The T-786C,G894T,and intron 4 VNTR (4a/b) polymorphisms of the endothelial nitric oxide synthase gene in prostate cancer cases

In previously conducted some studies it has been revealed that nitric oxide (NO) and nitric oxide synthase (NOS) system play a significant role in carcinogenesis. Nitric oxide (NO) is regulated by endothelial nitric oxide synthase (eNOS) enzyme which is one of the isoenzymes of NO synthase (NOS). In this study we have tried to come to a conclusion about whether eNOS gene T-786C, G894T and intron 4 VNTR (4a/b) polymorphisms might be considered as a risk factor causing prostate cancer (PCa) or not. A total of 200 subjects were included in this research. 84 patients with PCa (mean age 70.0 ± 6.4) and 116 healthy controls (mean age 69.9 ± 7.5) were recruited in this case-control study. Genomic DNA was extracted using the QIAamp DNA Blood Mini Kit (QIAGEN GmbH, Maryland, USA), according to the manufacturer’s guidelines. The T-786C, G894T and intron 4 VNTR (4a/b) polymorphisms were amplified using polymerase chain reation (PCR), detected by restriction fragment length polymorphism (RFLP). For T-786C polymorphism CC genotype [odds ratio (OR): 0.34, 95% confidence interval (CI): 0.15–0.78, P = 0.009)] and allele frequency (OR: 0.631, CI: 0.421–0.946, P = 0.026) is significant for control. In patients with PCa eNOS G894T polymorphism, both GT (OR: 0.069, CI: 0.027–0.174; P = 0.0001) and TT (OR: 0.040, CI: 0.013–0.123; P = 0.0001) genotype distribution, and also T allele frequency (OR: 0.237, CI: 0.155–0.362, P = 0.0001) were considered significant statistically. While genotype distribution for the other polymorphism eNOS, intron 4 VNTR (4a/b), is insignificant statistically, “a” allele frequency was found out to be significant (OR: 2.223, CI: 1.311–3.769, P = 0.003). In this study we indicated that genotype and allele frequencies of eNOS T-786C and G894T polymorphisms are statistically significant in patients with PCa. eNOS T-786C and G894T polymorphisms may be associated with PCa susceptibility in the Turkish population. In contrast, intron 4 VNTR (4a/b) polymorphism may not be related to PCa susceptibility in these patients.     

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.     

Associations of Polymorphic DNA Markers and Their Combinations with Multiple Sclerosis

Multiple sclerosis (MS) is regarded as multifactorial, polygenic disease; its development is the result of autoimmune and neurodegenerative processes which lead to multifocal lesions of the central nervous system. The aim of the study was to analyze associations between MS and polymorphic markers rs3129934 (C6orf10), rs1109670 (DDEF2/MBOAT2 gene), rs9523762 (GPC5 gene), rs28362491 (NFKB1 gene), rs10974944 (JAK2 gene), and rs2304256 (TYK2 gene). The material for the study was DNA samples of unrelated MS patients (N = 224) aged 17 to 67 years and individuals of a control group (N = 312) aged 18 to 66 years. Both samples were formed from the ethnic group of Russians. The results of the investigation demonstrated that, for women, MS was associated with genotypes rs3129934*C/T (p = 0.001, OR = 2.23), rs3129934*T/T (p = 0.028, OR = 4.04), and rs2304256*C/C (p = 0.049, OR = 1.6); for men, with genotype rs1109670*C/A (p = 0.017, OR = 2.06). In addition, using the APSampler algorithm, we identified combinations of alleles associated with increased risk of MS separately for women and men, in which the most frequent alleles of polymorphic markers were rs3129934*T, rs1109670*C, rs10974944*G, and rs2304256*C.     

