TLR3 polymorphisms are associated with virologic response to hepatitis C virus (HCV) treatment in HIV/HCV coinfected patients

BackgroundToll-like receptor-3 (TLR3) is a cellular receptor that may recognize double-stranded RNA (dsRNA) from viruses, resulting in production of proinflammatory cytokines and interferons, which are important for the adaptive immune response.ObjectivesTo analyze the association between Toll-like receptor-3 (TLR3) polymorphisms (rs3775291 and rs13126816) and virologic response to pegylated interferon-alpha plus ribavirin (pegIFNα/RBV) therapy in HIV/HCV coinfected patients.Study designWe performed a retrospective study in 321 naïve patients treated with pegIFNα/RBV. Genotyping was performed by using the GoldenGate^® assay with VeraCode^®. The outcome variables were early virologic response (EVR) and sustained virologic response (SVR).ResultsIn a multivariate analysis, rs3775291 A allele decreased the likelihood of achieving EVR (aOR = 0.20; p = 0.018) and SVR (aOR = 0.38; p = 0.024). Regarding rs13126816, the percentage of EVR decreased with each minor A allele (p = 0.034) in HCV-GT2/3 patients, although no significant association was obtained in the multivariate analysis (p = 0.076). Regarding TLR3 haplotypes (comprised of rs3775291 and rs13126816), GT2/3 patients with AA haplotype had decreased odds of achieving EVR (p = 0.030), whereas GG haplotype increased the likelihood (p = 0.018). Regarding SVR, GG haplotype carriers had increased odds of achieving SVR (p = 0.019, p = 0.043 and p = 0.070 for all, GT2/3 and GT1/4 patients, respectively). Besides, GT1/4 patients with GA haplotype had lower odds of achieving SVR (p = 0.039).ConclusionsOur study shows the first evidence that two TLR3 polymorphisms (rs3775291 and rs13126816) seem to be related to the HCV therapy response in HCV/HIV coinfected patients.     

Interleukin-18 promoter -607 C/A and -137 G/C polymorphisms and susceptibility to type 1 diabetes: A meta-analysis

ObjectiveThe aim of this study was to determine whether the functional interleukin-18 (IL-18) promoter -607 C/A (rs1946518) and -137 G/C (rs187238) polymorphisms are associated with susceptibility to type 1 diabetes (TID).MethodsA meta-analysis was conducted to assess the associations between the IL-18 -607 C/A and -137 G/C polymorphisms and T1D in overall and by ethnic group.ResultsA total of 6075 cases and 5744 controls from ten studies were considered in this meta-analysis. In all study subjects, the meta-analysis showed no association between T1D and the IL-18 -607 C allele (OR = 1.083, 95% CI = 0.930–1.260, p = 0.307). However, stratification by ethnicity indicated an association between the IL-18 -607 C allele and T1D in Asians (OR = 1.506, 95% CI = 1.172–1.936, p = 0.001), but not in Europeans (OR = 0.988, 95% CI = 0.808–1.209, p = 0.907). Analysis using recessive and dominant models and homozygote contrast showed the same -607 C allele pattern in Asians and Europeans. Meta-analysis of the IL-18 -137 G/C polymorphism showed no association between T1D and the IL-18 -137 G allele in all study subjects (OR = 1.066, 95% CI = 0.926–1.2289, p = 0.375). Stratification by ethnicity indicated no association between the IL-18 -137 G allele and T1D in Europeans and Asians (OR = 1.021, 95% CI = 0.961–1.085, p = 0.504; OR = 0.851, 95% CI = 0.5821–1.245, p = 0.406).ConclusionsOur meta-analysis demonstrates that the IL-18 -607 C/A polymorphism may be associated with susceptibility to T1D in Asians, but not in Europeans.     

