Preliminary evidence of association between EFHC2, a gene implicated in fear recognition,and harm avoidance

Genetic variation at the EF-hand domain containing 2 gene (EFHC2) locus has been associated with fear recognition in Turner syndrome. The aim of this study was to examine whether EFHC2 variants are associated with non-syndromic anxiety-related traits [harm avoidance (HA) and behavioral inhibition (BI)] and with panic disorder (PD). Our sample comprised 127 PD patients and 132 controls without psychiatric disorder. We genotyped nine SNPs within the EFHC2 locus and used PLINK to perform association analyses. An intronic SNP (rs1562875) was associated with HA (permuted p = 0.031) accounting alone for over 3% of variance in this trait. This same SNP was nominally, but not empirically, associated with BI (r² = 0.022; nominal p = 0.022) and PD (OR = 2.64; nominal p = 0.009). The same association was found in a subsample of only females. In sum, we observed evidence of association between a variant in EFHC2, a gene previously associated with the processing of fear and social threat, and HA. Larger studies are warranted to confirm this association.     

Microtubule-associated protein tau (MAPT) influences the risk of Parkinson's disease among Indians

Parkinson's disease (PD) is a neurodegenerative disease of the central nervous system and its prevalence increases with age. Microtubule-associated protein tau (MAPT), a neuronal protein is involved in the pathogenesis of several neurodegenerative diseases including PD. To determine the broader significance of this association with PD, replicative studies in distinct ethnic populations are required. In this study, we investigated MAPT for its potential association with PD using five haplotype-tagging SNPs and the del-In9 polymorphism of MAPT in 301 PD patients and 243 healthy controls from eastern India. Our case–control analysis did not show a significant association with any of the markers and PD. However, a risk haplotype [GAC + G] for PD was identified (OR = 1.563; 95% CI = 1.045–2.337; p = 0.03). In addition, haplotype AAC + A (OR = 2.787; 95% CI = 1.372–5.655; p = 0.004) was strongly associated with early onset PD (age at onset ≤40 years) and AAC + G haplotype showed a weak association (OR = 2.233; 95% CI = 1.018–4.895; p = 0.045) with late onset PD (age at onset >40 years). This observation highlights the significance of rs7521 in modifying the age at onset of PD under a common haplotype background. We also identified AGC + A as a risk haplotype for sporadic cases (OR = 2.773, 95% CI = 1.198–6.407, p = 0.016). This is the first association study from India conducted on MAPT among PD patients and provides valuable information for comparison with other ethnic groups.     

Fibulin-5 (FBLN5) gene polymorphism is associated with pelvic organ prolapse

Objective

FBLN5 encodes a key protein of elastic fiber matrix assembly and function that contributes to maintaining pelvic support and plays the important role in the pathophysiology of pelvic organ prolapse (POP). The aim of the study was to investigate whether there is an association between common single-nucleotide polymorphisms (SNPs) of the FBLN5 gene and POP.

Study design

A total of eleven tag SNPs of the FBLN5 gene were genotyped using the polymerase chain reaction with confronting two-pair primers (PCR-CTPP) in 210 patients with POP (stages III–IV) and 292 controls with no even minimal POP.

Results

We revealed significant associations of tag SNPs rs2018736 and rs12589592 with POP. The top association signal was found for SNP rs2018736 (protective effect for the minor allele A) in the entire set: p = 0.0026, OR = 0.42, 95% CI: 0.24–0.75; in the stratum with pelvic floor trauma: p = 0.0018, OR = 0.27, 95% CI: 0.11–0.64; and in the stratum with fetal macrosomia: p = 0.013, OR = 0.14, 95% CI: 0.03–0.71. The results of the haplotype analyses were consistent with the single SNP analysis. In the strata without perineal trauma and fetal macrosomia effects were non-significant, possibly, due to the smaller effect sizes.

