Effect of 5-haplotype of dysbindin gene (DTNBP1) polymorphisms for the susceptibility to bipolar I disorder.

We investigated a possible association between dysbindin gene (DTNBP1) variants and bipolar I disorder (BID). Five SNPs within DTNBP1 (rs3213207, rs1011313, rs2005976, rs760761, and rs2619522) were genotyped for 151 patients with BID and 478 controls. We observed a significant protective association of the haplotype A-C-G-T-A (all SNPs, P = 0.00016) and particularly G-T-A (the last three SNP, P = 0.00007) within DTNBP1 variants investigated. Single marker and subgroup (e.g., psychotic features, age at onset, family history, etc.) analyses showed no significant association. Although the association was due to a small number of subjects, specific DTNBP1 haplotypes, previously associated with schizophrenia, may be also associated with BID. Adequately powered studies from different ethnicities will be necessary to confirm our findings.     

Association of intron 1 variants of the dopamine transporter gene with schizophrenia

The dopamine transporter (DAT1) gene has been implicated in the pathogenesis of many neuropsychiatric disorders, including schizophrenia. The present study aimed to investigate association of the DAT1 gene polymorphisms with schizophrenia in a Han Chinese population. Two single nucleotide polymorphisms (SNPs) in the DAT1 gene (rs2975223 and rs2455391) were tested in 368 patients with schizophrenia and 420 healthy controls, of whom 293 patients underwent an assessment of psychotic symptoms through the positive and negative syndrome scale (PANSS). The chi-square test (χ²) showed disease association for rs2455391 (corrected p = 0.023 for allelic association and p = 0.034 for genotypic association, respectively). The rs2975223(G)–rs2455391(C) haplotype was associated with increased risk of the illness (p = 0.0012, OR = 2.09, 95% CI = 1.28–3.42). Quantitative trait analysis showed that rs2455391 was associated with positive symptoms, general symptoms and global symptoms but not with negative symptoms. The present results suggest that the DAT1 gene may be mainly involved in the development of the positive symptoms in the Chinese population.     

DNA methyltransferase 3B gene increases risk of early onset schizophrenia

Objective: Consistent evidence indicated that aberrant DNA methylation may be involved in the development of schizophrenia. DNA methyltransferase 3B (DNMT3B) is the key methyltransferase in DNA methylation regulations. In this study, we investigated the association between DNMT3B polymorphisms and the susceptibility of early onset schizophrenia in Chinese Han population. Methods: Case–control (patients = 381 and controls = 472) and family based (trios = 103) study was performed through genotyping two tag single nucleotide polymorphisms (rs2424908 and rs6119954) covering the whole DNMT3B gene. Single nucleotide polymorphism association and haplotype analysis were performed. Results: The frequency of G allele of rs6119954 was significantly higher in patients than that in controls (P = 0.017). Genotype distribution of rs6119954 was significantly different between patients and controls (P = 0.046). A haplotype-wise analysis revealed a higher frequency of the T-G (rs2424908–rs6119954) haplotype in patients than that in controls (P = 0.033). In the transmission disequilibrium test analysis, G allele of rs6119954 was preferentially transmitted in the trios (P = 0.030). Conclusion: Our findings indicate that DNMT3B may be a candidate gene for susceptibility to early onset schizophrenia.     

Support for the involvement of the ERBB4 gene in schizophrenia: A genetic association analysis

Cellular, animal and human studies support the involvement of aberrant NRG–ErbB signaling in the pathogenesis of schizophrenia. The aim of the present study was to examine whether genetic variation in the human ERBB4 gene is associated with susceptibility to schizophrenia. Two hundred and twenty-seven unrelated chronic inpatients with schizophrenia were enrolled in the study, and the genetic variation in the polymorphisms of the ERBB4 gene in the patients was compared with that of the control group, which consisted of 223 subjects free of psychiatric illness. The results showed that one coding-synonymous polymorphism (rs3748962, Val1065Val) was in genotypic (p = 0.0027) and allelic (p = 0.0007) association with schizophrenia. In comparison with subjects of the rs3748962-TT type, those of the rs3748962-CT and rs3748962-CC types were at 1.74- and 2.64-fold greater risk of schizophrenia (CT vs. TT: OR = 1.71 (95% CI = 1.15–2.53), p = 0.0014; CC vs. TT: OR = 2.64 (95% CI = 1.37–5.23), p = 0.0047), which supports the hypothesis of an additive model of transmission (p = 0.0006). Furthermore, the frequency of haplotype ATC of rs3791709–rs2289086–rs3748962 was found to be significantly higher in the patients with schizophrenia than in the controls (case vs. control = 36.0% vs. 24.4%, permutation p-value = 0.0002). The findings support the involvement of the ERBB4 gene in schizophrenia in Han Chinese.     