Associations of MMP-2 −1306 C/T and MMP-9 −1562 C/T polymorphisms with breast cancer risk among different populations: a meta-analysis

The meta-analysis aims to investigate association between two matrix metalloproteinases (MMPs) polymorphisms (MMP-2 ?1306 C/T and MMP-9 ?1562 C/T) and breast cancer risk. Eligible studies were retrieved from relevant databases, based on predefined criteria. Quality assessment was evaluated by Newcastle–Ottawa Scale. Odds ratio (OR) with its 95% confidence interval (CI) was selected as the effect size for the meta-analysis. As a result, 13 studies were included. MMP-2 ?1306 C/T polymorphism was not significantly associated with breast cancer risk under all genetic models (P > 0.05). However, subgroup analysis stratified by ethnicity showed a significant association between MMP-2 ?1306 C/T polymorphism and reduced breast cancer risk in Asian populations under allelic model (OR 0.60, 95% CI 0.39–0.90, P = 0.02) and dominant model (OR 0.55, 95% CI 0.34–0.89, P = 0.02). MMP-9 ?1562 C/T polymorphism was significantly related to increased breast cancer risk under allelic model (OR 1.50, 95% CI 1.06–2.12, P = 0.02), additive model (OR 1.45, 95% CI 1.02–2.05, P = 0.04) and recessive model (OR 1.54, 95% CI 1.13–2.12, OR 0.007). A significant association between MMP-9 ?1562 C/T polymorphism and increased breast cancer risk in Caucasian was detected under most of the genetic models (P < 0.05). MMP-2 ?1306 C/T polymorphism might be significantly associated with reduced breast cancer risk in Asian, while MMP-9 ?1562 C/T might be closely related to increased breast cancer risk, especially in Caucasian.     

Analysis of the association of allelic variants of apolypoprotein E and interleukin 1 beta genes with multiple sclerosis in ethnic Tatars

Multiple sclerosis (MS) is a multifactorial disease of the central nervous system. The apolipoprotein E (APOE) and interleukin 1 β (IL1B) genes are considered to be candidate genes of MS. The aim of the study was to examine the hypothesis of the importance of APOE and IL1B gene polymorphisms in MS development in ethnic Tatars. DNA samples isolated by phenol-chloroform extraction from peripheral blood of 383 ethnic Tatars (120 MS patients and 263 healthy donors) were studied. 112C/R and 158R/C APOE gene polymorphisms as well as ?511T/C IL1B gene polymorphism were analyzed by polymerase chain reaction (PCR) followed by PCR product digestion by endonuclease. Odds ratio (OR) values were used for evaluation of the relative risk of alleles and(or) genotype combinations. It has been shown that APOE*2/*3 genotype is associated with low risk of the disease development (OR = 0.20) in women. A combined effect of APOE and IL1B allelic variants has been discovered indicating the increased risk of the disease development in the carriers of APOE*4 and IL1B*T/*T alleles (OR = 4.76).     

Genetic polymorphisms of <Emphasis Type="Italic">T-1131C APOA5</Emphasis> and <Emphasis Type="Italic">ALOX5AP SG13S114</Emphasis> with the susceptibility of ischaemic stroke in Morocco

Ischaemic stroke is a multifactorial disease. Genetic polymorphisms involved in lipid, inflammatory and thrombotic metabolisms play an important role in the development of ischaemic stroke. The present study aimed to assess the relationship between T1131C APOA5 and SG13S114 ALOX5AP polymorphisms and the risk of ischemic stroke in 175 cases and 201 controls. Genotyping was performed by high resolution melting and polymerase chain reaction restriction fragment length polymorphism methods. In the case of T-1131C APOA5, a modest risk of ischaemic stroke was noticed with CC (OR: 2.86; 95% CI = 1.24–6.58; Pc = 0.039) and C allele (OR: 1.54; 95% CI = 1.01–2.33; Pc = 0.014). For SG13S114ALOX5AP, a significant association was observed among subjects with TT (OR: 2.57; 95% CI =1.49–4.83; Pc = 0.009) and T allele (OR: 1.59; 95% CI = 1.16–2.19; Pc = 0.008). According to the risk factors of ischaemic stroke, a positive correlation was observed only between SG13S114 variant of ALOX5AP gene and hypertension (Pc = 0.026). Despite lower sample size, T-1131C APOA5 and SG13S114 variants could be considered an independent genetic risk factor of ischaemic stroke in Moroccan population.     