Conclusions

Current data provide, for the first time, strong evidence that common SNPs of the FBLN5 gene are associated with POP especially after pelvic floor injury.     

The potential role of VPREB1 gene copy number variation in susceptibility to rheumatoid arthritis

Although the etiology of rheumatoid arthritis (RA) remains unknown, it has been widely suggested that RA has a genetic background. In humans, a copy number loss of 22q11.2, a region harboring the VPREB1 gene, has been suggested to be associated with several immunologic disorders, but there has been no study on the copy number variation (CNV) of the VPREB1 and its potential association with RA. Here, we explored the association between the RA and the CNV of the VPREB1 gene by performing genomic quantitative PCR and quantification of B cell subsets in RA patients and controls. The proportion of the individuals with <2 copies of the VPREB1 gene was significantly higher in the patient group than that in the controls (12.9% vs 0.9%, p < 0.0001), while that of the individuals with >2 copies was lower in the patient group than that in the controls (1.7% vs 18.9%, p < 0.0001). The odds ratio (OR) of the individuals with <2 copies was significantly higher compared with the odds ratio of those individuals with 2 copies (OR = 12.1, 95% confidence interval (CI) 2.8-51.6). Likewise, the OR of the individuals with >2 copies was significantly lower than the OR of those individuals with 2 copies (OR = 0.09, 95% CI 0.03-0.3). We also found that the proportion of CD21⁻CD23⁻ B cells was significantly higher in the RA patients compared with that of the controls (11.9% vs 5.7%, p = 0.002), but the proportion of CD21⁺CD23⁺ cells was significantly lower in the RA patients (26.2% in RA vs 34.9% in the controls, p = 0.005). To the best of our knowledge, this is the first evidence showing the association between a low copy number of the VPREB1 gene and RA, and this may help understanding the pathogenesis of RA and other autoimmune disorders.     

SNP/haplotype associations of CCR2 and CCR5 genes with severity of chagasic cardiomyopathy

Background

Chronic inflammation plays a major role in the tissue injury seen in the chronic chagasic cardiomyopathy. The CCR2 and CCR5 chemokine receptors are involved with the type of cellular infiltrate present in cardiac tissue and CCR5-gene variants were previously associated with this pathology.

Methods and results

This is a replication study in an independent cohort with larger sample size. Nine SNPs of CCR5 and CCR2 were typified to confirm the association previously found with Chagas disease. Evidence of association with severity was found for the A allele of rs1799864 of CCR2 (p_ad = 0.02; OR = 1.91, 95% CI = 1.10–3.30), the T allele of the rs1800024 of CCR5 (p_ad = 0.01; OR = 1.95, 95% CI = 1.13–3.38), and the HHF^∗2 haplotype (p = 0.03, OR = 1.65, 95% CI = 1.03–2.65). These results were replicated in the study combined with previous data. In this analysis it was replicated the allele T of rs2734648 (p_ad = 0.009, OR = 0.52, 95% CI = 0.32–0.85) with protection. In addition, the allele G of rs1800023 (p_ad = 0.043, OR = 0.61, 95% CI = 0.38–0.98), and the HHC haplotype (p = 0.004, OR = 0.62, 95% CI = 0.44–0.86) were also associated with protection. In contrast, the allele A of rs1799864 of CCR2 (p_ad = 0.009; OR = 1.90, 95% CI = 1.17–3.08); and the allele T of rs1800024 of CCR5 (p_ad = 0.005, OR = 1.98, 95% CI = 1.22–3.23) were associated with greater severity. No evidence of association between symptomatic and asymptomatic patients was observed.

Conclusions

These results confirm that variants of CCR5 and CCR2 genes and their haplotypes are associated with the severity but not with susceptibility to develop chagasic cardiomyopathy.     