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.     

Association study on the NAPG gene and bipolar disorder in the Chinese Han population

Background: Bipolar disorder is a mental health problem throughout the world. Chromosome 18p11 has been identified by several studies as a susceptiblilty region for bipolar disorder and NAPG, located on 18p11, has been suggested as being associated with bipolar disorder in European population. Methods: Our study employed five SNPs (rs2290279, rs495484, rs510110, rs617040 and rs473938) to investigate the role of NAPG in the Chinese Han population based on a sample of 465 controls vs. 499 bipolar patients. Results: Rs617040 was excluded from further analysis because of deviation from Hardy–Weinberg equilibrium. Rs473938 and rs2290279 showed significant association in both allele and genotype frequencies (rs473938: allele p = 0.0028 after 100,000 permutations, genotype p = 0.0018; rs2290279: allele p = 0.0042 after 100,000 permutations, genotype p = 0.0028). Several combinations of haplotype were found to be associated with bipolar disorder. Haplotype T–A–T of rs473938–rs2290279–rs495484 was defined by confidence intervals algorithm and had a p value of 0.0038 after 100,000 permutations. Conclusions: Our study supports NAPG as a candidate for susceptibility to bipolar disorder.     

Contribution of syntaxin 1A to the genetic susceptibility to migraine: A case–control association study in the Spanish population

Migraine is a common neurological disorder with a complex inheritance pattern. Mutations in genes encoding proteins that are involved in ion transport across the neuronal membrane have been linked to rare monogenic variants of migraine. These or other related genes and proteins are also candidates to be involved in the inherited predisposition to the more common forms of migraine without aura (MO) or migraine with aura (MA). One of these proteins, syntaxin 1A, encoded by the STX1A gene, is a key molecule in ion channel regulation and synaptic exocytosis. We assessed the contribution of STX1A to migraine by analyzing three SNPs that cover the entire gene (rs6951030–rs941298–rs4363087), in a case–control association study in 210 migraine patients (102 MO, 86 MA, 22 hemiplegic migraine) and 210 sex-matched unrelated controls. The single-marker analysis revealed significant differences in both allele frequencies (P = 0.0087, OR = 1.48) and genotype distributions (P = 0.0133) of the rs941298 SNP between migraineurs and controls, with an overrepresentation of T-allele carriers in the migraine sample (OR = 1.78). We subsequently performed a haplotype-based analysis and observed evidence of an overrepresentation of the A–T–G (rs6951030–rs941298–rs4363087) allelic combination in migraine patients and an increased frequency of carriers of this risk haplotype (P = 0.008, OR = 1.71). These differences remained significant when patients were subdivided into MO and MA. When the control series was enlarged for rs941298, we confirmed the association only with the whole migraine group.     

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.     

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.     

Association analysis of Neuregulin 1 candidate regions in schizophrenia and bipolar disorder

Schizophrenia (SCZ) and bipolar disorder (BPD) are severe heritable psychiatric disorders involving a complex genetic aetiology. Neuregulin 1 (NRG1) is a leading candidate gene for SCZ, and has recently been implicated in BPD. We previously reported association of two NRG1 haplotypes with SCZ and BPD in a Scottish case–control sample. One haplotype is located at the 5′ end of the gene (region A), and the other is located at the 3′ end (region B). Here, association to haplotypes within regions A and B was assessed in patients with SCZ and BPD in a second Scottish case–control sample and in the two Scottish samples combined. Association to region B was also assessed in patients with SCZ and BPD in a German case–control sample, and in all three samples combined. No evidence was found for association in the new samples when analysed individually; however, in the joint analysis of the two Scottish samples, a region B haplotype comprising two SNPs (rs6988339 and rs3757930) was associated with SCZ and the combined case group (SCZ: p = 0.0037, OR = 1.3, 95% CI: 1.1–1.6; BPD + SCZ: p = 0.0080, OR = 1.2, 95% CI: 1.1–1.5), with these associations withstanding multiple testing correction at the single-test level (SCZ: p_st = 0.022; BPD + SCZ: p_st = 0.044). This study supports the involvement of NRG1 variants in the less well studied 3′ region in conferring susceptibility to SCZ and BPD in the Scottish population.     

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.     

Evidence for transmission disequilibrium at the DAOA gene locus in a schizophrenia family sample

Recently, the DAOA gene locus on chromosome 13q32–q34 has been implicated in the etiology of schizophrenia. We genotyped three single-nucleotide polymorphisms (SNPs: rs778294, rs779293 and rs3918342) in this region in 126 Chinese family trios. In this study, we have identified statistically significant transmission disequilibrium in two markers rs778293 (P = 0.01) and rs3918342 (P = 0.02), and a highly significant under-transmission between haplotype CAT (P = 0.0005) and schizophrenia. The results provide further evidence to support that DAOA gene locus is involved in conferring susceptibility to schizophrenia.     

