IL-10 promoter single nucleotide polymorphisms are significantly associated with resistance to leprosy

The minor haplotype −3575A/-2849G/-2763C in IL-10 promoter has been defined as a marker of disease resistance to leprosy and its severity in Brazilian population. Our investigation of six single-nucleotide polymorphisms (SNPs) in IL-10 promoter in 282 Indian leprosy patients and 266 healthy controls by direct PCR sequencing, however, showed that the extended haplotype: −3575T/-2849G/-2763C/-1082A/-819C/-592C was associated with resistance to leprosy per se and to the development of severe form of leprosy, using either a binomial (controls vs cases, P=0.01, OR=0.58, CI=0.37–0.89) or ordinal (controls vs paucibacillary vs multibacillary, P=0.004) model. Whereas, IL-10 haplotype −3575T/-2849G/-2763C/-1082A/-819T/-592A was associated with the risk of development of severe form of leprosy (P=0.0002) in contrast to the minor risk haplotype −3575T/-2849A/-2763C in the Brazilian population. The role of IL-10 promoter SNPs in Brazilian and Indian population strongly suggests the involvement of IL-10 locus in the outcome of leprosy.     

Basal cell carcinoma and variants in genes coding for immune response, DNA repair, folate and iron metabolism

Basal cell carcinoma (BCC) is one of the most common neoplasms in the world and its incidence has been increasing worldwide in recent years. BCCs are caused by an interplay between genetic and environment factors. We conducted a case-control association study in BCC patients and controls from Sweden and Finland. Fifteen single nucleotide polymorphisms (SNPs), IL-6-174G/C, -634G/C, and -597G/A; IL-10-1082G/A and -592C/A; IL-1beta-511C/T; NBS1 exon 5 Glu185Gln; XPC exon 15 Lys939Gln; XPD exon 23 Lys751Gln; XRCC1 exon 10 Arg399Gln; XRCC3 exon 7 Thr241Met; cyclin D1 exon 4 G870A; MTHFR exon 4 Ala222Val and exon 7 Glu429Ala; HFE exon 4 C282Y were performed by Pyrosequencing and RFLP techniques. Most of the genotype distributions were in accordance with the Hardy-Weinberg equilibrium (HWE), except for IL-10-1082G/A, where cases with BCC showed a significant deviation from HWE (P = 0.04). Linkage disequilibrium was observed between the -174 and -597 alleles in the IL-6 gene in the present populations. No difference between BCC and controls appeared in any of the SNPs analyzed. Only the combined distributions of TT/AA genotypes in MTHFR exon 4 (C/T) and exon 7 (A/C) showed slight increase in BCC compared to controls (P < 0.07, OR: 1.94; 95% CI: 0.96-3.89).     

Interleukin-10 gene promoter polymorphisms and their protein production in pleural fluid in patients with tuberculosis

Associations of interleukin-10 (IL-10) gene promoter polymorphisms and pleural tuberculosis risk remain unclear. The objective of this study was to determine IL-10 gene promoter polymorphisms at -1082, -819 and -592 sites and their protein production in pleural fluid (PF) in patients with and without pleural tuberculosis. IL-10 gene promoter polymorphisms at the -1082, -819 and -592 sites were genotyped using a SNaPshot assay. Protein levels of IL-10 in PF were measured using an enzyme-linked immunosorbent assay. There were no significant differences in the genotype and allele frequencies of IL-10 gene promoter polymorphisms at position -1082 between the pleural tuberculosis and the control groups. However, the frequency of -819 T or -592 A alleles was significantly more common in patients with pleural tuberculosis than controls. The protein levels of IL-10 in PF were statistically higher in the pleural tuberculosis group than in the control group. Moreover, the polymorphisms at the -1082, -819 and -592 sites were associated with protein levels of IL-10 in PF in the pleural tuberculosis group, while in the control group, only the polymorphism at position -1082 correlated with the protein levels. These findings support the association between IL-10 promoter polymorphisms at -819 and -592 sites and their protein production with pleural tuberculosis risk.     