Associations of killer cell immunoglobulin like receptors with rheumatoid arthritis among North Indian population

Introduction

Rheumatoid arthritis (RA) is an autoimmune and chronic inflammatory disease of unknown etiology. Killer cell immunoglobulin-like receptors (KIR) expressed on surface of natural killer cells and CD28 null T-cells which are present in synovial membrane of RA. The present study has evaluated associations of KIR genes with RA among North Indian population from Uttar Pradesh.

Materials and methods

KIR genotypes were determined in 100 RA cases and 100 healthy controls using sequence specific primer polymerase chain reaction (PCR-SSP) method.

Results

RA cases positive for KIR3DS1 (OR = 1.17, p-value = 0.0498) and KIR2DS2 (OR = 2.21, p-value = 0.0120) showed risk associations. While, KIR2DL2 (OR = 0.40, p-value = 0.0026), KIR2DL3 (OR = 0.44, p-value = 0.0283) and KIR3DL1 (OR = 0.32, p-value = 0.0012) showed protective associations. Increased incidence of BB genotype (45%) was revealed among cases. Risk association was noted against telomeric region (OR = 2.12, p = 0.0120) genes for RA. Pair-wise linkage disequilibrium (LD) analysis among RA cases revealed KIR2DS1-2DL1 (D′ = 0.83, r² = 0.36), KIR3DL1-3DS1 (D′ = 1, r² = 0.58) and KIR2DL1-2DL2 (D′ = 1, r² = 0.61) to be in significant LD. KIR3DS1 and KIR2DS3 genes showed significant risk associations among RA patients with extra-articular manifestations (OR = 5.14, p-value = 0.0018; OR = 3.79, p-value = 0.0106) and in limited range of motion in affected joints (OR = 14.91, p-value = 0.0001; OR = 2.95, p-value = 0.0126).

Conclusion

The KIR activating genes have risk association with RA in the present study.     

Association of the suppressor of cytokine signaling 1 (SOCS1) gene polymorphisms with acute coronary syndrome in Mexican patients

Recent studies provide evidence on the emerging role of the SOCS1 gene in the development and progression of atherosclerotic lesions. This gene encodes for the suppressor of the cytokine signaling-1 protein that interacts directly with the Janus kinases that are essential intracellular mediators of the immune cytokine action. The aim of this study was to test for associations between SOCS1 gene single nucleotide polymorphisms (SNPs) and the risk of developing acute coronary syndromes (ACS) in a group of Mexicans patients. Four SNPs [-3969 C > T (rs243327), -1656 G > A (rs243330), -820 G > T (rs33977706) and +1125 G > C (rs33932899)] of SOCS1 gene were determined for TaqMan genotyping assays in a group of 447 patients with ACS and 622 healthy controls. Under heterozygous model, the -3969 C > T (rs243327) SNP was associated with increased risk of ACS (OR = 1.45, P_Het = 0.021). On the other hand, under co-dominant and heterozygous models, the -1656 G/A (rs243330) SNP was associated with increased risk of ACS (OR = 1.47, P_Co-dom = 0.038 and OR = 1.50, P_Het = 0.013, respectively). Moreover, under co-dominant, dominant, and heterozygous models, the -820 T/G (rs33977706) SNP was associated with increased risk of ACS (OR = 1.59, P_Co-dom = 0.03, OR = 1.48, P_Dom = 0.028 and OR = 1.61, P_Het = 0.01). Finally, under co-dominant and heterozygous models, the +1125 G/C (rs33932899) SNP was associated with increased risk of ACS (OR = 1.54, P_Co-dom = 0.006, OR = 1.58, P_Het = 0.012, respectively). Models were adjusted for gender, age, body index mass, dyslipidemia, alcohol consumption, and smoking. In summary, our data suggests that the four studied polymorphisms of the SOCS1 gene play an important role as susceptibility markers for developing ACS.     

Associations between interleukin-10 polymorphisms and susceptibility to systemic lupus erythematosus: A meta-analysis

Objective

The study determined whether interleukin-10 (IL-10) polymorphisms confer susceptibility to systemic lupus erythematosus (SLE).