Meta-analysis of FKBP5 gene polymorphisms association with treatment response in patients with mood disorders

The aim of our study was to assess the association between FKBP5 gene polymorphisms and treatment response in patients with mood disorders using a meta-analysis. Eight separate studies that included data from 2199 subjects were identified. Meta-analysis was performed for three FKBP5 gene polymorphisms (rs1360780, rs3800373, and rs4713916). A significant association of FKBP5 gene rs4713916 polymorphism and response rate was found in patients with mood disorders (Overall: A versus G: OR = 1.28, 95%CI = 1.06–1.53, P = 0.01; GA + AA versus GG: OR = 1.32, 95%CI = 1.05–1.67, P = 0.02. Caucasian: A versus G: OR = 1.28, 95%CI = 1.06–1.55, P = 0.01; GA + AA versus GG: OR = 1.33, 95%CI = 1.04–1.70, P = 0.02). However, we did not detect the association between FKBP5 gene rs1360780 and rs3800373 polymorphisms and treatment response in patients with mood disorders (P > 0.05). This meta-analysis demonstrates that treatment response in patients with mood disorders is associated with FKBP5 gene rs4713916 polymorphism, but not rs1360780 and rs3800373.     

−1722T/C polymorphism (rs733618) of CTLA-4 significantly associated with systemic lupus erythematosus (SLE): A comprehensive meta-analysis

This study was to determine whether −318C/T (rs5742909), −1722T/C (rs733618) and −1661A/G (rs4553808) of Cytotoxic T-lymphocyte antigen-4 (CTLA-4) are associated with systemic lupus erythematosus (SLE). The meta-analysis for −318C/T (rs5742909) included 1163 cases and 1520 controls, for −1722T/C (rs733618) included 1016 cases and 1078 controls, and for −1661A/G (rs4553808) included 637 cases and 774 controls. For −318C/T (rs5742909), statistically significant differences were not noted between cases and controls {fixed/random: OR: 1.103, 95% CI: (0.907–1.341), p = 0.326}. For −1661A/G (rs4553808), also no significant difference existed {fixed: OR: 1.024, 95% CI: (0.843–1.244), p = 0.812; random: OR: 1.077, 95% CI: (0.780–1.300), p = 0.958}. But −1722T/C (rs733618) was significantly associated with SLE both in allele {fixed: OR: 0.699, 95% CI: (0.602–0.811), p = 0.000; random: OR: 0.748, 95% CI: (0.565–0.990), p = 0.042} and in genotype {CC/(CT + TT)} meta-analysis {OR: 0.422, 95% CI: (0.297–0.598), p = 0.000}. Also, we subdivided the −1722T/C group (rs733618) into Asia and Mixed subgroups, in Asia subgroup, the SNP was significantly associated with SLE {fixed: OR: 0.628, 95% CI: (0.528–0.746), p = 0.000; random: OR: 0.641, 95% CI: (0.470–0.875), p = 0.005}, in the Mixed subgroup, this polymorphism was not associated with SLE {fixed: OR: 0.946, 95% CI: (0.707–1.267), p = 0.711; random: OR: 0.973, 95% CI: (0.606–1.560), p = 0.908}. These results suggest that there is evidence of association between the CLTA-4 and SLE, especially −1722T/C polymorphism (rs733618).     

Genetic variants of IL-6 and its receptor are not associated with schizophrenia in Taiwan

The pathophysiological process of schizophrenia is still unclear. The levels of interleukine-6 (IL-6) and its receptor, soluble IL-6R, have been reported to be elevated in the plasma and cerebrospinal fluid of schizophrenic patients. In this study, we tested the association of genetic variants of IL-6 and IL-6R with schizophrenia. Genotyping of three single nucleotide polymorphisms (SNP) for each IL-6 (IL-6-1, IL-6-2, and IL-6-3) and IL-6R (rs4845617 = IL-6R1, rs4553185 = IL-6R2, and rs4379670 = IL-6R3) gene was performed in 100 patients with schizophrenia and 113 normal controls. The polymorphisms of IL-6R2 were genotyped using Tetra-primer ARMS PCR. IL-6R3 polymorphisms were genotyped using restriction fragment length polymorphism (RFLP) with Apo I enzyme as the restriction enzyme. All other polymorphisms were genotyped using the direct sequencing method. We found a di-nucleotide haplotype block and a tri-nucleotide haplotype block in the genes of IL-6 and IL-6R, respectively. All six SNPs and their haplotypes failed to show a significant association with schizophrenia. The IL-6-2 SNP showed a nominally significant association with the positive symptoms of schizophrenia (p = 0.0472). We conclude that the genetic variants of IL-6 and IL-6R are not associated with schizophrenia. In order to verify this result, further study using a larger sample size and exploring the association between the genotype of IL-6-2 and plasma level of IL-6 is recommended.     