Immunolocalization of type X collagen in human lumbar intervertebral discs during ageing and degeneration

 Type X collagen has so far not been reported to occur in human intervertebral discs. The objective of this study was therefore to investigate the occurrence of type X collagen in human lumbar intervertebral discs during ageing and degeneration. Ninety intervertebral discs with adjacent endplates were excised in toto from individuals (0–86 years) without known spinal disease and were processed for routine decalcified histology. Appropriate slices of each disc were processed for immunohistochemistry using a type-spec ific, monoclonal antibody raised against human type X collagen. Each intervertebral disc was examined for macroscopic and histomorphological features of disc degeneration. Immunohistochemically, a positive specific type X staining was observed in the hypertrophic zone of the growth plate and only in the interstitial matrix of juvenile (<2 years) nucleus pulposus. In adult discs, type X collagen could be localized in conjunction with advanced disc degeneration and first occurred in the disc matrix (i.e., pericellular region) of a 47-year-old specimen. Positive type X staining of the disc matrix was more frequently found in senile (>70 years) discs with end stages of disc degeneration. This study provides the first evidence for the occurrence of type X collagen in human lumbar intervertebral discs and it appears that type X collagen is re-expressed in late stages of disc degeneration. Accepted: 24 April 1997     

Association of interleukin-10 gene promoter polymorphisms with susceptibility to acute pyelonephritis in children

Interleukin-10 (IL-10) is a potent inhibitor of leukocyte chemotaxis, bacterial killing in phagocytes and synthesis of pro-inflammatory cytokines and chemokines, and recent studies have suggested an important role for this immunoregulatory cytokine in the pathogenesis of urinary tract infections (UTIs). Therefore, the gene encoding IL-10 (IL10) is an attractive candidate for association studies attempting to identify susceptibility genes conferring risk of UTIs. In this case–control study, we aimed to investigate the association of single nucleotide polymorphisms (SNPs) in the promoter region of IL10 with acute pyelonephritis in the Slovak population. Polymerase chain reaction with sequence-specific primers was used to analyse IL10 ?1082A/G (rs1800896), ?819C/T (rs1800871) and ?592C/A (rs1800872) SNPs in 147 children with acute pyelonephritis and 215 healthy controls. Comparison of patients with healthy controls using the logistic regression analysis revealed significantly increased risk of developing recurrent attacks of acute pyelonephritis for ?1082 G allele in a dominant genetic model GG (GG + AG vs. AA, P?=?0.019, odds ratio (OR)?=?2.26). A similar tendency was also found when the recurrent acute pyelonephritis subgroup was compared to episodic pyelonephritis cases (GG + AG vs. AA, P?=?0.009, OR?=?3.38). In conclusion, our results suggest that IL10 ?1082 A/G SNP is a susceptibility factor for development of recurrent attacks of acute pyelonephritis.     

退行性腰椎滑脱临近节段椎间盘退变和关节突关节角度相关研究

目的:探讨退行性腰椎滑脱(DLS)临近节段椎间盘退变程度和关节突关节角度之间的关系。方法:选取我院2012年6月至2016年6月收治的120例DLS患者作为DLS组,另外选取来我院接受体检的健康者120例作为对照组,选择CT进行关节突关节角和腰椎滑脱度的测量,使用MRI的T2像对椎间盘进行Pfirrmann退变分级。结果:DLS组的各节段关节突关节角度均小于对照组(P0.05);DLS组不同滑脱程度的L2/3、L3/4、L5/S1节段关节突关节角度的比较,差异无统计学意义(P0.05);DLS组L2/3、L3/4、L5/S1节段不同椎间盘退变等级间的滑脱程度无显著性差异(P0.05)。L2/3和L3/4节段不同椎间盘退变程度间关节突关节角度差无显著性差异(P0.05),L5/S1节段不同椎间盘退变程度间关节突关节角度差有统计学差异(P0.05)。结论:退行性腰椎滑脱临近节段关节突关节角度明显小于正常人,且临近节段关节突关节的角度并未随着腰椎滑脱程度的加重而改变,退行性腰椎滑脱患者滑脱临近节段椎间盘退变与关节突关节的矢状化程度无关,但L5/S1关节突关节角度不对称性会影响到同节段椎间盘退变程度。     