Methods

A meta-analysis was conducted on the associations between the IL-10-1082 G/A, -819 C/T, -592 C/A polymorphisms and the haplotype of the IL-10-1082 G/A, -819 C/T, -592 C/A polymorphisms and SLE.

Results

A total of 19 studies involving 2828 SLE patients and 4008 controls were considered in the meta-analysis. Meta-analysis of the IL-10-1082 G/A polymorphism revealed an association between SLE and the IL-10-1082 G allele (odds ratio [OR] = 1.158, 95% confidence interval [CI] = 1.051–1.276, p = 0.003). Stratification by ethnicity indicated an association between the IL-10-1082 G allele and SLE in Europeans (OR = 1.160, 95% CI = 1.039–1.296, p = 0.008). Meta-analysis stratified by ethnicity produced an association between the IL-10-819 C allele and SLE in Asians (OR = 1.308, 95% CI = 1.030–1.619, p = 0.027). Meta-analysis of the homozygous GCC/GCC haplotype failed to show a significant association with SLE in Europeans (OR = 1.223, 95% CI = 0.981–1.526, p = 0.074). However, meta-analysis of the GCC haplotype revealed a significant association with RA in all study subjects (OR = 1.402, 95% CI = 1.001–1.964, p = 0.049). Stratification by ethnicity indicated an association between the GCC haplotype and SLE in Europeans (OR = 1.656, 95% CI = 1.087–2.523, p = 0.019), but not in Asians (OR = 1.100, 95% CI = 0.703–1.721, p = 0.677). Meta-analysis of homozygous ATA/ATA haplotype failed to show a significant association with SLE in overall and European groups. However, meta-analysis of the ATA haplotype revealed a significant association with SLE in all study subjects (OR = 1.516, 95% CI = 1.039–2.213, p = 0.031) and Asians (OR = 2.580, 95% CI = 2.086–3.192, p < 1 × 10⁻⁹), but not in Europeans (OR = 1.233, 95% CI = 0.816–1.862, p = 0.320).

Conclusions

This meta-analysis suggests that the IL-10 polymorphisms confer susceptibility to SLE in Europeans and in Asians.     

Association study between two novel single nucleotide polymorphisms and sporadic Parkinson's disease in Chinese Han population

Two novel single nucleotide polymorphisms (SNPs) (rs6812193 and rs11868035) were recently identified to be associated with Parkinson's disease (PD) in a Web Based Genome-Wide Association Study. Herein, we conducted a case–control study to evaluate the possible associations between these two SNPs and PD in Chinese Han population. All subjects (501 sporadic PD patients and 502 normal controls) were genotyped using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis with these two SNPs. Chi-square test revealed no significant difference in either genotype frequencies or allele frequencies, even after being stratified by age. But we found that the genotype and allele frequency of rs6812193 shows difference between male patients and male controls (p = 0.031, OR = 0.584; p = 0.037, OR = 0.606) but none in the female. Our findings suggest that rs11868035 may have no association with PD in Chinese population and rs6812193 may have marginal association with PD in male Chinese population. However, due to the limited data in the present study, replication studies in larger sample and other populations are required.     

Association of ADIPOQ polymorphisms with obesity risk: A meta-analysis

Background

The association between ADIPOQ polymorphisms and the risk of obesity remains controversial. We perform a comprehensive meta-analysis to clarify the current understanding of this association.

Methods

We searched for relevant studies in PubMed, Embase and Cochrane library before February 2014. The strengths of the association between ADIPOQ polymorphisms and obesity risk were estimated by odds ratios (OR) with 95% confidence intervals (CI).