Role of ITPA and SLC28A2 genes in the prediction of anaemia associated with protease inhibitor plus ribavirin and peginterferon in hepatitis C treatment

BackgroundAnaemia is a common side-effect of ribavirin (RBV) use that overwhelms management of hepatitis C when protease inhibitors are added.AimTo assess the pharmacogenomic impact of candidate genes SLC28A2, SLC28A3 and ITPA on anaemia in patients receiving triple therapy.MethodsPatients (n = 161) with chronic hepatitis C genotype 1 treated with telaprevir (n = 95) or boceprevir (n = 66) were included. Using RT-PCR we genotyped ITPA (rs1127354, rs7270101) and SLC28A3 (rs56350726, rs10868138) and SLC28A2 (rs11854484). Clinically significant anaemia (CSA) was diagnosed when at least one of the following criteria was observed: (a) haemoglobin <8.5 g/dL during treatment; (b) blood transfusion required; (c) erythropoietin administered.ResultsCSA occurred in 44% (69/157) of patients and was associated with SLC28A2 rs11854484 [CC/CT genotypes: 33% (26/78) vs. TT genotype: 56% (36/64); p = 0.006]. Further, the needed for blood transfusion was related to genotype [CC: 0% (0/18) vs. CT: 13% (8/61) vs. TT: 27% (17/64); p = 0.016]. Similarly, ITPA rs1127354 genotypes [AA/AC: 19% (3/16) vs. CC: 45% (61/135; p = 0.060] were linked to CSA. In multivariate analysis, SLC28A2 rs11854484 TT genotype (OR:2.33;95%CI:1.10–4.95; p = 0.027), female sex (OR:2.54;95% CI:1.13–5.71;p = 0.024) and Hb drop at week 4) OR: 1.36; 95CI%: 1.11–1.67; p = 0.003) were independently associated with CSA. Similarly, ITPA rs1127354 genotypes [AA/AC: 16% (3/19) vs. CC: 63% (85/134); p = 0.0001] and ITPA rs6051702 genotypes [CC/CA: 46% (26/57) vs. CC: 65% (60/93); p = 0.023] were related to Hb drop of >3g/dL at week 4.ConclusionsIn patients receiving first generation protease inhibitors, genotype SLC28A2 rs11854484 predicts CSA, and helps to identify a subgroup of patients with better tolerance of triple therapy.     

Evidence of association of interleukin-23 receptor gene polymorphisms with Egyptian rheumatoid arthritis patients

BackgroundThe identification of additional genetic risk factor is an on-going process that will aid in the understanding of rheumatoid arthritis (RA) aetiology. A genome-wide association scan in Crohn’s (CD) disease highlighted the interleukin-23 receptor (IL23R) gene as a susceptibility factor. Since the IL-23/IL-17 pathway is known to associate with other autoimmune disease, including rheumatoid arthritis and systemic sclerosis, we hypothesised that IL23R could be a shared susceptibility gene. The rare allele of IL23R single nucleotide polymorphism (SNP) rs11209026 (Arg381Gln) confers strong protection against CD. Our aim was to analyse IL23R SNP (rs11209026, rs2201841, and rs10889677) and to detect its association with RA in Egyptian patients.MethodsA group of Egyptian patients with RA (n = 120) and apparently healthy persons as controls (n = 120) was genotyped for rs11209026, rs2201841 and rs10889677 by real time/polymerase chain reaction (real-time/PCR) for the first SNP and restriction fragment length polymorphism/PCR (RFLP/PCR) in the last two SNPs.ResultsOur data emphasise that the AA genotype of rs11209026 (Arg381Gln) was significantly associated with RA patients compared to the controls (P value = 0.001).We did not find any significant association between either rs2201841 or rs10889677 and the development of rheumatoid arthritis (P value = 1.000 & 0.562 respectively).ConclusionOur results suggest that IL23 receptor AA genotype variant of rs11209026 would contribute to RA aetiology; consequently, it might be a genetic marker for RA. We need to address the subgroup of patients who will benefit from the selective suppression of the IL23 signalling which would represent new perspectives toward a personalized therapy of RA patients by further studies.     

