Significant Difference In Genotype Distribution Research Articles

Investigation on the association between IL-10 C819T gene polymorphisms and susceptibility to gastric cancer.

We conducted a case-control study to investigate the association between the interleukin-10 (IL-10) C819T polymorphism and susceptibility to gastric cancer in a Chinese population. A total of 157 patients with gastric cancer and 249 controls were consecutively enrolled from the Guizhou Provincial People's Hospital between October 2012 and February 2015. The polymerase chain reaction-restriction fragment length polymorphism technique was used to genotype for IL-10 C819T. As determined by χ2-test, there was a significant difference in genotype distributions of IL-10 C819T between gastric cancer patients and controls (χ2 = 7.09; P = 0.03). Based on unconditional logistic regression analysis, the TT genotype of IL-10 C819T was significantly associated with increased risk of gastric cancer when compared with that of the CC genotype [odds ratio (OR) = 2.24; 95% confidence interval (CI) = 1.17-4.26; P = 0.008]. In a dominant model, we found that the CT + TT genotype of IL-10 C819T was associated with susceptibility to gastric cancer compared to that of the CC genotype (OR = 1.63; 95%CI = 1.02-2.64). In a recessive model, the TT genotype of IL-10 C819T was correlated with a higher risk of gastric cancer when compared with that of the CC + CT genotype (OR = 1.75; 95%CI = 1.01-3.02). In conclusion, our study suggests that the IL-10 C819T polymorphism is associated with an increased risk of gastric cancer in co-dominant, dominant, and recessive models.

Genetic Analysis of BDNF, GNB3, MTHFR, ACE and APOE Variants in Major and Recurrent Depressive Disorders in Russia.

This study was conducted to explore the possibility of association between the single-nucleotide polymorphisms rs6264 of BDNF, rs5443 of GNB3, and rs1801133 of MTHFR; the In/Del polymorphism of ACE; and the ε2 allele of APOE and major depressive disorder (MDD) and recurrent depressive disorder (RDD) in an East Slavic population. Generalized multifactor dimensionality reduction (GMDR) method was applied to detect gene-gene interactions. One hundred fifty patients with RDD (101 females and 49 males) and 208 patients with MDD (115 females and 93 males) were included in the study. The comparison group consisted of 200 unrelated individuals. There was no significant difference in genotype distributions or allele frequencies between the controls and any of the diagnostic groups. Nevertheless, the frequency of the G allele of rs1801133 of MTHFR was higher in the RDD group and the frequency of the C allele of rs6264 of BDNF was higher in the MDD group. The difference between the controls and specific disease groups almost reached statistical significance (P = 0.08). A GMDR did not reveal optimal two- and three-dimensional models with significant prediction accuracies (P ˃ 0.05) for the MDD or RDD groups.

Correlation between PPARg2 gene Pro12Ala polymorphism and cerebral infarction in an Inner Mongolian Han Chinese population.

The variant of PPAR-g2 has been shown to promote the increase of carotid IMT in patients suffering from cerebral infarction and the Pro12Ala polymorphism in the peroxisome proliferator-activated receptorg2 (PPARg2) gene may be associated with cerebral infarction. However, due to the different genetic background, race, and regional variations of cerebral infarction patient, the results of investigations into this subject differ. The aim of this study was to investigate this polymorphism in relation to cerebral infarction among the Inner Mongolian Han Chinese population. A total of 574 Han Chinese individuals from Inner Mongolian were selected randomly, including 302 patients with cerebral infarction and 272 healthy controls. Polymerase chain reaction-restriction fragment length polymorphism was used to determine genotypes of the PPARg2 Pro12Ala variant and results were confirmed by direct sequencing. Genotype frequencies were found to be 90.7 and 91.9% for P/P, 8.6 and 7.7% for P/A, and 0.7 and 0.4 for A/A in the cerebral infarction and control groups, respectively. No statistically significant differences in genotype distribution were observed between the two groups (P > 0.05). Moreover, PPARg2 Pro12Ala genotype was not significantly associated with altered fasting blood glucose, blood pressure, or serum lipid profiles. After adjustment for gender, body mass index, and smoking habit, logistic regression was used to analyze the relationship between the Pro12Ala polymorphism and cerebral infarction (odds ratio = 0.888, 95% confidence interval = 0.106-7.460, P > 0.05), revealing that this variant was not the main pathogenic factor involved. Therefore, the Pro12Ala mutation of PPARg2 may not be associated with cerebral infarction in the Inner Mongolian Han Chinese population.