IL-1b基因单核苷酸多态性与腰椎间盘疾病的相关性

为研究汉族人白细胞介素-1b（IL-1b）基因 ^-511T>C 和 ⁺³⁹⁵⁴C>T位点单核苷酸多态性与腰椎间盘疾病的关系, 采用聚合酶链反应技术, 扩增 81 例腰椎间盘疾病患者和 101 例正常对照者中分别包含IL-1b 基因 ^-511T>C 和 ⁺³⁹⁵⁴C>T 位点的片段, 酶切法鉴定 IL-1b基因 ^-511T>C和 ⁺³⁹⁵⁴C>T 位点单核苷酸多态性情况, 比较两组中基因多态性与腰椎间盘疾病的关系。同时, 利用 MRI 检测两组腰椎间盘退变的情况, 并分析其中小于45岁者IL-1b基因多态性与腰椎间盘退变严重程度的关系。结果显示, 腰椎间盘疾病病例组及对照组中均存在IL-1b基因 ^-511T>C 和 ⁺³⁹⁵⁴C>T 位点单核苷酸多态性。IL-1b 基因 ^-511T>C 位点 TT、TC 和 CC基因型, T、C 基因型差别与腰椎间盘疾病有关（P<0.01）, 与腰椎间盘退变严重程度无关(P>0.05), 但IL-1b基因 ⁺³⁹⁵⁴C>T 位点单核苷酸多态性与腰椎间盘退变严重程度及腰椎间盘疾病均无关(P>0.05)。表明在汉族人中, 存在 IL-1b 基因 ^-511T>C 和 ⁺³⁹⁵⁴C>T 位点单核苷酸多态性, 但仅 ^-511T>C 位点单核苷酸多态性与腰椎间盘疾病有关。     

IL-12 and IL-10 polymorphisms and their effects on cytokine production

Interleukin (IL)-12 is an inducer of differentiation of T helper (Th) cells towards Th1, whereas IL-10 is mainly an anti-inflammatory cytokine inhibiting Th1 functions. Single nucleotide polymorphisms (SNPs) in the regulatory sequences of genes are presumed to be associated with the differential production of cytokines. One IL12B 3'untranslated region (UTR) and five of IL10 gene promoter region SNPs were screened in 152 individuals by genotyping. IL-10 and IL-12 secretion of lipopolysaccharide (LPS), purified protein derivative (PPD) and Staphylococcus aureus Cowan strain I (SAC) stimulated peripheral blood mononuclear cells (PBMCs) was determined. The frequencies of the less frequent IL12B +16974 C, IL10 -2763 A -3575 A, -1082 G, -819 T and -592 A alleles were 27.4, 32.2, 25.9, 14.8, 9.3 and 8.6%, respectively. Individuals CC homozygous at IL12B 3'UTR had significantly higher IL-12 secretion levels from LPS and PPD stimulated PBMCs than AC heterozygotes (P = 0.03 and P = 0.02) or AA homozygotes (P = 0.02 and P = 0.05, respectively). IL10 -2763 and -3575 SNPs did not show any effect on in vitro secretion levels, whereas the association of proximal promoter -1082 SNP with IL-10 production is confirmed. IL10 proximal and distal promoter SNP distribution with estimated haplotype variations has implicated considerable similarities with the Caucasian populations in Turkey.     