Association of IL-17A and IL-17F polymorphisms with gastric cancer risk in Asians: A meta-analysis

Increasing number of studies focused on the association of IL-17A rs2275913 and IL-17F rs763780 polymorphisms with gastric cancer (GC) risk. However, the results were inconsistent. To elucidate the exact association, we performed the present meta-analysis. Databases including PubMed, Web of knowledge and Chinese National Knowledge Infrastructure (CNKI) were systematically searched for potentially eligible literatures. Odds ratios (OR) and their 95% confidence interval (CI) were used to evaluate the strength of association. Eight studies for IL-17A rs2275913 (3345 cases and 4427 controls) and five studies for IL-17F rs763780 (1784 cases and 2592 controls) were finally included. The results indicated that individuals with AA genotype of IL-17A rs2275913 polymorphism were associated with increased GC risk compared with wild-type GG (OR = 1.61, 95% CI = 1.17–2.23, P = 0.004); A allele was significantly associated with increased GC risk compared with G allele (OR = 1.22, 95% CI = 1.06–1.41, P = 0.007). IL-17F rs763780 polymorphism was also significantly associated with increased GC risk (CC vs. CT: OR = 1.40, 95% CI = 1.04–1.88, P = 0.025; CT vs. TT: OR = 1.35, 95% CI = 1.16–1.58, P < 0.001; C allele vs. T allele: OR = 1.30, 95% CI = 1.15–1.47, P < 0.001). In summary, IL-17A rs2275913 A/G polymorphism and IL-17F rs763780 C/T polymorphism might be associated with increased GC risk in Asians. Further large-scale studies are still required to confirm the results of this meta-analysis.     

Association between IFNL4 rs368234815 polymorphism and sustained virological response in chronic hepatitis C patients undergoing PEGylated interferon/ribavirin therapy: A meta-analysis

Background and aimsMany studies have been published on the association between IFNL4 rs368234815 single-nucleotide polymorphism (SNP) and sustained virological response (SVR) in chronic hepatitis C (CHC) patients undergoing treatment with PEGylated interferon (PEG-IFN) plus ribavirin (RBV). Because of the variable and sometimes inconsistent results, we performed a meta-analysis to estimate the association between these factors.MethodsWe conducted a search of the literature published prior to July 1, 2014. The pooled results were analyzed as the odds ratios (ORs) and corresponding 95% confidence intervals (CIs) using random-effect model.ResultsThe pooled results revealed that the rs368234815 TT/TT genotype was significantly correlated with SVR in HCV-1/4-infected Caucasian patients (OR = 4.65, 95% CI = 3.36–6.42, P < 0.00001) but not in HCV-2/3-infected Caucasian patients (OR = 1.44, 95% CI: 0.89–2.33, P = 0.13). Conversely, the rs368234815 ΔG/ΔG genotype was significantly linked to treatment failure in Caucasian patients (OR = 0.49, 95% CI: 0.38–0.64, P < 0.00001), regardless of the HCV genotype.ConclusionThe results of the meta-analysis suggest that IFNL4 rs368234815 polymorphism may be a predictor of SVR in Caucasian HCV-1/4-infected patients.     

The association of PTPN22 (rs2476601) and IL2RA (rs11594656) polymorphisms with T1D in Egyptian children