Association of four new candidate genetic variants with Parkinson's disease in a Han Chinese population.

Large-scale meta-analysis of genome-wide association data has identified six new risk loci (SIPA1L2, INPP5F, MIR4697, GCH1, VPS13C, and DDRGK1) for Parkinson's disease (PD). However, the characteristics of those loci in a Han Chinese population from mainland China are unknown. We examined genetic associations of VPS13C rs2414739, MIR4697 rs329648, GCH1 rs11158026, and SIPA1L2 rs10797576 with PD susceptibility in a Han Chinese population of 1028 sporadic PD patients and 1109 healthy controls. All subjects were genotyped for these loci using the Sequenom iPLEX Assay. We also conducted further stratified analysis according to age at onset and compared the clinical characteristics between minor allele carriers and non-carriers for each locus. However, we did not observe any significant difference in genotype distribution between PD patients and controls for the four loci, even after being stratified by age at onset. Besides, minor allele carriers cannot be distinguished from non-carriers based on their clinical features. Our findings first demonstrated that VPS13C rs2414739, MIR4697 rs329648, GCH1 rs11158026, and SIPA1L2 rs10797576 do not confer a significant risk for PD in Chinese population. Additional replication studies in other populations and functional studies are warranted to better validate the role of the four new loci in PD risk.

Relationship between glucokinase gene 6 tag single nucleotide polymorphism sites and type 2 diabetes mellitus

Objective To investigate the relationships between Glucokinase(GCK) gene 6 (tag single-nucleotide polymorphisms, tagSNPs)sites which named rs12702070, rs2971672, rs2268569, rs2268573, rs2300587 and rs1476891 polymorphisms and type 2 diabetes in Chinese Southern Han Population. Methods This study was designed as a case-control. 499 type 2 diabetes patients and 499 healthy controls were chosen. All subjects were from August 2013 to December 2014 in Zhongshan Affiliated Hospital of Sun Yat-sen University. 6 GCK tagSNPs sites were analyzed by improved multiple ligase detection reaction ( iMLDR), and genotype and allele frequency between T2D group and healthy controls could be determined by chi-square test, logistic regression analysis, and tagSNPs were further analyzed under three genetic modes(dominant, recessive and additive). What′s more, Haploview software was used to construct the haplotype of 6 GCK tagSNPs and the linkage disequilibrium(LD) and relationship between various GCK haplotype and T2D susceptibility could be analyzed. Results Genotype distribution of rs2268573, rs2300587, rs2268569 and rs1476891(χ2 were 3.361, 2.076, 0.582 and 0.918 respectively, all P>0.05) and allele frequency (χ2 were 0.222, 1.980, 0.590 and 0.851 respectively, all P>0.05) in T2D group were no significant differences with health controls. Significant differences in genotype distribution of rs2971672 and rs12702070 (χ2 were 6.896 and 7.990 respectively, all P 0.05), haplotype TA and CA reduce the individual risk of T2D with OR 0.81(95% CI: 0.66-1.00, P<0.05) and 0.78 (95% CI: 0.62-0.98, P<0.01)respectively. Conclusions The results indicated that GCK gene 2 tagSNPs sites included rs2971672 and rs12702070 imparts susceptibility to T2D in Han Chinese, but not rs2268573, rs2300587, rs2268569 and rs1476891.Haplotype TA and CA in rs2971672 and rs2300587 reduce the individual risk of T2D and four main haplotypes (TAG, TGG, TAT, CGG) in rs2268569, rs12702070 and rs1476891 have no relevance to T2D.(Chin J Lab Med, 2015, 38: 827-832) Key words: Diabetes mellitus, type 2; Glucokinase; Polymorphism, single nucleotide

Association between interleukin 8 −251 A/T and +781 C/T polymorphisms and osteosarcoma risk in Chinese population: a case–control study