Association of <Emphasis Type="BoldItalic">lactase</Emphasis> 13910 C/T polymorphism with bone mineral density and fracture risk: a meta-analysis

A number of studies have investigated the association of lactase (LCT, C/T-13910) gene polymorphism with bone mineral density (BMD) and fracture risk, but previous results were inconclusive. In this study, a meta-analysis was performed to quantify the association of LCT (C/T-13910) polymorphism with BMD and fracture risk. Eligible publications were searched in the PubMed, Web of Science, Embase databases, Google Scholar, Yahoo and Baidu. Pooled weighed mean difference (WMD) or odds ratio (OR) with their 95% confidence interval (CI) were calculated using a fixed-effects or random-effects model. A total of nine articles with 8871 subjects were investigated in the present meta-analysis. Overall, the TT/TC genotypes of LCT 13910 C/T polymorphism showed significantly higher BMD than those with the CC genotype at femur neck (FN) (\(\hbox {WMD} = 0.011\,\hbox {g/cm}^{2}\), 95% CI \(=\) 0.004–0.018, \(P = 0.003\)). Besides, LCT 13910 C/T polymorphism may decrease the risk of any site fractures (for TT versus TC \(+\) CC, OR \(=\) 0.813, 95% CI \(=\) 0.704–0.938, \(P = 0.005\); for T allele versus C allele, OR \(=\) 0.885, 95% CI \(=\) 0.792–0.989, \(P = 0.032\)). However, there was no significant association of LCT 13910 C/T polymorphism with BMD at lumbar spine and risk of vertebral fractures under all genetic contrast models (all P values were \({>}0.05\)). The meta-analysis suggests that there are significant effects of LCT 13910 C/T polymorphism on BMD and fracture risk. Large-scale studies with different ethnic populations will be needed to further investigate the possible race-specific effect of LCT 13910 C/T polymorphism on BMD and fracture risk.     

Association of T-786C polymorphism of endothelial nitric oxide synthase 3 gene with the functional state of the myocardium in patients with ischemic heart disease combined with type 2 diabetes mellitus

The association of polymorphism T-786C of the endothelial NO-synthase gene NOS3 with the functional state of the left ventricle (LV) was studied among residents of the West Siberian region with ischemic heart disease (IHD), including that combined with diabetes mellitus type 2 (DMT2). Carriers of genotype–786TT had the greatest ejection fraction of the left ventricle in the group of patients without DMT2 (p = 0.012). This dependence was not revealed in the group of patients with IHD combined with DMT2. In the group with genotype–786TC, the frequency of left ventricular hypertrophy was higher among patients with DMT2 than patients without it (p = 0.025). There was no association between NOS3T–786C polymorphism and the severity of functional class of heart failure in both the groups.     

Association of the <Emphasis Type="Italic">POLG1</Emphasis> T(−365)C, <Emphasis Type="Italic">ANT1</Emphasis> G(−25)A,and <Emphasis Type="Italic">PEO1</Emphasis> G(−605)T polymorphisms with diabetic polyneuropathy in patients with Type 1 diabetes mellitus

