Chronic obstructive pulmonary disease (COPD) is a complex lung disease characterized by progressive airflow limitation and abnormal inflammatory response of the lungs to inhaled noxious particles or ...gases. COPD pathogenesis has been linked to oxidative stress and systemic inflammation. We aimed to assess the association of cytokines and inflammatory genes polymorphisms and their combinations with COPD. SNPs of the inflammatory genes
FASLG
(rs763110),
IL19
(rs2243193),
IL20
(rs2981573),
IL24
(rs291107),
PPBP
(rs352010),
IL4
(rs2243250),
IL4
(rs2070874),
С5
(rs17611),
FAS
(rs1800682),
IL4RA
(rs1805010), and
TGFb1
(rs1800469) were genotyped by the real-time polymerase chain reaction (PCR) among 601 COPD patients and 617 controls. Significant associations with COPD in the study group under an additive genetic model were identified for
IL19
(rs2243193) (
P
= 0.00001, OR = 0.73),
IL4
(rs2243250) (
P
= 0.024, OR = 1.27),
IL4
(rs2070874) (
P
= 0.00001, OR = 0.62), and for
PPBP
(rs352010) under the recessive model (
P
= 0.00001, OR = 2.34). Using the APSampler algorithm, we obtained gene–gene combinations that remained significantly associated with COPD; the
A
allele of
IL19
(rs2243193) and
C
allele of
PPBP
(rs352010) were the core elements of the majority of protective patterns associated with COPD. The highest risk of COPD was conferred by combination of alleles:
G
of
IL12A
(rs2243115) with
A
of
IL13
(rs20541) and
C
of
IL4
(rs2070874) (OR = 2.72). The receiver operating characteristic (ROC) analysis resulted in an area under the curve (AUC) of 0.895 (95%CI 0.874–0.916) for model including SNPs: the
A
allele of
IL19
(rs2243193) and
AA
genotype of
IL20
(rs2981573) combination,
IL19
(rs2243193),
IL12A
(rs2243115),
PPBP
(rs352010), and
IL4
(rs2070874) together with age and smoking pack/years, indicating a high ability of the model to correctly classify individuals with and without COPD.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
The distribution of allele and genotype frequencies of Alu(I/D) polymorphic sites in the
COL13A1
and
LAMA2
genes coding extracellular matrix protein subunits was characterized in an ethnically ...homogeneous group (Tatars from the Republic of Bashkortostan, Russia). It was established that the frequency of individuals with the
COL13A1
*
D
/*
D
genotype was higher in the senile age period. The
LAMA2
*
I
/*
D
genotype was predisposing to longevity among women. According to the observed results, the frequency of the
LAMA2
*
I
/*
D
genotype was increased in senile individuals older than 90 years. The observed associations can be explained on the basis of the contemporary view by the importance of Alu elements in gene expression regulation at transcriptional and post-transcriptional levels, the involvement of collagen and laminin in maintaining the structure and function of the extracellular matrix, and the relationship between the extracellular matrix state, pathological changes and aging.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
The objective of the study:
to evaluate the efficacy of treatment of extensive drug resistant tuberculosis (XDR-TB) in patients with different genotypes in the biotransformation system
NAT2 ...(rs1041983,
rs1799930, rs1799931, rs1801280)
and
CYP2B6
genes
(rs3745274).
Subjects and methods.
The study involved patients undergoing in-patient treatment at Republican Clinical TB Dispensary in Ufa from 2016 to 2018. XDR TB group included 210 people; the control group included 343 healthy donors. Molecular genetic analysis was performed on DNA samples isolated from peripheral blood leukocytes. Genotyping of polymorphic loci was carried out by kompetitive allele specific PCR (KASP).
Results.
It was revealed that polymorphic loci
rs1799931
of
NAT2
gene and
rs3745274
of
CYP2B6
gene were associated with the risk of developing XDR TB. Regression analysis detected combinations of the predictor genotypes of
rs1799931*G/A
×
rs3745274*G/T
and
rs1799931*G/G
×
rs37455274*(G/G
+
T/T)
, that significantly reduce efficacy of XDR TB treatment.