Results

Eighteen case–control studies analyzing four SNPs (rs17300539, rs266729, rs1501299 and rs2241766) of ADIPOQ gene were eligible for the present meta-analysis. The pooling results showed that rs17300539 (2GG+GA vs. 2AA+GA: OR = 0.78, 95%CI = 0.69–0.89) and rs1501299 (2GG+GA vs. 2AA+GA: OR = 0.89, 95%CI = 0.80–0.98) were associated with obesity risk in Caucasian ethnicity. The rs266729 were associated with obesity risk in Asian ethnicity (2CC+CG vs. 2GG+GCG: OR = 0.77, 95%CI = 0.65–0.92). However, there were no associations between rs2241766 and the obesity risk (P > 0.05). No publication bias was found among these studies (all P > 0.05).

Conclusions

This study suggests that ADIPOQ rs17300539 and rs1501299 are associated with risk of obesity in Caucasian ethnicity, and the rs266729 is associated with obesity risk in Asian ethnicity. However, there is no association between rs2241766 and obesity risk.     

Supportive evidence for neuregulin 1 as a susceptibility gene for schizophrenia in a Japanese population

Schizophrenia is a complex genetic disorder and affects approximately 1% of the population worldwide. Recently, Stefansson et al. identified neuregulin 1 (NRG1) on 8p12 as a susceptibility gene for schizophrenia in the Icelandic population. It was reported that the at-risk haplotype (“Hapice”) constructed from five SNPs and two microsatellite markers was found to be over-represented in patients with schizophrenia compared to controls. Since then several independent studies have supported the association of NRG1 with schizophrenia. We performed a case–control association study using the four SNPs in a Japanese sample. We genotyped three SNPs (SNP8NRG221533, SNP8NRG241930, and SNP8NRG243177) from Stefansson et al. and one SNP (rs1081062) located in intron 1 of NRG1. There were no significant differences in allele frequencies for each SNP between cases and controls, however, homozygotes of minor alleles in SNP8NRG241930, SNP8NRG243177, and rs1081062 were associated with an increased risk of schizophrenia (P = 0.025, OR = 4.14; P = 0.041, OR = 1.43; and P = 0.0023, OR = 3.06, respectively). Furthermore, the haplotype constructed from four SNPs shows a significant association with schizophrenia (permutation P = 0.026). Our data support the hypothesis that NRG1 gene is a susceptibility gene for schizophrenia.     

Vascular endothelial growth factor (VEGF) polymorphism is associated with treatment resistant depression

Antidepressive medication and electroconvulsive therapy (ECT) increase hippocampal neurogenesis by promoting expression of trophic factors, including brain-derived neurotrophic factor (BDNF) and vascular endothelial growth factor (VEGF). The aims were to test for an association between the VEGF 2578 C/A polymorphism and major depressive disorder (MDD) in two patient populations compared to controls, and the association between this polymorphism and response to serotonin selective reuptake inhibitors (SSRI) and to ECT. The first patient sample consisted of 119 subjects with treatment resistant major depressive disorder who were treated with ECT and the second of 98 depressive patients treated with SSRI. Treatment response was assessed by the Montgomery and Åsberg Depression Rating Scale (MADRS). Patients scoring <8 in post-treatment MADRS were considered remitters. There was a trend that CC genotype of VEGF 2578 C/A polymorphism was more common in ECT-treated and SSRI-treated patients than in controls (31.1%, 25.5% and 18.7% respectively; p = 0.056). The VEGF 2578 C/A polymorphism was associated with treatment resistant MDD. CC genotype was more common in ECT patients than in controls (31.1% and 18.7% respectively; p = 0.015). The VEGF 2578 C/A polymorphism was not associated with treatment response to SSRI or to ECT. The finding suggests an association between VEGF 2578 C/A polymorphism and treatment resistant depression which is reported for the first time. Further studies with larger samples will be required to confirm the results.     

IL10 polymorphisms associated with Behçet’s disease in Chinese Han

Objective

IL-10 is a potent anti-inflammatory cytokine that plays important roles in the pathogenesis of Behçet’s disease (BD). Two genome-wide association studies have identified IL10 as a potential risk factor for BD. Here, we investigated the association between IL10 polymorphisms and BD in Chinese Han.