BackgroundType 1 diabetes mellitus (T1D) is a T cell-mediated autoimmune disease characterized by the destruction of pancreatic β cells. PTPN22 and IL2RA polymorphisms have been found to be associated with several autoimmune diseases including T1D.AimsWe aimed to elucidate the role of PTPN22 and IL2RA polymorphisms in predisposition of T1D in Egyptian children.MethodsWe studied 150 children and adolescents with T1D and 165 healthy controls. The PTPN22 (rs2476601) and IL2RA (rs11594656) polymorphisms were genotyped using polymerase chain reaction.ResultsWe found that carriers of the T allele of PTPN22 were significantly more likely to develop T1D (OR = 2.2, 95% CI = 1.2–4, P = 0.01). Also, the carrier of TT genotype and T allele of IL2RA more likely to develop T1D (OR = 2.8, 1.4, respectively, P = 0.03). There was a statistically significant association between T allele of PTPN22 gene and females ⩽10 years old at the onset of diabetes (OR = 4, 95% CI = 1.2–13.4, P = 0.019).ConclusionThis study suggests a possible association between the T allele of PTPN22 gene and TT genotype of IL2RA with T1D in studied Egyptian children, especially, females with early onset diabetes who carried the 1858T allele.     

Association study of rs924080 and rs11209032 polymorphisms of IL23R-IL12RB2 in a Northern Chinese Han population with Behcet’s disease

ObjectivesTwo genome-wide association studies (GWAS) have identified the IL-23 receptor- IL-12 receptor β2 (IL23R-IL12RB2) as the susceptibility genetic region in Turkish and Japanese population with Behçet’s disease (BD). We investigated the association of this region with BD in a Northern Chinese Han population.MethodsA total of 407 patients with BD and 421 healthy controls were genotyped for single nucleotide polymorphisms (SNPs) rs924080 and rs11209032 using the Sequenom MassArray system.ResultsStatistically significant associations with BD were detected at two SNPs namely, rs924080 and rs11209032, both, by allele analysis (OR = 1.58, 95% CI = 1.25–2.00, P_c = 2.52 × 10⁻⁴, and OR = 1.45, 95% CI = 1.19–1.76, P_c = 3.46 × 10⁻⁴, respectively), and genotype analysis (P_c = 1.22 × 10⁻³ and P_c = 1.77 × 10⁻³, respectively). Significant differences were observed in the genotype frequency distribution for these SNPs under the additive, dominant and recessive models (all P_c < 0.05). The haplotypes (AT and GC) formed by the two SNPs were associated with BD (all permutation P < 0.05). A meta-analysis also appeared to support the association of the two SNPs with BD.ConclusionSNPs (rs924080 and rs11209032) of the IL23R-IL12RB2 region were found to be associated with BD in a Northern Chinese Han population.     

A haplotype of the CYP4F2 gene associated with myocardial infarction in Japanese men

This study assessed associations between the CYP4F2 gene and myocardial infarction (MI), using a haplotype-based case-control study of 234 MI patients and 248 controls genotyped for 5 single-nucleotide polymorphisms (rs3093105, rs3093135, rs1558139, rs2108622, rs3093200). For men, G allele frequency of rs2108622 and frequency of the T-C-G haplotype were significantly higher, and frequency of the T-C-A haplotype was significantly lower for MI patients than for controls (P = 0.006, P = 0.001 and P = 0.002, respectively).     

CD38 gene polymorphisms and genetic predisposition to multiple myeloma

Single nucleotide polymorphisms (SNPs) of adhesion and signaling genes may influence the etiopathogenesis of multiple myeloma (MM). CD38 molecule and its ligand CD31 are expressed and interact in malignant plasma cells and MM microenvironment. In this study we evaluated allele frequencies and distribution of two potentially functional CD38 SNPs, intronic rs6449182 (184C>G) and missense rs1800561 (418C>T, Arg¹⁴⁰Trp) in 175 Caucasian patients with MM and 207 healthy blood donors. The carriers of variant G allele of the rs6449182 SNPs were found to have significantly elevated risk of MM as compared to non-carriers; odds ratio = 5.69 (95% confidence interval = 3.7–8.7), p < 0.0001. In contrast, rs1800561 SNP minor T allele was detected at very low and comparable frequencies in patients and controls groups. In conclusion, our data suggest that inherited genetic variation in CD38 gene may impact on the risk of MM development.     