Interleukin-10 gene polymorphisms and chronic/aggressive periodontitis susceptibility: A meta-analysis based on 14 case-control studies

Interleukin-10 (IL-10) has been described as an anti-inflammatory cytokine and IL-10 gene polymorphisms was associated with altered interleukin-10 levels, therefore, we aimed to conduct a meta-analysis assessing the association of IL-10 genetic polymorphisms with the risk of both chronic periodontitis (CP) and aggressive periodontitis (AgP). Electronic databases were acquired from PubMed, Embase, the Sinomed and WANFANG. Fourteen studies with 1438 patients and 1303 control subjects investigated the association of the three single-nucleotide polymorphisms (SNPs) of IL-10 (-1082A>G, -819C>T, -592C>A) and chronic/aggressive periodontitis risk were brought into this study. We found that there was no association between IL-10 -1082 gene polymorphism and periodontitis risk (either CP or AgP), even when we separately investigated sub-group analysis among Caucasians. The -819 polymorphism seemed to be a genetic risk factor to CP among Caucasians (T allele vs. C allele: OR=1.55, 95%CI=1.07-2.24; CT vs. CC: OR=1.64, 95%CI=1.00-2.67). When excluding one study deviated from HWE, the results showed that the T allele carriers had a significantly risk of CP in overall population (T allele vs. C allele: OR=1.23, 95%CI=1.03-1.48). Furthermore, the results of this meta-analysis showed that -592 polymorphism was associated with a significantly increased risk of CP (A allele vs. C allele: OR=1.38, 95%CI=1.04-1.85; AA vs. CA+CC: OR=1.39, 95%CI=1.05-1.85 for overall analysis; A allele vs. C allele: OR=1.97, 95%CI=1.36-3.86; AA vs. CC: OR=3.70, 95%CI=1.32-10.39; CA vs. CC: OR=2.22, 95%CI=1.36-3.64, AA+CA vs. CC: OR=2.35, 95%CI=1.46-3.79 for Caucasian descent analysis). This meta-analysis suggested that IL-10 -819 and -592 gene polymorphisms were associated with CP, especially among Caucasians. Further research is needed to assess possible gene-gene or gene-environment-lifestyle interactions on periodontal disease..     

Alleles and haplotypes of the interleukin 10 gene polymorphisms are associated with risk of developing acute coronary syndrome in Mexican patients

Inflammation plays an important role in the pathogenesis of atherosclerosis and acute coronary syndromes (ACS). Interleukin-10 (IL-10) is a potent anti-inflammatory cytokine that mediates the inflammatory process. The objective of the present study was to evaluate the role of IL-10 gene polymorphisms as susceptibility markers for ACS in Mexican patients. IL-10 promoter polymorphisms (positions -1082, -819, and -592) were analyzed by 5' exonuclease TaqMan genotyping assays in 389 ACS patients and 302 healthy controls. ACS patients showed increased frequencies of IL-10-592 C allele and CC genotype when compared to healthy controls (pC=0.0006, OR=1.48 and pC=0.022, OR=1.56, respectively), whereas the frequencies of the A allele and AA genotype were decreased in patients (pC=0.0006, OR=0.68 and pC=0.006, OR=0.57, respectively). When the distribution of IL-10-592 genotypes was analyzed separately in women and men (patients and healthy controls), a different distribution of alleles and genotypes was observed only in the group of men. In this case, increased frequency of C allele (pC=0.004, OR=1.46) and decreased frequencies of A allele (pC=0.004, OR=0.68) and AA genotype (pC=0.023, OR=0.56) were observed in the group of patients when compared to healthy controls. Multiple logistic analyses by gender showed that male individuals with IL-10-592CC+AC genotypes had 3.54-fold increased risk of developing ACS than individuals with AA genotype (p<0.001). The analysis of linkage disequilibrium showed one (ACC) increased haplotype in patients as compared to healthy controls. The results suggest that IL-10 gene polymorphisms could be involved in the risk of developing ACS in the Mexican population.     