This study is dedicated to a search for the association of the polymorphic markers T(?365)C of the POLG1 gene G(?25)A of the ANT1 gene and G(?605)T of the PEO1 gene with diabetic polyneuropathy (DPN) in Type 1 diabetes mellitus (DM1) patients. All patients were ethnic Russian Moscow residents, with DM1 records of no more than 5 years and DPN or DM1 records of more than 10 years but without DPN. We found that the polymorphic marker T(?365)C of POLG1 was associated with DPN in Russian patients with DM1. The carriers of the C allele and the CC genotype had a higher risk of DPN development (OR = 1.62; CI = 1.11–2.38; and OR = 1.76; CI = 0.99–3.13; respectively). In contrast, the T allele carrier status and the TT genotype were associated with a lower DPN risk (OR = 0.62, CI = 0.42–0.90; and OR = 0.61; CI = 0.35–1.07; respectively). We found no association of the polymorphic markers G(?25)A of ANT1 or G(?605)T of PEO1 with DPN in Russian DM1 patients living in Moscow.     

The GG genotype of the <Emphasis Type="Italic">HSPA1B</Emphasis> gene is associated with increased risk of glaucoma in northern Iran

Glaucoma is a heterogeneous eye disease characterized by optic nerve atrophy and visual field defects. The disease damages the retinal ganglion cells (RGC) and their functional axons. Heat shock proteins 70 (HSP70) are molecular chaperons that could have a protective effect in the development of glaucoma. Polymorphisms of HSP70 may alter protein function or expression and are associated with the susceptibility to glaucoma. The purpose of this study was to investigate whether the HSPA1B 1267A/G (rs1061581) and HSPA1L 2437T/C (rs2227956) variants contribute to glaucoma susceptibility. Genomic DNA samples from 169 patients with glaucoma and 178 healthy controls were genotyped using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Here we show that the presence of HSPA1B 1267GG genotype significantly increases the risk of glaucoma (OR = 3.16, 95% CI = 1.45–6.89, p = 0.003). The prevalence of HSPA1L 2437T/C genotypes in patients and controls did not differ significantly (p = 0.31, χ² = 2.32). However, large population based studies are required for further evaluation and confirmation of our finding.     

Carriage of 2R allele at VNTR polymorphous site of <Emphasis Type="Italic">XRCC5</Emphasis> gene increases risk of multiple sclerosis in an Iranian population

The DNA damage has considerably raised in active MS lesions compared to normal brains, indicating the possible role of DNA repairing genes in MS. In the current study, we sought to highlight the association between genetic polymorphisms of XRCC5 and XRCC6 genes, involved in Double Strand Breaks (DSBs) repair, and MS susceptibility. A total of 235 Iranian individuals; including 113 MS patients and 122 healthy controls were participated in this study. They were genotyped for the XRCC5 VNTR polymorphism by polymerase chain reaction (PCR). The genotype analysis of the XRCC6–61C>G polymorphism was performed using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique. The genotypic frequency of 2R/2R in the XRCC5 VNTR polymorphism was significantly higher in MS patients than controls (p = 0.048). The frequency of individuals with 2R allele was statistically significant in MS patients compared to controls (p = 0.041). Moreover, the frequency of 2R allele of the XRCC5 VNTR polymorphism was found to be significantly difference between MS patients and healthy groups (p = 0.003). The present study suggests that the presence of 2R allele in XRCC5 VNTR gene polymorphism may be a genetic risk factor for MS susceptibility in Iranian population.     

Association of polymorphic markers of chemokine genes,their receptors,and <Emphasis Type="Italic">CD14</Emphasis> gene with coronary atherosclerosis