PLA2G2A polymorphisms are associated with metabolic syndrome and type 2 diabetes mellitus. Results from the genetics of atherosclerotic disease Mexican study

The secretory phospholipase A₂ II A (sPLA₂-IIA) encoded by PLA2G2A gene hydrolyzes phospholipids liberating free fatty acids (FFAs) and lysophospholipids. If lipolysis exceeds lipogenesis, the free fatty acids undergo a continuous release into circulation. A sustained excessive increase in this release contributes to metabolic disease. The aim of the present study was to evaluate the role of PLA2G2A gene polymorphisms as susceptibility markers for metabolic syndrome (MetS) and type 2 diabetes mellitus (T2DM) in Mexican population. Three PLA2G2A gene polymorphisms (rs876018, rs3753827 and rs11573156) were genotyped by 5′ exonuclease TaqMan assays in a group of 338 patients with T2DM, 460 individuals with MetS and 366 healthy controls. Under codominant 1 (codom1), dominant (dom) and additive (add) models adjusted by age, gender, body mass index (BMI), smoking habit, and hypertension, the rs876018 T allele was associated with increased risk of MetS [Odds Ratio (OR) = 1.66, P_codom1 = 0.005; OR = 1.67, P_dom = 0.003; OR = 1.49, P_add = 0.005] as compared to controls. On the other hand, under several models adjusted by the same variables, the rs3753827 A (OR = 1.52, P_codom1 = 0.039 and OR = 1.49, P_dom = 0.039) and rs11573156C alleles (OR = 6.46, P_codom1 = 0.013; OR = 6.70, P_codom2 = 0.009; OR = 6.65, P_dom = 0.009) were associated with increased risk of T2DM when compared with controls. In addition, the rs876018 T allele was associated with hypercholesterolemia (P_dom = 0.017, P_add = 0.009) and risk of subclinical atherosclerosis (SA) (P_dom = 0.041) in MetS when compared with controls. Also, this allele was associated with SA in T2DM patients (P_dom = 0.007). The TAG haplotype was significantly associated with increased risk of MetS (OR = 1.54, P = 0.006). Results suggest that PLA2G2A polymorphisms are involved in the risk of developing MetS and T2D and are associated with SA in this group of patients.     

Association of inhibin α gene promoter polymorphisms with risk of idiopathic primary ovarian insufficiency in Korean women

ObjectiveThe aim of this study was to investigate whether two polymorphisms in the promoter region of inhibin alpha (INHA) are associated with risk of idiopathic primary ovarian insufficiency (POI) in Korean women, which is a controversial topic.Study designWe genotyped the INHA polymorphisms c.-16C > T (rs35118453) and c.-124A > G (rs11893842) of 136 POI patients and 225 controls in Korean women by polymerase chain reaction and restriction fragment length polymorphism analysis. We then compared differences in genotype and allele frequencies (AF) of the polymorphisms between the two groups to determine odds ratios (OR) and 95% confidence intervals (CI) as measures of the strength of association between genotype and POI.ResultsThere were no significant differences in genotype or AF of the polymorphisms between the POI patients and controls. Haplotype analysis revealed that the T–G haplotype of the two variant alleles was more frequent in POI patients than in the controls (OR = 1.630, 95% CI = 1.081–2.457). Combination genotype analysis showed that the CT + TT/GG genotype frequency was higher in POI patients than in the controls (OR = 2.414, 95% CI = 1.190–4.895).ConclusionsWe provide evidence to suggest that when the two variant alleles are combined, the c.-16C > T and c.-124A > G polymorphisms are associated with increased POI risk in Korean women. We postulate that interactions between the INHA polymorphisms may affect POI risk.     