Essential hypertension is a common disease with fatal clinical complications. Epidemiological and family studies have confirmed the role of genetic predisposition in its development. Hypertensive ...patients have been shown to have an altered profile of pro- and anti-inflammatory cytokines. The aim of our investigation was to reveal the association of interleukin-6, interleukin-12, and interleukin-10 gene polymorphisms with essential hypertension and its clinical complications in a Tatar ethnic group from Bashkortostan, Russia. The study involved 362 hypertensive patients and 244 healthy subjects from this Tatar ethnic group (Bashkortostan, Russia). DNA was isolated from whole venous blood using phenol-chloroform extraction by the standard method. IL6 -572 G/C, IL12B 1159 C/A, and IL10 -627 C/A genotypes were typed using polymerase chain reaction followed by restriction enzyme digestion. We found that the IL10 -627 *C/*C genotype was associated with decreased risk of hypertension (OR = 0.64, P = 0.035). IL6 genotypes and allele distribution did not differ significantly between subjects with and without hypertension, but the IL6 -572 *G/*G genotype frequency was found to be significantly higher among those patients who had stroke, compared with normotensive control subjects (P = 0.036). Carriers of the IL12B 1159 *A/*A genotype had a lower risk of stroke (OR = 0.38, P = 0.028). Our study has shown the association between IL10 -627 C/A polymorphism and essential hypertension in the Tatar ethnic group from Bashkortostan, Russia. The IL10 -627*C/*C genotype was found to be protective against hypertension. We also demonstrated that hypertensive patients with the IL12B *A/*A and IL6 *G/*G genotypes had increased risk of stroke. Our results suggest a role for cytokines in cardiovascular disease development in the Tatar ethnic group, but further investigation is needed.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
With the intent to identify informative predictors of myocardial infarction (MI) development in an ethnically homogenous group of Russian men after MI (255 subjects) and in a corresponding control ...group (257 subjects), an analysis of genotype frequency distribution for polymorphic DNA markers (SNP) rs16944 (−511C>T, IL1B gene), rs1800796 (−572G>C, IL6 gene), rs1800872 (−592C>A, IL10 gene), rs3212227 (1159A>C, IL12B gene), rs1800629 (−308G>A, TNF), rs909253 (252A>G, LTA), rs767455 (36A>G, TNFRSF1A) was conducted. Using the Monte Carlo method and a Markov chain (APSampler), allele combinations associated both with decreased and increased MI risk were revealed. The most significant results were obtained for IL6*C/C (P = 3 × 10⁻⁴, OR = 6.3 CI 2.37–16.75), LTA*A + IL6*G/G (FDR = 2.3 × 10⁻⁴, OR = 0.25 CI 0.14–0.46), LTA*G/G + IL12B*A/A (FDR = 0.0053, OR = 4.92 CI 1.8–13.33), TNF*G + LTA*G/G + TNFRSF1A*A (FDR = 0.013, OR = 4.38, CI 1.6–12.01), TNFRSF1A*G + IL10*A/A + IL12B*C (FDR = 0.016, OR = 8.79, CI 2.17–35.63), TNF*G + LTA*G/G + IL10*C (FDR = 0.0105, OR = 3.54 CI 1.55–8.09).
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
For the first time, a study of genetic factors of longevity was conducted in the prevalent populations of 2511 residents of the Republic of Bashkortostan—Russians, Bashkirs, and Tatars. We ...investigated the polymorphic markers in the genes of the antioxidant defense enzymes—
SOD1
(rs2070424),
SOD2
(rs4880), and
SOD3
(rs1799895). We detected ethnicity-specific patterns of the distribution of genotype frequencies between Bashkir and Russian groups (rs2070424 of the
SOD1
gene,
P
= 0.003), as well as between Tatars and the groups of Russians and Bashkirs (rs4880 of the
SOD2
gene,
P
< 0.001 and 0.035, respectively). We found associations of the polymorphic markers in SOD family genes with age. Among Russians, the chances to attain longevity were higher in the
SOD1
*А/А genotype carriers (OR = 1.025,
P
= 0.001) and lower in those with the
SOD1
*А/G (OR = 0.975,
Р
= 0.001) and
SOD2
*А/А (OR = 0.985,
Р
= 0.002) genotypes. Among Tatars, we observed a decrease in the
SOD2
*A/A (OR = 0.989,
Р
= 0.029) and
SOD2
*V/V (OR = 0.985,
Р
< 0.001) genotype frequencies and an increase in the
SOD2
*A/V genotype frequency (OR = 1.023,
P
< 0.001). The analysis of genotype and/or allelic combinations of the studied polymorphic loci revealed 12 patterns associated with longevity among Tatars. The
SOD1
*А and
SOD3
*С alleles were present in most of the identified combinations. The
SOD2
rs4880 polymorphic marker was indicative of longevity: combinations including the
SOD2
*V/V genotype were associated with lower chances of achieving longevity (OR ≤ 0.45,
P
FDR
≤ 0.0003), and combinations including the
SOD2
*A/V genotype were associated with higher chances of achieving longevity (OR ≥ 2.92,
P
FDR
≤ 1.24 × 10
–6
).