Atherosclerosis represents an inflammatory response to the disturbance of the endothelial layer in the arterial bloodstream. In the present study, an analysis of associations of polymorphic markers for the genes controlling synthesis of proteins involved in atherosclerosis pathogenesis in coronary atherosclerosis (CA) patients (217 subjects) and in a control group (250 subjects) was conducted. The following genes were examined: rs991804 (CCL2 gene), rs1126579 (CXCR2 gene), rs4074 (CXCL1 gene), rs4073 (CXCL8 gene), rs333 (CCR5 gene), rs2471859 (CXCR4 gene), rs1801157 (CXCL12 gene), and rs2569190 (CD14 gene). Using the Monte Carlo and Markov chain (APSampler) method, allele/genotype combinations associated with both low and high CA risk were revealed. The most important findings included the following: CXCR4*T/T + CCL2*C + CCR5*I/I (P_perm = 1 × 10^–6, OR = 0.44, 95% CI 0.3–0.63), CXCR2*C + CD14*C + CXCL12*G + CCL2*C + CCR5*D (P_perm = 4 × 10^–6, OR = 5.78, 95% CI 2.34–14.28), CD14*C + CCL2*C/C + CCR5*D (P_perm = 6.3 × 10^–6, OR = 5.81, 95% CI 2.17–15.56), CXCL8*A + CXCR2*C + CD14*T + CXCR4*C (P_perm = 0.01, OR = 3.21, 95% CI 1.63–6.31).     

Maternal <Emphasis Type="Italic">MTHFR</Emphasis> polymorphism (677 C–T) and risk of Down’s syndrome child: meta-analysis

Methylenetetrahydrofolate reductase (MTHFR) is the most important gene that participates in folate metabolism. Presence of valine instead of alanine at position 677 and elevated levels of homocystein causes DNA hypomethylation which in turn favours nondisjunction. In this study, we conducted a meta-analysis to establish link between maternal single-nucleotide polymorphism (SNP) and birth of Down’s syndrome (DS) child. A total of 37 case–control studies were selected for analysis including our own, in which we investigated 110 cases and 111 control mothers. Overall, the result of meta-analysis showed significant risk of DS affected by the presence of maternal SNP (MTHFR 677 C–T OR = 0.816, 95% CI = 0.741–0.900, P<0.0001). Heterogeneity of high magnitude was observed among the studies. The chi-square value suggested a highly significant association between homozygous mutant TT genotype and birth of DS child (χ²=23.63, P=0.000). Genetic models suggested that ‘T’ allele possesses high risk for DS whether present in dominant (OR = 1.23, 95% CI = 1.13–1.34); codominant (OR = 1.17, 95% CI = 1.10–1.25) or recessive (OR = 1.21, 95% CI = 1.05–1.38) form. The analysis from all 37 studies combined together suggested that MTHFR 677 C–T is a major risk factor for DS birth.     

Polymorphisms in <Emphasis Type="Italic">VEGF-A</Emphasis> are associated with COPD risk in the Chinese population from Hainan province

In this study, we examined and validated how common variants contribute to susceptibility to chronic obstructive pulmonary disease (COPD) in the Han Chinese population. Here, we genotyped 18 nucleotide polymorphisms and evaluated their association with COPD using chi-square test and genetic model analysis (246 COPD patients and 350 controls), and found three SNPs that might cause a predisposition to COPD. Both rs3025030 and rs3025033 are located on chromosome 6 in VEGF-A. We found one risk allele ‘C’ from rs3025030 and another ‘G’ from rs3025033 using the log-additive model (OR 1.40; 95% CI 1.05–5.96; P = 0.022), (OR 1.38; 95% CI 1.03–1.84; P = 0.03). We also found another risk allele ‘A’ of rs9296092 in gene region ZBTB9-BAK1 by the allele model (OR 2.63; 95% CI 1.27–5.45; P = 0.0078), (adjusted OR 3.53; 95% CI 1.12–11.11; P = 0.031). We found a risk haplotype ‘CG’ associated with the risk of COPD (OR 1.39; 95% CI 1.04–1.86; P=0.028). Our results when compared with previous studies showed significant association between VEGF-A polymorphism and COPD. We also identified rs9296092 as a risk factor for COPD.     

Associations between interleukin-10 polymorphisms and susceptibility to juvenile idiopathic arthritis: a systematic review and meta-analysis

Background

Cytokine genes, including interleukin-10 (IL-10), are known to play important roles in the pathogenesis of juvenile idiopathic arthritis (JIA). This study aims to determine whether the IL-10 polymorphisms confer susceptibility to JIA.