Genetic variation in Micro-RNA genes of host genome affects clinical manifestation of symptomatic Human Cytomegalovirus infection

BackgroundMicro-RNAs are implicated in various physiological and pathologic processes. In this study, we tested whether Micro-RNA gene variants of host-genome affect clinical manifestation of symptomatic HCMV infection.MethodologyHCMV infection was detected by fluorescent PCR and immuno-histochemistry. The detection of genetic variants of four studied Micro-RNA tag-SNPs was done through PCR-RFLP assay and validated with DNA sequencing.ResultsWe observed an increased risk ranged from 3-folds to 5-folds among symptomatic HCMV cases for mutant genotype of rs2910164 (crude OR = 3.11, p = 0.009 and adjusted OR = 3.25, p = 0.007), rs11614913 (crude OR = 3.20, p = 0.006 and adjusted OR = 3.48, p = 0.004) and rs3746444 (crude OR = 4.91, p = 0.002 and adjusted OR = 5.28, p = 0.002) tag-SNPs. Interestingly, all the tag-SNPs that were significant after multiple comparisons at a FDR of 5% in symptomatic HCMV cases remained significant even after bootstrap analysis, providing internal validation to these results. Multifactor Dimensionality Reduction (MDR) analysis revealed 5-folds increased risk for symptomatic HCMV cases under the four-factor model (rs2910164, rs2292832, rs11614913 and rs3746444).ConclusionsThese results suggest that Micro-RNA gene variants of host-genome may affect clinical manifestation of symptomatic HCMV infection.     

PTPN22 polymorphisms,but not R620W,were associated with the genetic susceptibility of systemic lupus erythematosus and rheumatoid arthritis in a Chinese Han population

ObjectivesThe present study aimed to detect a possible association between PTPN22 gene polymorphisms and rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) in a Chinese Han population.Methods7 PTPN22 SNPs were genotyped in 358 patients with RA and 713 patients with SLE, as well as 564 RA controls and 672 SLE controls by Restriction Fragment Length Polymorphism (RFLP). Association analyses were conducted on the whole data set. Significant relationships were also examined between clinical features and SNPs for both RA and SLE.ResultsRs2476601 was lack of polymorphism with a ⩽0.1% frequency in both SLE and RA patients and healthy controls in our study. The two SNPs rs1217414 and rs3811021 of PTPN22 shown strong association with both SLE (rs1217414T: p_adj = 6.07e−004, OR = 0.57; rs3811021C: p_adj = 4.68e−005, OR = 0.65) and RA (rs1217414T: p_adj = 2.01e−008, OR = 0.26; rs3811021C: p_adj = 0.028, OR = 0.70). And the rs3765598 revealed a strong risk factor for SLE (p = 9.38e−009, p_adj = 6.57e−008, OR = 1.93), but not for RA (p = 0.48, OR = 1.12). Moreover, protective haplotype ACTTC in RA (p = 7.73e−016, p_adj = 5.51−015, OR[95%CI] = 0.02[0.002–0.10]) and SLE (p = 8.29e−018, p_adj = 5.80e−017, OR[95%CI] = 0.11[0.06–0.21]) were observed. In addition, the distribution of risk haplotypes ACGTC and GCTTT in RA (ACGTC: p = 0.0006, p_adj = 0.004, OR[95%CI] = 1.85[1.29–2.63]; GCTTT: p = 2.62e−005, p_adj = 1.85e−004, OR[95%CI] = 2.40[1.57–3.65]) and SLE (ACGTC: p = 0.0006, p_adj = 0.004, OR[95%CI] = 1.85[1.29–2.63]; ACGTC: p = 7.74e−011, p_adj = 6.81e−010, OR[95%CI] = 2.21[1.12–3.34]; GCTTT: p = 2.40[1.57–3.65], p_adj = 2.26e−006, OR[95%CI] = 2.64[1.79–3.87]) were significant different from that in controls. Furthermore, significant association was observed between the PTPN22 rs3765598 and antinuclear antibodies 1 (ANA1) in SLE.ConclusionsOur data provide strong evidence that the rs1217414 and rs3811021 in PTPN22 gene might be common protective factors contributed to SLE and RA susceptibility in the Chinese Han population. While, the rs3765598 might increase the genetic susceptibility of SLE, but not RA.     

