allele, LTA*252G, was identified in combination with PDE4D*41А in women. These findings demonstrate the important role of inflammation in ischemic stroke. The identified single and combined markers may be used further to determine an individual risk for ischemic stroke.     

Dependence of endurance performance on <Emphasis Type="Italic">ACE</Emphasis> gene polymorphism in athletes

A group of elite 400-m distance runners carrying different alleles of the polymorphic angiotensinconverting enzyme (ACE) gene participated in an experiment that included aerobic exercise accompanied by measurement of the heart rate (HR) before, during, and after the exercise. Upon determination of the genotype for the ACE gene, the athletes were divided into three subgroups, carrying the II, ID, and DD alleles of the ACE gene. All athletes performed the same exercise: 25 min of running at an HR of 165–170 beats/min. The runners with the II genotype ran a significantly (p < 0.01) longer distance than the runners with the ID and DD genotypes. After the exercise, the HR recovery was the fastest in the runners with the II genotype.     

Association of immune system gene polymorphisms with quantitative traits pathogenetically important for chronic virus hepatitis

The IL4 C(?590)T, IL4RA Ile50Val, and TNF G(?308)A polymorphisms were tested for association with quantitative traits important for chronic virus hepatitis, including the levels of IL4, IL10, IL12, TNF-α, fibronectin, collagenase, the proteinase inhibitor, macroglobulin, and free and protein-bound (PBO) oxyproline. Allele A of the TNF G(?308)A polymorphism was associated with a lower TNF-α production by mononuclear cells, a higher production of IL4 and IL12, and a lower PBO level. The genotype CT of the IL4 C(?590)T polymorphism was associated with a high PBO level.     

Nucleotide sequences of the microsatellite locus <Emphasis Type="Italic">Du215 (arm)</Emphasis> allelic variants in the parthenospecies <Emphasis Type="Italic">Darevskia armeniaca</Emphasis> (Lacertidae)

Using monolocus PCR analysis with the pairs of primers designed for the Du215 locus of Darevskia unisexualis, allelic polymorphism at the orthologous locus in the populations of the related parthenospecies D. armeniaca was investigated. It was demonstrated that Du215 (arm) locus was polymorphic and in the populations of parthenospecies D. armeniaca (n = 127) represented by at least three allelic variants, differing from each other by the size and composition of microsatellite cluster, and by single nucleotide substitutions in flanking DNA. Unlike the Du215 locus, Du215 (arm) was shown contain not only GATA, but also (GACA) repeats, which were absent in D. unisexualis. Thus, in this study, the data on the molecular nature of allelic polymorphism at one of the microsatellite loci of the parthenospecies D. armeniaca were reported.     

Association of <Emphasis Type="Italic">FGFR2</Emphasis> (rs2981579) gene polymorphism with the risk of mesial occlusion

The molecular-genetic testing of the polymorphic rs2981579 (C>T) locus of the FGFR2 gene as the marker of increased predisposition to the development of mesial occlusion was carried out in 110 patients with mesial occlusion and 103 general-population control subjects from Ukraine. It was shown that polymorphism rs2981579 in gene FGFR2 is associated with mesial occlusion (OR = 1.67, 95% CI = 1.14–2.45, p = 0.009). Compared to CC carriers, TT+CT carriers had a 3.21-fold higher risk of mesial occlusion (95% CI = 1.57–6.57, p = 0.001). We found the protective effect of the homozygous allele C on mesial occlusion development (OR = 0.31, p = 0.001). This is the first published data on FGFR2 polymorphisms rs2981579 (C>T) in patients with mesial occlusion.     

Nucleotide polymorphisms of candidate genes of adaptive significance in the ural populations of <Emphasis Type="Italic">Larix sibirica</Emphasis> Ledeb.

The objectives of conservation and sustainable forest management require in depth study of genomes of woody plants and definition of their intraspecific genetic diversity. In recent years, an approach was developed based on the study of “candidate genes” that can potentially be involved in the formation of adaptive traits. In this study, we investigated nucleotide polymorphism of several adaptive candidate genes in the populations of Siberian larch (Larix sibirica Ledeb.) in the Urals. Representatives of this genus are among the most valuable and widely distributed forest tree species in Russia. From ten selected gene loci in the genome of L. sibirica, we isolated and investigated three loci, one of which (ABA-WDS) was sequenced in L. sibirica for the first time. The total length of the analyzed sequence in each individual amounted to 2865 bp. The length of locus alignment was from 360 bp to 1395 bp. In total, we identified 200 polymorphic positions. The most conservative is locus 4CL1-363, and the most polymorphic is locus sSPcDFD040B03103-274. The studied populations of L. sibirica are characterized by a high level of nucleotide polymorphism in comparison with other species and genuses (Picea, Pinus, Pseudotsuga, Abies) conifers plants (Hd = 0.896; π = 0.007; θ_W = 0.015). The most selectively neutral polymorphism (D _T =–0.997) was attributed to locus 4CL1-363, and polymorphism with high probability of adaptability (D _T =–1.807) was determined for the ABA-WDS locus. We identified 54 SNP markers, only five of which were nonsynonymous (9.26%) replacements. The average frequency of SNPs in the three studied loci of L. sibirica was one SNP in 53 bp. We detected unique SNP markers for eight populations, which could potentially be used to identify populations. Populations that are characterized by the highest number of unique SNP markers can be recommended for selection in order to preserve the gene pool of the species.     