Methods

A meta-analysis was performed on the associations between the IL-10-1082 G/A, -592 C/A, and -819 C/T polymorphisms and JIA. A total number of 7 studies involving 1,785 patients and 6,142 controls were considered in the meta-analysis.

Results

Meta-analysis of the IL-10-592 C/A and -819 C/T polymorphisms showed no association with JIA in the study participants, or in Caucasian or Middle Eastern participants. Meta-analysis of the IL-10-1082 A allele in all study participants, Caucasian and Middle Eastern, showed significant associations with RA (overall ORs were 1.17, 1.15, and 1.41, respectively). Meta-analysis of the AA versus GG genotype of the IL-10-1082 G/A polymorphism revealed significant associations with JIA (OR = 3.66, 95% CI = 1.44-9.29, P = 0.006) in participants from Middle Eastern countries. Additionally, meta-analysis of the GG versus AA+GA genotypes of the IL-10 -1082 G/A polymorphism revealed the GG genotype as the protective factor against JIA in the Middle Eastern subgroup (OR = 0.44, 95% CI = 0.20-0.94, P = 0,04). Moreover, meta-analysis of the IL-10 -1082 A allele in 4 studies on Hardy-Weinberg equilibrium showed a significant association with JIA (OR = 1.17, 95% CI = 1.07-1.28, P = 0.0009). No association was found between the IL-10 (-1082, -819, -592) ACC, ATA, and GCC haplotypes and JIA.

Conclusions

These results suggest that the IL-10-1082 G/A polymorphism confers susceptibility to JIA.

     

Gene–environment interactions between <Emphasis Type="Italic">ERCC2</Emphasis>, <Emphasis Type="Italic">ERCC3</Emphasis>, <Emphasis Type="Italic">XRCC1</Emphasis> and cadmium exposure in nasal polyposis disease

Gene–environment interactions have long been known to play an important role in complex disease aetiology, such as nasal polyposis (NP). The present study supports the concept that DNA repair gene polymorphisms play critical roles in modifying individual susceptibility to environmental diseases. In fact, we investigated the role of polymorphisms in DNA repair genes and cadmium as risk factors for Tunisian patients with NP. To the best of our knowledge, this is the first report on the impact of combined effects of cadmium and ERCC3 7122 A>G (rs4150407), ERCC2 Lys751Gln (rs13181) and XRCC1 Arg399Gln (rs25487) genes in the susceptibility to NP disease. Significant associations between the risk of developing NP disease and ERCC2 [odds ratio (OR)?=?2.0, 95 % confidence interval (CI)?=?1.1–3.7, p?=?0.023] and ERCC3 (OR?=?2.2, 95 % CI?=?1.2–4.1, p?=?0.013) genotypes polymorphisms were observed. Blood concentrations of Cd in NP patients (2.2 μg/L) were significantly higher than those of controls (0.5 μg/L). A significant interaction between ERCC3 (7122 A>G) polymorphism and blood-Cd levels (for the median of blood-Cd levels: OR?=?3.8, 95 % CI?=?1.3–10.8, p?=?0.014 and for the 75th percentiles of blood-Cd levels: OR?=?2.7, 95 % CI?=?1.1–7.2, p?=?0.041) was found in association with the risk of NP disease. In addition, when we stratified ERCC2, ERCC3 and XRCC1 polymorphism genotypes by the median and 75th percentiles of blood-Cd levels, we found also significant interactions between ERCC2 (Lys751Gln) and ERCC3 (7122 A>G) genotypes polymorphism and this metal in association with NP disease. However, no interaction was found between XRCC1 (Arg399Gln) polymorphism genotypes and Cd in association with NP disease.     