Receptor for advanced glycation end products (RAGE) gene polymorphism and cardiovascular disease in end-stage renal disease patients

Background/objectivesReceptor for advanced glycation end products (RAGE) contributes to the pathogenesis of vascular and inflammatory diseases. We investigated whether the functional polymorphism in the promoter region of the RAGE gene (−374 T/A) influences development of cardiovascular disease in the end-stage renal disease (ESRD) patients.MethodsThe cohorts of 1866 ESRD patients and 1143 healthy subjects were genotyped by polymerase chain reaction (PCR) for the RAGE variant rs1800624.ResultsThe genotype and allele frequencies did not differ significantly between ESRD patients and controls. There was no significant difference in the genotype distribution when patients with CVD were compared to those without it (p for A allele = 0.62). After stratifying CVD patients according to CVD clinical phenotype, the ESRD patients with stroke had a lower frequency of A allele than patients without CVD (0.12 vs. 0.21, p = 0.027). To confirm this finding, we genotyped 163 patients with ischemic stroke but without renal disease. In this group, the AA/TA genotypes were also significantly associated with lower risk of stroke (OR 0.46, p = 0.0002).ConclusionOur data suggest that the presence of the A allele of −374 T/A polymorphism in the RAGE gene has a protective effect against stroke.     

A common variant near the PRL gene is associated with increased adiposity in males

A common variant (rs4712652) adjacent to the prolactin gene was recently associated with obesity using a genome-wide association study. The aim of this study was to replicate the association between rs4712652 and obesity and further examine if rs4712652 is associated with fat percentage and adiponectin levels in a population based Scandinavian cohort. rs4712652 was genotyped in 4879 participants (mean BMI 26.5 ± 4.5 kg/m²) from the population-based PPP-Botnia Study and related to BMI, fat percentage and adiponectin levels. We found that the risk A allele of rs4712652 is associated with increased BMI and fat percentage in males (P = 0.0047 and P = 0.025, respectively), but not in females (P = 0.98, P = 0.45). Male A allele carriers have a higher risk of being overweight with an OR of 1.16 (P = 0.025). While there was a significant negative correlation between adiponectin levels and fat percentage (r = ?0.36; P = 0.039) in male carriers of the protective GG genotype, this correlation was lost in male carriers of the risk rs4712652 A allele (P = 0.33). Thus, the common SNP rs4712652 near the PRL gene seems to affect body fat and adiposity in a sex-specific fashion. It remains to be shown whether this is mediated by different prolactin concentrations or differences in tissue sensitivity to prolactin.     

Comprehensive review of genetic association studies and meta-analysis on miRNA polymorphisms and rheumatoid arthritis and systemic lupus erythematosus susceptibility

BackgroundMicroRNAs (miRNAs), small RNA molecules, play a role in the development and differentiation of immune cells in both innate and adaptive immune responses. Our study was aimed to investigate the association between three miRNA polymorphism and rheumatoid arthritis (RA) or systemic lupus erythematosus (SLE) by using meta-analysis approach.MethodsA PubMed database search was conducted during August 2013 to identify case–control studies of miRNAs and RA or SLE risk. Two authors independently extracted information on the study design, the characteristics of the study participants, exposure and outcome assessments. The fix-effects and random-effects models were used for the risk estimates by Stata 11.0 software.ResultsOur meta-analysis of six case–control studies involving a total of 998 RA cases and 1493 controls identified no significant association between mir-146a rs2910164 and RA, with an overall OR of 0.843 (95% CI = 0.642–1.105; CC vs. GG). No association was observed in three studies with a total of 1532 cases and 2168 controls between miR-146a rs2910164 and SLE risk (OR = 0.911, 95% CI = 0.710–1.171; CC vs. GG). Three studies with a total of 529 cases and 595 controls evaluated the mir-499 rs3746444 polymorphism and its association with RA. There was a decreased overall risk of RA under the allelic and genotypic models [OR = 0.616, 95% CI = 0.384–0.981, (T vs. C allele) and OR = 0.386, 95% CI = 0.226–0.659, (TT vs. CC)]. Two studies with 4826 cases and 4181 controls evaluated miR-146a rs57095329 and its association with SLE. There was a significant association between miR-146a rs57095329 and SLE (OR = 1.263, 95% CI = 1.136–1.405, G vs. A allele).ConclusionsThe present meta-analysis suggests important roles for the mir-499 rs3746444 polymorphism in RA, especially in the Caucasian population and for miR-146a rs57095329 polymorphism in SLE. Further studies with large sample size are needed to confirm these associations.     