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Chronic obstructive pulmonary disease (COPD) is a complex chronic inflammatory disease of the respiratory system. Smoking is a major risk factor of COPD. Neurotransmitter system genes were tested for ...association with COPD using DNA samples from COPD patients (
N
= 601) and healthy subjects (
N
= 617). SNPs of
GRIK3
(rs534131),
GRIN2B
(rs7301328 and rs1805476),
GRIA1
(rs2195450),
GRIN1
(rs6293),
GABBR2
(rs3750344),
BDNF
(rs6265 and rs11030107), and
ANKK1
(rs1800497) were genotyped by real-time polymerase chain reaction (PCR). Significant associations were detected for
GRIK3
(rs534131) (
P
= 0.009, OR = 1.42 in a dominant model),
GRIA1
(rs2195450) (
P
= 0.015, OR = 1.35 in a dominant model),
GRIN1
(rs6293) (
P
= 0.036, OR = 0.79 in a log-additive model), and
GRIN2B
(rs7301328) (
P
= 0.0009, OR = 0.54 in a recessive model).
GRIK3
(rs534131) (
P
= 0.0001, OR = 1.68 in a dominant model) and
GRIN2B
(rs7301328) (
P
= 0.001, OR = 0.52 in a recessive model) were significantly associated with COPD only in smokers. Associations of
GRIN1
(rs6293) (
P
= 0.0001, OR = 0.36 in a dominant model),
GRIA1
(rs2195450) (
P
= 0.0018, OR = 2.40 in a log-additive model), and
BDNF
(rs11030107) (
P =
0.005, OR = 2.86 for TT) with COPD were detected in nonsmokers. Lower smoking index were observed in carriers of the
GRIK3
(rs534131) genotype GG and
GRIA1
(rs2195450) genotype GG (
P
= 0.028 and 0.0001, respectively). The level of nicotine dependence was significantly higher in carriers of the rare allele A of
GRIK3
(rs534131A>G) and the genotype GC of
GRIN2B
(rs7301328C>G) (
P
= 0.011 and 0.023, respectively). Informative genotype and allele combinations significantly associated with COPD were identified using the APSampler algorithm and included
GRIN2B
rs2268132*
T
,
GRIN2B
rs7301328*
G
,
GRIN2B
rs1805476*
C
,
ANKK1
rs1800497*
G
,
GABBR2
rs3750344*
A
,
CHRNA5
rs16969968*
T
,
CHRNA3
rs1051730*
A
,
HTR2A
rs6313*
CC
, and
GRIA1
rs2195450*
G.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
New one-dimensional Hardy-type inequalities for a weight function of the form $x^\alpha(2-x)^\beta$ for positive and negative values
of the parameters $\alpha$ and $\beta$ are put forward.
In some ...cases, the constants in the resulting one-dimensional inequalities are sharp.
We use one-dimensional inequalities with additional terms to establish multivariate inequalities with weight functions depending
on the mean distance function or the distance function from the boundary of a domain. Spatial inequalities are proved in arbitrary domains,
in Davies-regular domains, in domains satisfying the cone condition, in $\lambda$-close to convex domains,
and in convex domains. The constant in the additional term in the spatial inequalities depends on the volume or
the diameter of the domain. As a consequence of these multivariate inequalities,
estimates for the first eigenvalue of the Laplacian under the Dirichlet boundary conditions in various classes of domains are established.
We also use one-dimensional inequalities to obtain new classes of meromorphic univalent functions in simply connected domains. Namely,
Nehari-Pokornii type sufficient conditions for univalence are obtained.
The main function of matrix metalloproteinases is the degradation of the extracellular matrix and participation in signal transduction. In addition, it is known that they are involved in all stages ...of the progression of the tumor process. The activity of metalloproteinases can be regulated by interactions with specific inhibitors of matrix metalloproteinases, so the latter are also able to participate in tumor growth. The genes of matrix metalloproteinases and their inhibitors, as well as many other genes, are characterized by polymorphism. We have analyzed the frequency distribution of the alleles and genotypes of the polymorphic loci rs1799750 and rs494379 of the
MMP1
gene, rs2285053 of the
MMP2
gene, rs3025058 of the
MMP3
gene, rs3918242 and rs17576 of the
MMP9
gene, rs2276109 of the
MMP12
gene, rs8179090 of the
TIMP2
gene, and rs9619311 of the
TIMP3
gene in 314 patients with gastric cancer, as well as in 339 unrelated healthy individuals from the Republic of Bashkortostan. It was shown that the markers of the increased risk of developing gastric cancer are the genotypes rs1799750*
1G
/
2G
of the
MMP1
gene and rs2276109*
A
/
A
of the
MMP12
gene for Tatars and the genotype rs9619311*
T
/
T
of the
TIMP3
gene for Russians. The association of the rs494379*
G
allele of the
MMP1
gene and increased risk of developing malignant tumors of the stomach were reported in men. Using the APSampler algorithm, we identified combinations of alleles/genotypes associated with an increased and a reduced risk of developing gastric oncopathologies. The data obtained confirm the influence of the studied polymorphic variants of the genes of matrix metalloproteinases and their tissue inhibitors on the risk of developing gastric cancer and are important for understanding the genetic structure of the studied pathology.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
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