Interleukin-8 (IL-8) is an angiogenic chemokine that plays a potent role in both development and progression of many human malignancies. However, there are no data about the role of IL-8 polymorphism in development of osteosarcoma. A hospital-based case-control study was conducted among 190 patients with osteosarcoma and 190 healthy controls to investigate the possible association between the IL-8 -251 A/T and +781 C/T polymorphisms, respectively, and the risk of osteosarcoma. Significant differences of genotype distribution were observed between osteosarcoma cases and controls at the IL-8 -251T/A genotypes. Compared with the IL-8 -251T/A homozygote TT, the heterozygous TA genotype was associated with significantly increased risk for osteosarcoma (odds ratio (OR) = 2.16, 95% confidence interval (CI) = (1.38-4.52), P = 0.021); the AA genotype was associated with increased risk for osteosarcoma (OR = 1.94, 95% CI = 1.31-3.83, P = 0.018). TA and AA combined variants were associated with increased risk for osteosarcoma compared with the TT genotype (OR = 1.72, 95% CI = 1.45-4.41, P = 0.023). Moreover, the genotype AA of IL-8 -251T/A carried a higher risk of osteosarcoma metastasis and later Enneking stages, compared with the TT genotype. However, the genotype and allele frequencies of IL-8 +781 C/T polymorphisms in osteosarcoma patients were not significantly different from controls. Our results showed that the IL-8 -251 A/T genotype was associated with increased risk for development and metastasis of osteosarcoma in Chinese Han population.

Association of -463G/A MPO gene polymorphism and risk of cervical intraepithelial neoplasia.

The MPO system plays an important role in the control of infections and the deletion of malignant cells. Nevertheless, alternations in the MPO system can lead to DNA damage and carcinogenesis. Polymorphisms in the MPO Gene have been associated with an increased expression of MPO and a higher risk for development of cancer. This study evaluates the association between -463G/A MPO gene polymorphism and the risk for CIN. The MPO gene polymorphism (-463G/A) was investigated in 616 women with cervical intraepithelial neoplasia and in 206 healthy women. Association between MPO gene polymorphism and risk of cervical intraepithelial neoplasia were analyzed by univariate and multivariable models. No significant difference in genotype distribution of the MPO gene polymorphism was observed in women with CIN and controls (p = 0.4; OR 1.2, 95 % CI 0.8-1.6). A subgroup analysis only including women with CIN did not show an association between -463G/A MPO gene polymorphism and risk for high-grade CIN (CIN 2/3) (p = 0.09; OR 1.5, 95 % CI 0.9-2.3). The investigated MPO gene polymorphism is not associated with risk for the development of cervical intraepithelial neoplasia.

Associations of Independent IL2RA Gene Variants with Intermediate Uveitis

PurposeThe genetic background for the concomitance of uveitis and other autoimmune diseases remains elusive. Here the role of two IL2RA gene variants (rs11594656 and rs12722495) was investigated in intermediate uveitis and HLAB27 acute anterior uveitis.Materials and MethodsOne hundred fifty-nine patients with HLAB27 acute anterior uveitis, 85 patients with intermediate uveitis, 138 HLAB27 negative controls and 100 HLAB27 positive controls were recruited for this case-control study. Main outcome measures were genotype distribution and allelic frequencies determined by polymerase chain reaction.ResultsThe frequencies of carriers of the minor allele at rs11594656 and rs12722495 were significantly different in patients with intermediate uveitis compared to HLAB27 positive and negative controls combined (p<0.05). For rs12722495 the minor G allele was protective (genotypic OR: 0.29 [0.12-0.69]), and for rs11594656 the minor A allele conferred risk (genotypic OR: 1.59 [1.09-2.32]). No significant differences in genotype distribution were found between patients with HLAB27 acute anterior uveitis and HLAB27 positive or negative control subjects.ConclusionsWe found rs11594656 and rs12722495 to be associated with intermediate uveitis but not with HLAB27 acute anterior uveitis. The genetic heterogeneity found at the IL2RA locus could help explain patterns of concomitance with other autoimmune diseases.

Single nucleotide polymorphisms of the EpCAM-coding gene TACSTD1 in patients with ovarian cancer and their potential translational aspects.