GL261 glioma tumor cells respond to ATP with an intracellular calcium rise and glutamate release

Necrotizing enterocolitis (NEC) is one of the most severe and unpredictable complications of prematurity. There are two possible mechanisms involved in the pathogenesis of NEC: individual inflammatory response and impaired blood flow in mesenteric vessels with secondary ischemia of the intestine. The aim of this study was to evaluate the possible relationship between polymorphisms: Il-1β 3953C>T, Il-6 ?174G>C and ?596G>A, TNFα ?308G>A, and 86 bp variable number tandem repeat polymorphism of interleukin-1 receptor antagonist (Il-1RN VNTR 86 bp) and three polymorphisms that may participate in arteries tension regulation and in consequence in intestine blood flow impairment: eNOS (894G>T and ?786T>C) and END-1 (5665G>T) and NEC in 100 infants born from singleton pregnancy, before 32 + 0 weeks of gestation, exposed to antenatal steroids therapy, and without congenital abnormalities. In study population, 22 (22%) newborns developed NEC. Surgery-requiring NEC was present in 7 children. Statistical analysis showed 20-fold higher prevalence of NEC in infants with the genotype TT [OR 20 (3.71–208.7); p = 0.0004] of eNOS 894G>T gene polymorphism. There was a higher prevalence of allele C carriers of eNOS 786T>C in patients with surgery-requiring NEC [OR 4.881 (1.33–21.99); p = 0.013]. Our investigation did not confirm any significant prevalence for NEC development in another studied genotypes/alleles. This study confirms the significant role of polymorphisms that play role in intestine blood flow. Identifying gene variants that increase the risk for NEC development may be useful in screening infants with inherent vulnerability and creating strategies for individualized care.     

Associations of <Emphasis Type="Italic">CTLA4</Emphasis> +49 A/G Dimorphism and HLA-DRB1*/DQB1* Alleles With Type 1 Diabetes from South India

The aim of present study was to elucidate the association of CTLA4 +49 A/G and HLA-DRB1*/DQB1* gene polymorphism in south Indian T1DM patients. The patients and controls (n?=?196 each) were enrolled for CTLA4 and HLA-DRB1*/DQB1* genotyping by RFLP/PCR-SSP methods. The increased frequencies of CTLA4 ‘AG’ (OR?=?1.99; p?=?0.001), ‘GG’ (OR?=?3.94; p?=?0.001) genotypes, and ‘G’ allele (OR?=?2.42; p?=?9.26?×?10^?8) were observed in patients. Reduced frequencies of ‘AA’ (OR?=?0.35; p?=?7.19?×?10^?7) and ‘A’ (OR?=?0.41; p?=?9.26?×?10^?8) in patients revealed protective association. Among HLA-DRB1*/DQB1* alleles, DRB1*04 (OR?=?3.29; p?=?1.0?×?10^?5), DRB1*03 (OR?=?2.81; p?=?1.9?×?10^?6), DQB1*02:01 (OR?=?2.93; p?=?1.65?×?10^?5), DQB1*02:02 (OR?=?3.38; p?=?0.0003), and DQB1*03:02 (OR?=?7.72; p?=?0.0003) were in susceptible association. Decreased frequencies of alleles, DRB1*15 (OR?=?0.32; p?=?2.55?×?10^?7), DRB1*10 (OR?=?0.45; p?=?0.002), DQB1*06:01 (OR?=?0.43; p?=?0.0001), and DQB1*05:02 (OR?=?0.28; p?=?2.1?×?10^?4) in patients were suggested protective association. The combination of DRB1*03+AG (OR?=?5.21; p?=?1.4?×?10^?6), DRB1*04+AG (OR?=?2.14; p?=?0.053), DRB1*04+GG (OR?=?5.21; p?=?0.036), DQB1*02:01+AG (OR?=?4.44; p?=?3.6?×?10^?5), DQB1*02:02+AG (OR?=?20.9; p?=?9.5?×?10^?4), and DQB1*02:02+GG (OR?=?4.06; p?=?0.036) revealed susceptible association. However, the combination of DRB1*10+AA (OR?=?0.35; p?=?0.003), DRB1*15+AA (OR?=?0.22; p?=?5.3?×?10^?7), DQB1*05:01+AA (OR?=?0.45; p?=?0.007), DQB1*05:02+AA (OR?=?0.17; p?=?1.7?×?10^?4), DQB1*06:01+AA (OR?=?0.40; p?=?0.002), and DQB1*06:02+AG (OR?=?0.34; p?=?0.001) showed decreased frequency in patients, suggesting protective association. In conclusion, CTLA4/HLA-DR/DQ genotypic combinations revealed strong susceptible/protective association toward T1DM in south India. A female preponderance in disease associations was also documented.     