Association between polymorphisms in erythropoietin gene and upper limit haematocrit levels among regular blood donors

Purpose of the studyErythropoietin (EPO) is a glycoprotein hormone that functions primarily on the stimulation and control of erythropoiesis in bone marrow. In this study, polymorphisms in EPO gene; C3434 T, G3544 T (rs551238) and rs1617640 were evaluated to determine their frequencies and genotype distribution patterns among blood donors with upper-limit haematocrit level.Subjects and methodsA total of 298 subjects, 181 blood donors with haematocrit level greater or equal to 48% and 117 donors with haematocrit between 42–47.5% as control were recruited. All subjects were genotyped for C3434 T, rs551238 polymorphisms and for rs1617640 using restriction fragment length polymorphism method (PCR-RFLP) and sequencing techniques.ResultsA significant difference was found in rs1617640 and rs551238 genotype frequencies in blood donors with upper-haematocrit compared to the control group (P < 0.05). In accordance with genotype frequencies, G allele in these two polymorphisms were found at higher frequency among upper-haematocrit group compared to the control (P < 0.05). On the other hand, C3434 T polymorphism was not significantly different between the two groups, neither for genotype frequencies nor for allele frequencies.ConclusionResults suggest a strong association between rs551238 and rs1617640 polymorphisms in the EPO gene and upper-limit haematocrit level among blood donors.     

A meta-analysis of the relationship between MYO9B gene polymorphisms and susceptibility to Crohn’s disease and ulcerative colitis

ObjectiveBoth Crohn’s disease (CD) and ulcerative colitis (UC) have a complex etiology involving multiple genetic and environmental factors. Multiple UC and CD susceptibility genes have been identified through genome-wide association studies and subsequent meta-analyses. The aim of this meta-analysis was to clarify the impact of MYO9B gene polymorphisms on CD and UC risk.MethodsThe PubMed, Elsevier Science Direct and Embase databases were searched to identify eligible studies that were published before October 2014. Data were extracted and pooled crude odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated.ResultsA total of 11 studies, containing 3297 CD cases, 3903 UC cases and 8174 controls were included in this meta-analysis. Bonferroni correction results showed that rs1545620 A/C polymorphism of MYO9B gene was associated with both CD and UC susceptibility in Caucasians (OR = 0.88, 95% CI = 0.82 ∼ 0.95, P = 0.001; OR = 0.82, 95% CI = 0.76 ∼ 0.89, P < 0.001), but not in Chinese. rs1457092 G/T and rs2305764 C/T polymorphisms are associated with UC susceptibility (OR = 0.85, 95% CI = 0.79 ∼ 0.91, P < 0.001; OR = 0.88, 95% CI = 0.83 ∼ 0.93, P < 0.001), but not with CD susceptibility in Caucasians.ConclusionsThis meta-analysis suggested that rs1545620 is both CD and UC susceptible locus in Caucasians; rs1457092 and rs2305764 are UC susceptible loci, but are not CD susceptible loci in Caucasians. Further studies with more sample size are needed for a definitive conclusion.