EpCAM is overexpressed in many neoplasms including ovarian cancer. We screened the EpCAM-coding gene TACSTD1 for single nucleotide polymorphisms (SNPs), which could alter ovarian cancer risk, impact upon disease progression, or alter binding of the therapeutic EpCAM-binding antibody, catumaxomab. DNA fragments of 10 healthy volunteers were analyzed to identify SNPs. Subsequently, DNA of ovarian cancer patients (n = 117) and age-matched healthy controls (n = 115) was genotyped by restriction fragment length polymorphism and pyrosequencing. TACSTD1 genotypes 4461T>C were cloned into a gene expression vector; Hek293 cells were subsequently used for stable transfection. FACS analysis of the transfected Hek293 cells was conducted with HO-3-the EpCAM binding site of catumaxomab-to determine antibody binding. One SNP was detected in exon 3 (4461T>C; rs1126497), resulting in an amino acid exchange at position 115 (Met115Thr). Another polymorphism was found in the 3'UTR (17225A>G; rs1421). Genotyping of patients and controls for these SNPs did not reveal significant differences in genotype distribution. Regarding 17225A>G, the homozygous AA-genotype was associated with diminished progression-free survival (PFS; p = 0.032). Overall survival, FIGO-stage, grading, and age did not differ significantly between genotypes. FACS analysis of transfected Hek293 cells overexpressing EpCAM 115Met/Thr showed binding of HO-3 to both proteins. The AA-genotype of 17225A>G seems to be associated with diminished PFS in ovarian cancer patients. The amino acid exchange resulting from 4461T>C does not appear to alter binding of HO-3, suggesting that treatment with catumaxomab can be offered to patients regardless of their TACSTD1-genotype.

Association between cannabinoid receptor type 2 Q63R variant and oligo/polyarticular juvenile idiopathic arthritis

Objectives: To investigate whether the functional variant Q63R of the cannabinoid 2 (CB2) receptor is associated with susceptibility to oligo/poly-articular juvenile idiopathic arthritis (JIA) and with its clinical features.Method: A total of 171 Italian children with oligoarticular/rheumatoid factor negative poly-articular JIA and 600 healthy controls were enrolled in the study and genotyped.Results: A significant difference in genotype distribution of the CB2 Q63R variant (CNR2 rs35761398) between oligo/poly-articular JIA patients and controls was found (p = 0.001). The R63 variant was associated with increased rates of relapse (p = 0.0001).Conclusions: This study indicates that the CB2 receptor contributes to susceptibility to oligo/polyarticular JIA and to the severity of its clinical course.

Lipoprotein lipase gene variants: Association with acute myocardial infarction and lipid profiles

BackgroundStudies showed that lipid metabolism disorders are significant risk factors for myocardial infarction and coronary artery disease (CAD). Therefore, genes involved in lipid and lipoprotein metabolism pathways such as lipoprotein lipase (LPL), are proper candidates for susceptibility to CAD. AimTo investigate the possible association between LPL gene variants (HindIII (rs320) and PvuII (rs285)), acute myocardial infarction (AMI) and serum lipid levels. Subjects and methodsThe study population consisted of 211 patients with a diagnosis of premature AMI, and 203 age-matched individuals with normal coronary angiograms as controls. Genotyping of HindIII and PvuII polymorphisms was done by the PCR-RFLP technique. ResultsAlthough the H+ and P+ alleles were more observed among the patients, there were no significant differences in genotype distributions and allele frequencies of HindIII and PvuII polymorphisms between patient and control subjects (P>0.05). Triglyceride levels were found to be significantly elevated in H+H+ and P+P+ genotypes compared to others (P<0.05). However, there was no association between HindIII and PvuII genotypes and HDL-C, LDL-C and cholesterol levels. ConclusionOur findings indicate that LPL-HindIII and PvuII polymorphisms are not associated with acute myocardial infarction but with triglyceride levels.

Single nucleotide polymorphisms of the inflamatory cytokine genes: interleukin-1B, tumor necrosis factors-A and tumor necrosis factor-B in adult patients with immune thrombocytopenia.