Association of <Emphasis Type="Italic">NAT2</Emphasis> polymorphisms with susceptibility to psoriasis in the Moscow population

N-acetyltransferase 2 (NAT2) is a key enzyme of biotransformation phase II that metabolizes genotoxic compounds such as carcinogens and mutagens in different types of cells. A decreased NAT2 activity may correlate with sensitivity to harmful environmental factors, thus increasing susceptibility to different multifactorial diseases, including dermatologic conditions like psoriasis. A biochip developed in our lab to detect 17 NAT2 SNPs was tested on 279 clinical DNA samples from 180 patients with psoriasis and 99 healthy individuals, all residents of Moscow. Six polymorphisms that are most common in European populations (282C > T, 341T > C, 481C > T, 590G > A, 803A > G, and 857G > A) were detected. The NAT2 allele and genotype frequencies for individual SNPs did not differ between patients and healthy individuals. The frequency of the slow acetylation phenotype was increased in patients with type II psoriasis and in normosthenic patients as compared to controls (OR = 1.76, P = 0.177 and OR = 2.07, P = 0.050, respectively). Genotype 341C/C,481T/T,803G/G was significantly more frequent in patients who smoked at least one pack of cigarettes per day and in those who regularly consumed alcohol than in controls (OR = 7.42, P = 0.008 and OR = 106.11, P = 0.003, respectively). The frequency of genotype 341T/T, 481C/C, 590A/-, 803A/A was increased in patients with adverse reactions to medications (OR = 2.05, P = 0.099). Thus, our data suggest that some NAT2 genotypes in combination with certain lifestyles can be considered risk factors of psoriasis in the Moscow population.     

Genetic associations between ADHD and dopaminergic genes (<Emphasis Type="Italic">DAT1</Emphasis> and <Emphasis Type="Italic">DRD4</Emphasis>) VNTRs in Korean children

It is well known that dopaminergic genes affect the development of attention deficit hyperactivity disorder (ADHD) in various populations. Many studies have shown that variable number tandem repeats (VNTRs) located within the 3′-untranslated region of DAT1 and in exon 3 of DRD4 are associated with ADHD development; however, these results were inconsistent. Therefore, we investigated the genetic association between two VNTRs and ADHD in Korean children. We determined the VNTRs using PCR. We examined genotype and allele frequency differences between the experimental and control groups, along with the odds ratios, using Chi square and exact tests. We observed a significant association between the children with ADHD and the control group in the 10R/10R genotype of DAT1 VNTRs (p?=?0.025). In addition, the 11R allele of DAT1 VNTRs showed a higher frequency in the control group than in the ADHD group (p?=?0.023). Also, the short repeat (without 11R) and long repeat alleles (including 11R) were associated with ADHD (p?<?0.05). The analysis of DRD4 VNTRs revealed that the 2R allele is associated with ADHD (p?=?0.025). A significant result was also observed in long and short repeats (p?<?0.05). Additionally, ADHD subtypes showed that the DRD4 VNTRs are associated with combined and hyperactive-impulsive subtype groups (p?<?0.05). Therefore, our results suggest that DAT1 VNTRs and DRD4 VNTRs play a role in the genetic etiology of ADHD in Korean children.     

Genetic factors predisposing to a chronic course of virus hepatitis and liver fibrosis

The IL4 C(?590)T, IL4RA Ile50Val, and TNF G(?308)A polymorphisms were tested for association with the chronic development of virus hepatitis, the extent of which was inferred from the liver fibrosis stage. The frequency of allele A of the TNF G(?208)A polymorphism in patients with mild fibrosis was higher (24.5%) than in patients with moderate or severe fibrosis (13.4%) or cirrhosis (8.7%). The frequency of heterozygous genotype CT of the IL4 C(?590)T polymorphism significantly differed between cirrhosis (68.2%) and moderate or severe fibrosis (39.1%).     

Association between expression levels and growth trait-related SNPs located in promoters of the <Emphasis Type="Italic">MC4R</Emphasis> and <Emphasis Type="Italic">MSTN</Emphasis> genes in <Emphasis Type="Italic">Spinibarbus hollandi</Emphasis>

Melanocortin 4 receptor: (MC4R) and Myostatin (MSTN) are two important growth trait-related genes in animals. In this study, we showed that two SNPs, MC4R-719A>G and MSTN-519C>T, found in the promoters of the MC4R and MSTN genes, respectively, are both associated with growth traits in Spinibarbus hollandi. Furthermore, we observed that there were significant associations between the expression levels of the MC4R and MSTN genes and these two growth trait-related SNPs. The expression level of MC4R gene in brain was lower in GG genotype fish with extremely high growth performance than that in AA genotype fish with extremely low growth performance. Expression level of the MSTN gene in muscle was lower in TT genotype fish with extremely high growth performance than that in CC and CT genotype fish with lower growth performance. The results indicated that these SNPs located in the promoters of MC4R and MSTN are associated with growth-related traits through modification of gene expression levels. The MSTN and MC4R SNPs may have useful application in effective marker-assisted selection aimed to increase output in S. hollandi.