白细胞介素-10基因启动子多态性与子宫内膜异位症遗传易感性的相关性

为了探讨中国汉族妇女白细胞介素-10(IL-10)启动子的基因多态性与子宫内膜异位症(EMs)遗传易感性的关系, 文章应用扩增阻滞突变系统-聚合酶链反应(ARMS-PCR)结合DNA测序法, 以及聚合酶链反应-限制性片段长度多态性(PCR-RFLP)分析方法, 对119例不同期别的EMs组患者和120例随机抽取的汉族妇女进行了IL-10-1082G/A、-819T/C和-592A/C的基因多态性分析。结果表明: EMs组-1082等位基因频率和基因型分布与对照组比较, 差异无显著(P>0.05), 而EMs组-819C 或-592C、-819CC和TC或-592CC和AC的等位基因或基因型频率均显著高于对照组(P<0.05); 另外, Ⅲ-Ⅳ期EMs患者-819C 或-592C、-819CC和TC或-592CC和AC的等位基因或基因型频率又显著高于Ⅰ-Ⅱ期EMs患者和对照组(P<0.01)。这表明IL-10-819T/C和-592A/C位点多态性与中国汉族妇女EMs发病的易感性有一定关系。     

Genome-wide association study in Dachshund: identification of a major locus affecting intervertebral disc calcification

Intervertebral disc calcification and herniation commonly affects Dachshund where the predisposition is caused by an early onset degenerative process resulting in disc calcification. A continuous spectrum of disc degeneration is seen within and among dog breeds, suggesting a multifactorial etiology. The number of calcified discs at 2 years of age determined by a radiographic evaluation is a good indicator of the severity of disc degeneration and thus serves as a measure for the risk of developing intervertebral disc herniation. The aim of the study was to identify genetic variants associated with intervertebral disc calcification in Dachshund through a genome-wide association (GWA) study. Based on thorough radiographic examinations, 48 cases with ≥ 6 disc calcifications or surgically treated for disc herniation and 46 controls with 0-1 disc calcifications were identified. GWA using the Illumina CanineHD BeadChip identified a locus on chromosome 12 from 36.8 to 38.6 Mb with 36 markers reaching genome-wide significance (P(genome) = 0.00001-0.026). This study suggests that a major locus on chromosome 12 harbors genetic variations affecting the development of intervertebral disc calcification in Dachshund.     

IL-10 Gene Polymorphisms and Susceptibility to Systemic Lupus Erythematosus: A Meta-Analysis

Background

A number of observational studies have been conducted to investigate the association of the IL-10 gene polymorphisms with systemic lupus erythematosus (SLE) susceptibility. However, their results are conflicting.

Method

We searched published case-control studies on the IL-10 polymorphisms and SLE in PubMed, EMBASE and Chinese Biomedical Literature Database. A meta-analysis was conducted using a fixed-effect or random-effect model based on between-study heterogeneity.

Results

A total of 42 studies with 7948 cases and 11866 controls were included in this meta-analysis. Among Caucasians, the CA27 allele of the IL10.G microsatellites (OR 2.38, 95% CI 1.01–5.62), the G allele of the IL-10 -1082G/A polymorphism (G vs. A: OR 1.21, 95% CI 1.02–1.44; GG vs. AA: OR 1.45, 95% CI 1.16–1.82; GG+GA vs. AA: OR 1.16, 95% CI 1.03–1.29) and its associated haplotype -1082G/−819C/−592C (OR 1.25, 95% CI 1.10–1.42) were associated with increased SLE susceptibility without or with unimportant between-study heterogeneity. Removing studies deviating from Hardy-Weinberg equilibrium (HWE) hardly changed these results. Among Asians, the CA21 allele of the IL-10.G microsatellites (OR 1.28, 95% CI 1.02–1.60) and the -1082G/−819C/−592C haplotype (OR 1.24, 95% CI 1.00–1.53) were associated with increased SLE susceptibility, but with substantial between-study heterogeneity or sensitive to HWE status. Removing studies deviating from HWE also produced statistically significant associations of the IL-10 -1082G/A (GG vs. AA: OR 3.21, 95% CI 1.24–8.28; GG vs. AA+GA: OR 2.85, 95% CI 1.19–6.79) and -592C/A polymorphisms (CC+CA vs. AA: OR 0.69, 95% CI 0.51–0.94) with SLE among Asians.