Immune thrombocytopenia (ITP) is an autoimmune disease characterized by thrombocytopenia due to platelet autoantibodies, causing an accelerated clearance of opsonized platelets by phagocytes. The etiology of ITP remains unclear, both genetic and environmental factors may have a role in the disease development. The aim of our study was to investigate a possible association of three single nucleotide polymorphisms (SNP) in the genes for interleukin beta (IL1B-511C/T), tumor necrosis factor beta (TNF+252G/A) and tumor necrosis factor alpha (TNFA-308G/A) with ITP. We have analyzed 125 adult patients with ITP and 120 healthy matched controls. Genotyping was performed by using PCR- RFLP methods. Our results demonstrated significantly different genotype distributions and allele frequencies for TNFB+252G/A in patients with ITP, p = 0.005 and p = 0.009 with Yates correction. We did not find any significant differences in the genotype distribution or allele frequencies for the other two genes. We have found significantly different genotype distribution and allele frequencies for TNFA-308G/A between patients with unresponsive and responsive ITP patients, p = 0.016 and p = 0.009. There were no significant differences in genotype distribution and allele frequencies for ILB-511C/T and TNFB+252G/A polymorphisms between those two groups of patients. We did not find any significant differences in genotype distribution and allele frequencies for all three polymorphisms between splenectomized and unsplenectomized ITP patients. The obtained data indicate that the A allele of TNFB+252G/A is more frequent in these patients than in the controls and that this polymorphism may play a significant role in disease susceptibility. The A allele of TNFA-308G/A was more frequent in patients with unresponsive ITP, indicating that this gene polymorphisms may contribute to therapy resistance.

The association of ApE1 -656T>G and 1349T>G polymorphisms and idiopathic male infertility risk.

In spite of variety studies in understanding of human reproductive and fertility, the underlying causes of male infertility remains undefined in about 50 % of cases. The polymorphism studies have a crucial role in diseases recognizing. Human apurinic/apyrimidinic endonuclease 1 (ApE1) is a multifunctional protein that has an important role in the base excision repair pathway. The present study was aimed to evaluate whether two polymorphisms -656T>G and 1349T>G ApE1 are related with the susceptibility to idiopathic male infertility. Samples were collected from 180 patients diagnosed with idiopathic male infertility and 120 control subjects and genotyped by tetra-primer amplification refractory mutation system PCR. We observed a significant difference in genotype distributions of -656T>G ApE1 polymorphism between infertile patients and controls (P = 0.0001). Our findings indicated individuals with the variant TG genotypes had a significant increased risk of idiopathic male infertility (OR 1.84, 95 % CI 1.09-3.11, P = 0.021), whereas the significant association between the 1349T>G polymorphism and idiopathic male infertility risk was not observed (P = 0.2). Our data suggest that the -656T>G ApE1 polymorphism may be associated with increased risk of idiopathic male infertility. Larger studies with more patients and controls are needed to confirm the results.

Variant TP53BP1 rs560191 G>C is associated with risk of gastric cardia adenocarcinoma in a Chinese Han population.

To investigate the association between gastric cardia adenocarcinoma (GCA) and ten functional single nucleotide polymorphisms (SNPs), including TP53BP1 rs560191 G>C, CASP8 rs1035142 G>T, CASP7 rs3127075 G>C, CASP7 rs7907519 C>A, and six C1orf10/CRNN variants. We performed a hospital-based case-control study to evaluate the genetic effects of these SNPs. Two hundred and forty-three GCA cases and 476 controls were enrolled in this study. A custom-by-design 48-Plex SNPscan(TM) Kit was used to determine their genotypes. When the TP53BP1 rs560191 GG homozygote genotype was used as the reference group, the GC genotype was associated with a significantly increased risk of GCA. The CC genotype was not associated with the risk of GCA compared with the GG genotype. None of the CASP8 rs1035142 G>T, CASP7 rs3127075 G>C, CASP7 rs7907519 C>A or the six C1orf10/CRNN polymorphisms showed a significant difference in genotype distributions between the cases and the controls. The results demonstrated that the functional polymorphism TP53BP1 rs560191 G>C might contribute to GCA susceptibility. However, the statistical power of our study was limited. Large, well-designed studies and further functional investigations are needed to confirm our findings.

Association of C5aR1genetic polymorphisms with coronary artery disease in a Han population in Xinjiang, China.

BackgroundComplement 5a receptor (C5aR) was demonstrated a receptor of complement 5a (C5a) which is involved in many inflammatory diseases. The functional responses attributed to C5a results from its interaction with its receptors C5aR, which stimulates food intake, plays a role in increasing the inflammatory response in adipose tissue as well as the cardiovascular and neural systems. However, There are unknown associations between the SNPs of C5aR1 gene and coronary artery disease (CAD).MethodsWe examined the role of the tagging single nucleotide polymorphisms (SNPs) of C5aR1 gene for CAD using a case–control design, and determined the prevalence of C5aR1 genotypes in 505 CAD patients and 469 age and sex-matched healthy control subjects of Han population.ResultsThe rs10853784 was found to be associated with CAD in dominant model (CC vs TT + CT, P = 0.004). The difference remained statistically significant after multivariate adjustment (OR = 1.430, 95% CI: 1.087 ~ 1.882, P = 0.011). There was no significant difference in genotype distributions of rs4577202 and rs7250152 between CAD patients and control subjects. The frequency of the haplotype (A-T-C) was significantly higher in the CAD patients than in the controls (P = 0.035), and the haplotype (A-C-T) was significantly lower in the CAD patients than in the control subjects in Chinese Han population (P = 0.002).ConclusionThe results of this study indicate that rs10853784 of C5aR1 gene are associated with CAD in Han population of China, and A-C-T haplotypes may be protective genetic marker and the A-T-C may be risk genetic marker for CAD in Chinese Han population.Virtual slidesThe virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/2054871241495194.