TYK2 rs34536443 polymorphism is associated with a decreased susceptibility to endometriosis-related infertility

Introduction

Tyrosine kinase 2 gene (TYK2) is part of the janus kinase (JAK) that binds to the type I interferon-α receptor (IFNAR) on the cell surface of IFN-producing cells, and have crucial importance in the etiology of autoimmune and inflammatory diseases. Many polymorphisms of the TYK2 gene have been identified, and recently, a number of case–control studies were conducted to investigate the association of these polymorphisms with autoimmune and inflammatory diseases, with conflicting results. Based on these observations, we hypothesized that the TYK2 polymorphisms (rs34536443, rs2304256, rs280523, rs12720270 and rs12720356) might be involved in the pathogenesis of endometriosis and/or infertility.

Methods

Genetic association study comprising 275 infertile women with endometriosis, 92 women with idiopathic infertility and 307 fertile women as controls. TYK2 polymorphisms were identified by TaqMan PCR. Genotype distribution, allele frequency and haplotype analysis of the TYK2 polymorphisms were performed. A p-value <0.05 was considered significant.

Results

Single-marker analysis revealed that TYK2 rs34536443 was significantly associated with protection against endometriosis-related infertility, especially in moderate/severe disease (p = 0.002; OR = 0.24, 95% IC = 0.09–0.62). No difference was found considering the infertile group without endometriosis. No associations were found considering rs2304256, rs280523, rs12720270 and rs12720356 either for endometriosis-related infertility group or idiopathic infertility group. Haplotype analysis of five TYK2 polymorphisms identified a haplotype “CTATG” associated with protection against endometriosis-related infertility, especially in moderate/severe disease (p = 0.027).

Conclusion

This is the first study to report an association between TYK2 polymorphisms and endometriosis and/or infertility. These findings require replication in other populations but suggest the TYK2 rs34536443 polymorphisms and “CTATG” haplotype can be associated with a decreased susceptibility to endometriosis-related infertility in Brazilian women.     

Association of GPR50, an X-linked orphan G protein-coupled receptor,and affective disorder in an independent sample of the Scottish population

A recent report detected association between GPR50, an orphan G protein-coupled receptor, and bipolar disorder (BD) in the Scottish population [29]. We sought to replicate this study in a second sample from the same population, consisting of 338 patients with BD, 359 patients with major depressive disorder (MDD) and 913 control individuals. In addition, the effect of GPR50 genotype on clinical phenotype and treatment response was assessed in a subset of 56 patients with early onset MDD (eoMDD). We identified an association with BD in women with an intronic SNP, rs1202874, that withstood correction for multiple testing (p = 0.0035, permuted p = 0.037, OR = 1.9, 95%CI 1.2–3.0). However, we failed to find an association with the previously associated Δ502-505 polymorphism (p = 0.2). Combined analysis of this and the original samples did detect association between the deletion and susceptibility to BD in females, but with a reduced effect size (p = 0.0006, permuted p = 0.0024, OR = 1.41, 95%CI 1.16–1.71). In the highly phenotyped eoMDD subgroup, we found an association between the Δ502-505 deletion polymorphism and age of onset (p = 0.049), number of episodes (p = 0.044), hypomanic symptoms (p = 0.019), and initial thinking time (p = 0.027), in women; and in family history of depression in men (p = 0.038), uncorrected for multiple testing. No association was seen between Δ502-505 genotype and treatment response at 3 months. To our knowledge this is the first association of rs1202874 with BD and is the second positive association at the GPR50 locus.     

Association of functional variants in the dopamine D2-like receptors with risk for gambling behaviour in healthy Caucasian subjects

Pathological gambling (PG) is an impulse control disorder with suggestive genetic vulnerability component. We evaluated the association of genetic variants in the dopaminergic receptor genes (DRD1-3s) with risk for gambling in healthy subjects using the Canadian Problem Gambling Index (CPGI). Healthy Caucasian subjects who had gambled at least once in their lifetime (n = 242) were included in the analysis. Gender was not associated with the CPGI, while younger age was associated with higher CPGI scores. We have found that none of the single polymorphisms investigated on DRD1 and DRD3 were associated with CPGI scores in healthy subjects. However, we observed trends for association on the TaqIA/rs1800497 polymorphism (P = 0.10) and the haplotype flanking DRD2 (G/C/A rs11604671/rs4938015/rs2303380; P = 0.06). Both trends were associated with lower CPGI score. Our results provide further evidence for the role of dopamine D2-like receptor in addiction susceptibility.     

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.