Methods

407 BD patients and 679 healthy controls were enrolled, and genotyped by Sequenom MassArray system (Sequenom iPLEX assay, San Diego, CA).

Results

The frequency of risk allele of rs1800871 was notably higher in BD patients than in controls (71.9% vs. 66.2%, OR: 1.30, 95%CI: 1.08–1.58, p_c = 0.024). Similarly, rs1518111, which showed strong linkage disequilibrium (r² = 1) with allele rs1800871, was also associated with BD (p_c = 0.026). Rs3021094 was in association with BD in a dominant model (p_c = 0.035), and the haplotype (GACC) formed by rs1518111, rs3021094, rs3790622, and rs1800871 was associated with BD (p_c = 0.023). Results obtained from meta-analysis combined with our data showed that rs1800871 and rs1518111 were associated with BD.

Conclusion

IL10 may be the susceptibility gene for BD in Chinese Han population.     

Anterior genu corpus callosum and impulsivity in suicidal patients with bipolar disorder

Suicidality is a life-threatening symptom in patients with bipolar disorder (BD). Impulsivity and mood instability are associated with suicidality in mood disorders. Evidence suggests that gray and white matter abnormalities are linked with impulsivity in mood disorders, but little is known about the association between corpus callosum (CC) and impulsivity in BD. We examined the relationship between CC areas, impulsivity and suicidality in BD patients. We studied 10 female BD patients with a history of suicide attempt (mean ± SD age 36.2 ± 10.1 years), 10 female BD patients without suicide attempt history (44.2 ± 12.5 years) and 27 female healthy subjects (36.9 ± 13.8 years). Impulsivity was evaluated by the Barratt Impulsivity Scale (BIS). We traced MR images to measure the areas of the CC genu, anterior body, posterior body, isthmus and splenium. The genu was divided into anterior, middle and posterior regions. The suicidal and non-suicidal BD patients had significantly higher BIS total, attention and non-planning scores than the healthy subjects (ps < 0.01), and the suicidal BD patients had significantly higher BIS motor scores than the non-suicidal BD and healthy subjects (ps < 0.01). There were no significant differences among the three groups on any regional CC areas, although the suicidal BD patients had the smallest areas. The suicidal BD patients showed a significant inverse correlation between anterior genu area and the BIS total (r = −0.75, p = 0.04), motor (r = −0.79, p = 0.02) and non-planning scores (r = −0.79, p = 0.02). These correlations were not found in the non-suicidal BD patients or healthy subjects. The results suggest that the anterior medial frontal region may be involved in the pathophysiology of impulsive and suicidal behaviors in BD.     

Significance of association of HLA-C and HLA-E with psoriatic arthritis

Psoriatic arthritis (PsA) is a complex genetic disorder that results from an interplay between multiple genetic and environmental factors. The aim of the study was to assess the significance of the association between the HLA-C and HLA-E allelic groups and PsA. Our results confirm the association between HLA-C^∗06 and PsA (OR = 5.16, p < 0.0001). Furthermore, HLA-C^∗06-positive patients develop more severe disease (p < 0.01) and more frequently present with polyarticular pattern of PsA (p = 0.08). Additionally our study revealed that the HLA-C^∗02 allele was more frequently observed in PsA patients (OR = 5.40, p < 0.0005) and also that the HLA-E^∗01:01 allele was significantly over-represented among HLA-C^∗02-negative patients in comparison to healthy individuals (OR = 6.44, p = 0.045). Therefore these results suggest that the HLA-E and HLA-C^∗02 molecules may also play an important role in determination immune response contributing to the PsA development.     