Conclusion

This meta-analysis showed that the IL10.G microsatellites, the IL-10 -1082G/A and -592C/A polymorphisms and the haplotype -1082G/−819C/−592C are associated with SLE susceptibility. Besides, this is the first time to report an association between the CA27 allele of the IL-10.G microsatellites and SLE among Caucasians. Further studies are needed to confirm these findings.     

Polymorphism in the Hypoxia-Inducible Factor 1alpha Gene May Confer Susceptibility to LDD in Chinese Cohort

Objective

This study aimed to investigate whether or not hypoxia-inducible factor-1α (HIF-1α) gene variants are associated with the susceptibility and clinical characteristics of lumbar disc degeneration (LDD).

Methods

We examined 320 patients with LDD and 447 gender- and age-matched control subjects. We also determined the HIF-1α gene variants, including C1772T (P582S) and G1790A (A588T) polymorphisms.

Results

Significant differences were observed in allelic and genotypic distributions of 1790 A > G polymorphisms between LDD cases and control subjects. Logistic regression revealed that 1790 AA genotypes indicated a protective effect against the development of LDD. The HIF-1α 1790 A > G polymorphisms also affected the severity of LDD as evaluated based on the modified Japanese Orthopedic Association (mJOA) scores. The 1790 AA genotype carriers exhibited significantly lower mJOA scores than AG and GG carriers. C1772T did not show any association with the risk and severity of LDD.

Conclusion

Our study suggested that HIF-1α 1790 A > G polymorphisms may be used as a molecular marker to determine the susceptibility and severity of LDD.     

Combination of low producer AA-genotypes in IFN-γ and IL-10 genes makes a high risk genetic variant for HIV disease progression

Rate of HIV disease progression varies considerably among individuals, host genetic makeup be one of the possible reasons. We aimed to determine association of functional single nucleotide polymorphism (SNPs), (−179G/T and +874T/A) in IFN-γ and (−1082A/G, −819C/T and −592C/A) in IL-10 genes, with the rate of disease progression or susceptibility to HIV infection. Therapy naïve HIV infected individuals from North India, categorized as slow progressors or fast progressors and HIV exposed seronegative individuals were recruited for this study. Genotyping results revealed significantly higher frequencies of low producer AA genotype at +874T/A in IFN-γ gene and −592C/A position in IL-10 gene in FPs (p < 0.002). Multifactor dimensional reduction (MDR) analysis revealed this to be a high risk combination for faster disease progression in HIV-1 infected individuals. Low producer AA genotype carriers at +874T/A in IFN-γ gene produced significantly low amounts of cellular IFN-γ. Low producing haplotype ‘ATA’ at −1082, −819 and −592 loci in IL-10 gene was significantly over-represented in FPs as compared to SPs (p < 0.01) and these individuals showed poor response to therapy in terms of CD4 count gains after one year of ART, compared to high producing haplotype (GCC) carriers. Thus, a combination of genetic variations in IFN-γ and IL-10 cytokine genes in a single host associate with HIV disease progression and may help clinicians to better manage the HIV disease if known earlier.     