The intestinal fatty acid binding protein-2 Ala54Thr polymorphism is associated with diabetic retinopathy in Chinese population.

ObjectiveEndothelial dysfunction which is induced by serum saturated fatty acids increasing is one of pathogenesis of diabetic retinopathy (DR). The intestinal fatty acid binding protein-2 (FABP2) Ala54Thr polymorphism results in serum saturated fatty acids elevating. In the present study, we assessed the association of FABP2 gene polymorphism (Ala54Thr) with DR in Chinese population.Materials/MethodsIn this case–control association study, 810 T2DM patients were recruited. 420 patients with retinal neovascularization, microneurysms and hemorrhages were considered as cases (DR) and 390 patients with T2DM and no clinical signs of retinopathy (DNR), were recruited as controls. Genotypes for FABP2(Ala54Thr) polymorphisms were assessed with the PCR-RFLP method.ResultsA significant difference in genotype distribution and allele frequency was observed between cases and controls. Patients with DR had significantly higher frequency of the Ala/Thr + Thr/Thr genotypes compared to DNR group [62.6% vs. 46.2%; OR (95% CI), 1.95 (1.48-2.59); p < 0.001]. The DR group showed a significantly higher frequency of the the Thr allele compared to the DNR group [39.5% vs. 29.4%; OR (95% CI), 1.56 (1.16-2.09); p = 0.003]. Binary logistic analyses showed FFA levels (p = 0.014) and Ala54Thr (p = 0.011) were independent correlates of the presence of DR.ConclusionsWe examined that FABP2 polymophism on the Ala54Thr is significant and independent associated with DR.

The Variants Within the COL5A1 Gene are Associated with Reduced Risk of Anterior Cruciate Ligament Injury in Skiers.

The purpose of this study was to examine the association of the BstUI RFLP C/T (rs 12722) and DpnII RFLP C/T (rs 13946) COL5A1 polymorphisms, individually and as haplotypes, with anterior cruciate ligament ruptures in recreational skiers. Subjects were 138 male recreational skiers with surgically diagnosed primary anterior cruciate ligament ruptures. The control group consisted of 183 apparently healthy male recreational skiers, who were without any self-reported history of ligament or tendon injury. DNA was extracted from buccal cells donated by the subjects and genotyping was carried out using real-time PCR. The genotype distributions for both polymorphisms met Hardy-Weinberg expectations in both groups. There were no significant differences in genotype distribution of allele frequencies of COL5A1 BstUI RFLP C/T and COL5A1 DpnII RFLP C/T polymorphisms between the ACL rupture and control groups. The T-T (BstUI RFLP T, DpnII RFLP T) haplotype was the most common (55.6%). The haplotype T-C was not present in any of the subjects. There was an underrepresentation tendency of the C-T haplotype in the study group compared to controls under recessive mode of inheritance. Higher frequency of the COL5A1 BstUI RFLP C/T and COL5A1DpnII RFLP C/T polymorphisms haplotype is associated with reduced risk of anterior cruciate ligament injury in a group of apparently healthy male recreational skiers.

Human leukocyte antigen-G polymorphisms influence the clinical outcome in diffuse large B-cell lymphoma.