Association analysis of GRIN1 and GRIN2B polymorphisms and Parkinson's disease in a hospital-based case–control study

Hyperactivation of N-methyl-d-aspartate receptors (NMDARs) leads to neuronal excitotoxicity and is suggested to play a role in many brain disorders, including Alzheimer's disease and schizophrenia. However, the association between polymorphisms in the genes that code for NMDAR subunits, N-methyl-d-aspartate 1 and 2B (GRIN1 and GRIN2B) and Parkinson's disease (PD) remains unclear. In a hospital-based case–control study of PD, DNA samples were collected from 101 PD patients and 205 healthy controls. Genotyping assays were used to screen for polymorphisms in the GRIN1 (rs2301364 T > C, rs28489906 T > C, and rs4880213 T > C) and GRIN2B (C366G, C2664T, and rs1805476 T > G) genes, and logistic regression analysis was then used to assess the association between these single nucleotide polymorphisms (SNPs) and PD susceptibility. None of the 6 SNPs were significantly associated with PD risk on their own. However, in conjunction with putative low-risk genotypes for the GRIN1 gene, the GRIN2BC366G variant was significantly associated with reduced PD risk compared with the homozygous genotype 366CC (OR = 0.38, 95%CI = 0.17–0.93, P = 0.033). A synergistic effect on risk reduction was observed in subjects who carried multiple polymorphisms of GRIN1 and the GRIN2BC366G polymorphism (OR = 0.78, 95%CI = 0.59–1.02, P_trend = 0.073). Our results suggest that polymorphisms in the GRIN1 and GRIN2B genes may serve as potential biomarkers for a reduced risk of PD among the Chinese population in Taiwan.     

Vascular endothelial growth factor gene polymorphisms and vasculitis susceptibility: A meta-analysis

Objective

The aim of this study was to explore whether vascular endothelial growth factor (VEGF) polymorphisms are associated with susceptibility to vasculitis.

Methods

Meta-analyses were conducted on the associations between the −634 C/G, +936 C/T, −1154 A/G, and −2578 A/C polymorphisms of VEGF and vasculitis.

Results

Eight studies on VEGF polymorphisms and vasculitis involving 2740 subjects (vasculitis 834, controls 1906) were included in this meta-analysis. The meta-analysis showed no association between vasculitis and the VEGF −634 C allele (OR = 1.161, 95% CI = 0.921–1.464, p = 0.207) among study subjects. Meta-analysis showed no association between vasculitis and the VEGF + 936 T allele (OR = 1.121, 95% CI = 0.905–1.390, p = 0.295). However, stratification by ethnicity indicated a significant association between the VEGF + 936 T allele and vasculitis in Europeans, but not in Asians (OR = 1.486, 95% CI = 1.038–2.128, p = 0.030; OR = 0.958, 95% CI = 0.773–1.253, p = 0.755). Meta-analysis showed no association between vasculitis and the VEGF −1154 A/G and 2578 A/C polymorphisms.

Conclusions

This meta-analysis suggests that the VEGF + 936 T allele is associated with susceptibility to vasculitis in Europeans, but not in Asians.     

Association between functional Fc receptor-like 3 (FCRL3) −169 C/T polymorphism and susceptibility to seropositive rheumatoid arthritis in Asians: A meta-analysis

Objective

The aim of this study was to determine whether the functional Fc receptor like-3 (FCRL3) −169 C/T polymorphism confers susceptibility to rheumatoid arthritis (RA).

Methods

A meta-analysis was conducted on the associations between the FCRL3 −169 C/T polymorphism and RA.

Results

A total of 17 comparison studies including 11,170 patients and 11,142 controls were considered in the meta-analysis. The meta-analysis showed no association between RA and the FCRL3 −169 C allele in study subjects (OR = 1.046, 95% CI = 0.997–1.098, p = 0.068). Stratification by ethnicity indicated an association between the FCRL3 −169 C allele and RA in Asians (OR = 1.101, 95% CI = 1.035–1.174, p = 0.002), but not in Europeans. Stratification of patients according to the presence of rheumatoid factor (RF) revealed a different significant association between the C allele and RA in RF-positive and RF-negative RA patients. Stratification by ethnicity indicated an association between the FCRL3 −169 C allele and RF-positive RA in Asians (OR = 1.093, 95% CI = 1.004–1.189, p = 0.040), but not in Europeans.