Serum CXCL12/SDF-1 level is positively related with lumbar intervertebral disc degeneration and clinical severity

This study aimed to examine whether stromal cell-derived factor-1 (SDF-1) or C-X-C chemokine ligand 12 (CXCL12) participates in the development of lumbar disc degeneration, as implicated earlier by the level of CXCL12 correlating with this disease. It enrolled 145 patients with symptomatic lumbar intervertebral disc degeneration (IDD) and 130 asymptomatic healthy controls with no indication of IDD. Radiological assessment of the IDD patients was targeted at the lumbar vertebra region, based on Pfirrmann grade. Degeneration of the multifidus and psoas major muscles was evaluated using Goutallier classification. Visual Analogue Scale (VAS) and Oswestry Disability Index (ODI) scores were obtained for assessing the severity of manifestation. The levels of serum CXCL12, IL-6 and TNF-α were determined by ROC curve analysis, resulting in their prognostic value for Pfirrmann grading. Higher levels of serum CXCL12 were found in patients with IDD than in asymptomatic individuals, and were positively related to the Pfirrmann grade as well as multifidus muscle degeneration. Furthermore, serum CXCL12 concentration showed a significant correlation with the VAS and ODI scores. In addition, elevated serum CXCL12 levels were related to serum levels of TNF-α and IL-6. The ROC curve analysis implicated that CXCL12 could function as a biomarker of the early-mediate phase of IDD development. In summary, the serum CXCL12/SDF-1 level is positively related with lumbar IDD and its clinical severity.     

Comprehensive analysis of genetic polymorphisms in the interleukin-10 promoter: implications for immune regulation in specific ethnic populations

The association of interleukin-10 (IL-10) promoter single-nucleotide polymorphisms (SNPs) as risk factors for certain inflammatory diseases, viral infections, cancers, and transplant rejection have been the subject of recent studies. The SNPs -1082 G --> A, -819 C --> T, and -592 C --> A, which have been associated with differential IL-10 production, are strongly linked with ethnicity. In this study, we determined the ethnic distribution of IL-10 promoter SNPs and their haplotype rates among Hispanics, African Americans, and Caucasians from Texas and Ashkenazi Jews from New York. Significant differences in prevalence rates of IL-10 SNPs (and their haplotype distribution) were found. African Americans and Hispanics have a lower rate of putative high-producer SNPs and a higher rate of low IL-10 producers when compared to Caucasians or Ashkenazi Jews. No statistically significant differences in allelic frequencies and haplotype rates were observed between Caucasians and Ashkenazi Jews. This study provides critical new information on the ethnic distribution of IL-10 promoter SNPs in a regional U. S. population and is the first to analyze the rate of SNPs in an unstudied ethnic population, Ashkenazi Jews. Knowledge of IL-10 promoter polymorphisms may prove useful in prediction of immunization responses, disease severity, and in the intelligent design of customized immunotherapy.     

Interleukin-8 and -10 gene polymorphisms in irritable bowel syndrome

Irritable bowel syndrome (IBS) is one of the most common gastrointestinal diagnoses seen by primary care providers and gastroenterologists. Proinflammatory cytokines interleukin (IL)-6 and IL-8 have been found increased in IBS patients. Cytokine gene single nucleotide polymorphisms (SNPs) of IL-8 and IL-10 have not been assessed in Mexican IBS patients. DNA was extracted from peripheral blood leucocytes of 45 IBS unrelated patients and 137 controls. Allele, genotype, and haplotype frequencies were determined by analyzing SNPs of IL-8 and IL-10 genes. IL-8 + 396 G allele (P = 0.02), IL-8 + 396(G/G) and IL-8 + 781(C/T) genotypes (P < 0.001), IL-10 - 1082A allele and IL-10 - 1082(A/A) genotype (P < 0.001) were significantly increased in the IBS group. Haplotypes IL-8 ATCC (P = 0.03) and IL-10 ACC (P < 0.001) were associated with susceptibility to develop IBS. An association of certain polymorphisms of IL-8 and IL-10 in IBS patients compared to controls was demonstrated, suggesting a role of these cytokine SNPs in the pathophysiology of IBS.