The role of HLA-G is extensively studied in cancer due to its inhibition of the immune response. Several polymorphisms in the HLA-G gene have been reported to significantly affect its expression. We, therefore, investigated whether functionally relevant HLA-G polymorphisms, HLA-G-725C/G/T, and HLA-G 14-base pair, have any influence on the susceptibility to diffuse large B-cell lymphoma (DLBCL) and its clinical course. The polymorphisms were genotyped in 207 previously untreated patients with DLBCL and 150 unrelated controls. A significant difference in genotype distribution of HLA-G polymorphic genotypes between the patients and controls was found. The frequencies of the HLA-G-725GG or the HLA-G-725GC genotype were lower, and those of the HLA-G ins/ins genotype were higher in the patients compared with the controls. Patients carrying the HLA-G-725CC genotype presented a higher probability of overall survival (OS) than subjects with other genotype combinations of HLA-G-725C/G/T (P = 0.003). The homozygous HLA-G del/del had a lower probability of OS than subjects carrying the HLA-G deletion/insertion (del/ins) or the HLA-G ins/ins genotype (P = 0.009). Two HLA-G genotype-based risk groups were defined according to the genotype distribution. The high-risk (HR) group presented a shorter OS than low-risk (LR) patients (P = 0.001). In a multivariate analysis adjusted for International Prognostic Index (IPI) factors, both the intermediate high/high IPI-risk group (P < 0.0001) and the HR genotype group (P = 0.004) independently increased the risk of death. This is the first study indicating an important role of HLA-G polymorphisms for the clinical course of DLBCL. The potential influence of HLA-G polymorphisms on the susceptibility to DLBCL thus deserves further study.

0501: Association of Cys311Ser polymorphism of paraoxonase-2 gene with myocardial infarction in the Tunisian male population

Paraoxonase 2 (PON2) has antioxidant properties similar to paraoxonase-1 and paraoxonase-3. However, in contrast to paraoxonase-1 and paraoxonase-3, paraoxonase-2 is not associated with high-density lipoproteins and may only exert its antioxidant function at the cellular level. PON2 may also play a role in the pathogenesis of arterial thrombosis and atherosclerosis. The purpose of the present study was to investigate the possible association between the Cys311Ser polymorphism of PON2 gene and myocardial infarction (MI) in the Tunisian male population A total of 700 unrelated Tunisian subjects including 321 patients with MI and 379 healthy controls were included in this study. Genomic DNA was extracted from peripheral blood leukocytes according to standard methods. PON2 genotypes were determined by PCRRFLP method. A significant difference in genotype distribution and allele frequencies was observed between MI patients and controls. Patients with MI had a frequency of 17.1% for CC genotype, 45.8% for the CS genotype and 37.1% for the SS genotype. The controls had a frequency of 26.1% for the CC genotype, 45.6% for the CS genotype and 28.2% for the SS genotype (χ 2 =10.58; p=0.005). The MI patient group showed a significantly higher frequency of the S allele compared to the controls (0.60 vs 0.51; χ 2 =11.16; p<0.001). In multivariate analysis, C311S polymorphism was independently associated with MI (p<0.001). Our results showed a significant and independent association between the PON2 C311S polymorphism (presence of S allele) and MI in the Tunisian male population.

Correlating interleukin-10 promoter gene polymorphisms with human cerebral infarction onset.

Evidence suggests that interleukin-10 (IL-10) deficiency exacerbates inflammation and worsens the outcome of brain ischemia. In view of the critical role of the single nucleotide polymorphic sites -1082 (A/G) and -819 (C/T) in the promoter region of the IL-10 gene, we hypothesized that they are associated with cerebral infarction morbidity in the Chinese Han population. We genotyped these allelic gene polymorphisms by amplification refractory mutation system-polymerase chain reaction methods in 181 patients with cerebral infarction (cerebral infarction group) and 115 healthy subjects (control group). We identified significant differences in genotype distribution and allele frequency of the IL-10-1082 A/G allele between cerebral infarction and control groups (χ2 = 6.643, P = 0.010). The IL-10-1082 A allele frequency was significantly higher in the cerebral infarction group (92.3%) than in the control group (86.1%) (P = 0.015). Moreover, cerebral infarction risk of the AA genotype was 2-fold higher than with the AG genotype (OR = 2.031, 95%CI: 1.134–3.637). In addition, AA genotype together with hypertension was the independent risk factor of cerebral infarction (OR = 2.073, 95%CI: 1.278–3.364). No statistical difference in genotype distribution or allele frequency of IL-10-819 C/T was found between cerebral infarction and control groups (P > 0.05). These findings suggest that the IL-10-1082 A/G gene polymorphism is involved in cerebral infarction, and increased A allele frequency is closely associated with occurrence of cerebral infarction.