Conclusions

This meta-analysis demonstrates that the FCRL3 −169 C/T polymorphism may confer susceptibility to seropositive RA in Asians.     

Association of genetic variation in CACNA1C with bipolar disorder in Han Chinese

Background

A growing body of evidence highlights the existence of shared genetic susceptibility to both major depressive disorder (MDD) and bipolar disorder (BD), suggesting some potential genetic overlap between the disorders. Genome-wide association studies have identified consistent association of single nucleotide polymorphisms of the α-1 C subunit of the L-type voltage-gated calcium channel gene (CACNA1C) with MDD and BD, suggesting CACNA1C as a promising candidate gene for susceptibility to mood disorders. In the present study, we tested the association of CACNA1C with MDD and BD in Han Chinese.

Methods

We genotyped three potentially functional polymorphisms in 635 MDD patients, 286 BD patients and 730 normal, control patients.

Results

The genotype frequencies of SNP rs1051375 showed statistically significant differences between the BD and control groups (P=0.005). At the allele level, the difference of G allele frequency of rs1051375 between BD patients and control subjects was also significant (P=0.011; OR=1.30, 95% CI: 1.06–1.58). We found that GG genotype of rs1051375 carriers had a lower age at onset than those with the AG or AA genotype, and the mean±standard deviation ages at onset of GG, AG and AA carriers were 24.04±4.22, 25.76±4.75 and 25.78±4.33 years, respectively. Neither genotype nor allele frequencies of the three polymorphisms were found to be significantly different between the MDD patients and control subjects.

Limitations

The relative small sample size in BD group should be considered a limitation of this study.

Conclusions

Our initial findings support a potential association of CACNA1C as a genetic risk factor for BD susceptibility.     

Distribution of Killer cell immunoglobulin like receptor genes in end stage renal disease among North Indian population

Introduction

NK cell function is regulated by cell surface inhibitory and activating receptors including the C-type lectin receptors and Killer Immunoglobulin-like receptors (KIR). The effect of immune modulating cytokines produced by NK cells in the pathogenesis of end stage renal disease (ESRD) remained intriguing. In this regard the present study assesses the combinatorial association of KIR gene content and KIR receptor–HLA ligand in the North Indian ESRD patients.

Material and methods

KIR gene polymorphism as a susceptible marker in ESRD among 512 patients and 512 ethnically matched controls was analyzed. PCR-SSP based genotyping for KIR gene content and HLA-A, B, C typing was carried out.

Results

Significant difference in frequencies of KIR2DS1–HLA-C2 (p ? 0.0001, OR = 1.98, CI = 1.50–2.61), KIR2DS2–HLAC1 (p ? 0.0001, OR = 1.87, CI = 1.42–2.46), KIR3DS1–HLA-Bw4 (p = 0.0038, OR = 1.46, CI = 1.13–1.88) combinations for ESRD was found. In the combinatorial analysis Bw4⁺/3DL1⁻/3DS1⁺ (p ? 0.0001, OR = 4.90, CI = 2.75–8.71) and C1⁺/2DL2⁻/2DL3⁻/2DS2⁺/2DS3⁺ (p = 0.0037, OR = 2.50, CI = 1.35–4.63) showed risk association. KIR3DS1 was observed to be susceptible for all four primary kidney disease groups.

Conclusion

NK cell de-regulation due to HLA ligand binding KIR receptors may be involved in the patho-physiology of ESRD. Upon analyzing the data in this context it was found that C2/C2 donor might improve the clinical outcome of patients having C2 ligands.