Association of genes of different functional classes with type 1 diabetes

The genetic structure of susceptibility to type 1 diabetes (T1D) in the population of Tomsk was studied. We had a group of T1D patients (N = 285) and a population sample (N = 300) and we studied 58 SNPs localized in the 47 genes which products are involved in various metabolic pathways and processes as fibrogenesis, endothelial dysfunction, and inflammation. Genotyping was performed by mass spectrometry using the Sequenom MassARRAY system (United States). We compared the group of T1D patients and the population sample and found an association with the predisposition to disease for seven markers: rs3765124 of the ADAMDEC1 gene, genotype AA (p = 0.004), allele A (p = 0.033); rs1007856 of the ITGB5 gene, genotype TT (p = 0.015), allele T (p = 0.036); rs20579 of the LIG1 gene, genotype CC (p = 0.004), allele C (p = 0.002); rs12980602 of the IFNL2 gene, allele C (p = 0.029); rs4986819 of the PARP4 gene, allele C (p = 0.044); rs1143674 of the ITGA4 gene genotype GG (p = 0.002); rs679620 of the MMP3 gene, genotype AA (p = 0.008). Thus, the products of genes associated with T1D belong to different molecular classes: metalloproteases (ADAMDEC1, MMP3), cytokines (IL28A), cell surface receptors (ITGA4), adhesion molecules (ITGB5), DNA ligases (LIG1), and ribosyltransferase enzymes (PARP4). The ADAMDEC1, ITGA4, and ITGB5 genes belong to two biological processes: cell communication and signal transduction. The LIG1 and PARP4 genes regulate the metabolism of nucleic acids, MMP3 is involved in the regulation of protein metabolism, and the IFNL2 is involved in the immune response.     

Influences of −482C&gt;T and 3238G&gt;C polymorphisms of the <Emphasis Type="Italic">Apolipoprotein C3</Emphasis> gene on prevalence of metabolic syndrome

Apolipoprotein C3 (ApoC3) plays a regulatory role in triglyceride (TG) metabolism. The higher level of TG can be a cause in pathogenesis of the vascular diseases or metabolic syndrome (MetS). In this study, we examined the associations of ApoC3 polymorphisms (?482C>T rs2854117 and 3238G>C rs5128) with Korean MetS patients. A total of 835 subjects were investigated, including 320 patients with MetS and 515 healthy subjects. The genotype analysis of the ApoC3 polymorphisms was performed by polymerase chain reaction-restriction fragment length polymorphism methods. Of the two polymorphisms studied, we observed a significant difference in the ?482C>T polymorphism between the MetS and control groups. The TT genotype of the ?482C>T polymorphism was associated with increased risk for MetS, compared with the controls (OR 1.627, 95 % CI 1.075–2.463, P = 0.021). The association was female-specific. No associations were found for the risk of MetS in the 3238G>C polymorphism. Haplotypes composed of two polymorphisms, however, were associated with MetS susceptibility in only male group. The 3238G>C polymorphism was significantly associated with TG levels (P = 0.013). Our data suggest that the ApoC3 ?482C>T polymorphism is associated with increased MetS susceptibility in the Korean population.