HLA-C and KIR genes in hepatitis C virus infection

Natural killer (NK) cells are key components of the innate antiviral immune response. NK cell function is regulated by the interaction of major histocompatibility complex class I molecules with NK inhibitory receptors. The aim of this study was to investigate the role of the HLA-C/KIR pair in hepatitis C virus clearance in our population. A total of 196 hepatitis C virus-infected patients (65 resolved and 131 with persistent infection) were included in the study. Genotyping of HLA-C was carried out using polymerase chain reaction followed by a reverse sequence-specific oligonucleotide probe detection system. NK receptor-specific polymerase chain reaction typing of KIR2DL1, KIR2DL2, and KIR2DL3 was performed on the same patient group. Frequencies of the KIR2DL2 gene and the KIR2DL2/KIR2DL2 genotype were lower among patients with persistent infection (32.3% vs 45.4% among resolved, P = 0.01, OR = 0.57, 95% CI = 0.36-0.91; and 16.2% vs 32.3% among resolved, P = 0.02, OR = 0.41, 95% CI = 0.19-0.87). Nevertheless, the frequency of the KIR2DL3 gene was higher among patients with persistent infection (66.9% vs 54.6% among resolved P = 0.02, OR = 1.68, 95% CI = 1.07-2.65). Trends toward lower frequencies of the HLA-C2C2 genotype and NK-HLA interactions with strong and moderate affinity among the patients with persistent infection were also observed.     

Mannose-binding lectin gene polymorphisms are not associated with susceptibility to hepatitis C virus infection in the Brazilian Amazon region

The present study compares the genotype frequencies between two population groups composed by 73 hepatitis C virus (HCV)-infected patients and 92 seronegative controls and investigates the role of allele variants as a possible factor in the susceptibility to HCV infection and the influence on disease progression. The identification of MBL*B and MBL*C alleles was performed by restriction fragment length polymorphism analysis of the 349-bp product using BanI and MboII restriction enzymes, respectively, and a polymerase chain reaction–sequence-specific polymorphism for discrimination of MBL*D. The analysis of allele and genotype frequencies between an HCV-infected group and seronegative controls did not indicate significant differences. The comparison of chronically infected subjects with and without liver cirrhosis was also not statistically significant. The odds ratio estimations were not significant, and the values obtained cannot suggest that the presence of allele variant MBL*B could have some influence in the risk of HCV infection progression to liver cirrhosis and that the presence of allele MBL*D could confer some protection against disease progression, but a larger sample size is necessary to confirm the present results.     

HLA-DPB1 and HLA-C alleles are associated with leprosy in a Brazilian population

Despite intense efforts, the number of new cases of leprosy has remained significantly high over the past 20 years. Host genetic background is strongly linked to the pathogenesis of this disease, which is caused by Mycobacterium leprae (M. leprae), and there is a consensus that the most significant genetic association with leprosy is attributed to the major histocompatibility complex (MHC). Here, we investigated the association of human leukocyte antigen (HLA) class I and II genes with leprosy in a Brazilian population encompassing 826 individuals from a hyperendemic area of Brazil; HLA typing of class I (-A, -B, -C) and class II (-DRB1, -DQA1, -DQB1, -DPA1, and -DPB1) loci was conducted. Initially, the associations were tested using the chi-square test, with p-values adjusted using the false discovery rate (FDR) method. Next, statistically significant signals of the associations were submitted to logistic regression analyses to adjust for sex and molecular ancestry data. The results showed that HLA-C*08, -DPB1*04, and -DPB1*18 were associated with protective effects, while HLA-C*12 and -DPB1*105 were associated with susceptibility to leprosy. Thus, our findings reveal new associations between leprosy and the HLA-DPB1 locus and confirm previous associations between the HLA-C locus and leprosy.     

ERAP,KIR and HLA-C gene interaction in susceptibility to recurrent spontaneous abortion in the Polish population

Endoplasmic reticulum aminopeptidases ERAP1 and ERAP2 trim peptides to generate stable antigenic epitopes for their presentation by HLA class I (HLA-I) molecules to T cell receptor. By influencing the peptide repertoire of HLA-I molecules, they affect also the interactions of HLA-I with killer cell immunoglobulin-like receptors (KIRs) of natural killer (NK) cells. HLA-C is the only polymorphic HLA-I molecule present on the trophoblast.In this study we investigated the role of ERAP1 and ERAP2 polymorphisms in the context of KIR and HLA-C genes in women suffering from recurrent spontaneous abortion (RSA) in the Polish population. We used TaqMan genotyping assays for ERAP1 rs27044, rs30187, rs2287987, rs26618, rs2665 and ERAP2 rs2248374; PCR-SSP methods for KIR and HLA-C genotyping. We tested 285 women who experienced recurrent spontaneous abortion (RSA) and 319 fertile women.We observed a significant association of ERAP1 rs30187TT genotype with RSA (p = 0.02, OR = 1.89, 95%CI = 1.11–3.21), however the most striking association was found in comparison of patients and controls with ERAP1 rs30187TT and KIR Bx genotypes (p = 0.006, p_corr. = 0.036, OR = 2.40, 95%CI = 1.27–4.52). Moreover, this effect was even stronger in HLA-C2 positive patients (p = 0.0031, p_corr. = 0.019, OR = 3.46, 95%CI = 1.48–8.11). Other weaker associations of the remaining tested ERAP single nucleotide polymorphisms with RSA were also presented.In conclusion, ERAP1 rs30187TT genotype itself increased susceptibility to RSA but this effect was much stronger in patients positive for HLA-C2 and KIR Bx genotypes.     

MASP2 gene polymorphism is associated with susceptibility to hepatitis C virus infection

Hepatitis C virus (HCV) has become a major public health issue and is prevalent in most countries. We examined several MASP2 functional polymorphisms in 104 Brazilian patients with moderate and severe chronic hepatitis C using the primers set to amplify the region encoding the first domain (CUB1), a critical region for the formation of functional mannan-binding lectin (MBL)/MBL-associated serine proteases (MASP)-2 complexes, and the fifth domain (CCP2), which is essential for C4 cleavage of the MASP2 gene. We identified five single nucleotide polymorphisms in patients and controls: p. R99Q, p. D120G, p.P126L, p.D371Y, and p.V377A. Our results show that the p.D371Y variant (c.1111 G > T) is associated with susceptibility to HCV infection (p = 0.003, odds ratio = 6.33, 95% confidence interval = 1.85-21.70). Considered as a dominant function for the T allele, this variant is associated with high plasma levels of the MASP-2 in hepatitis C patients (p < 0.001). However, further functional investigations are necessary to understand the degree of involvement between MASP2 and the HCV susceptibility.     

Interleukin 12B gene polymorphism and apparent resistance to hepatitis C virus infection

Cellular immunity with interferon gamma production could have a role in protection from hepatitis C virus (HCV). Interleukin (IL)-12 is a key cytokine in promoting such anti-viral T helper 1 (Th1) responses. We hypothesized that a genetic background able to promote cellular responses may be associated with apparent protection from infection and have investigated the distribution of the functional 1188A/C polymorphism of IL-12B in HCV exposed but uninfected cases. The frequency of the high IL-12-producing C allele was determined by restriction enzyme genotyping in 76 exposed-uninfected individuals and 105 healthy controls. Overall, the C allele was found in 27.6% of exposed-uninfected cases compared with 16.7% of healthy controls [chi(2) = 6.3, P = 0.02, odds ratio (OR) = 1.9, 95% confidence interval (CI) = 1.1-3.2]. CC genotype was found in 10.5% of exposed-uninfected cases compared with 0.9% controls (chi(2) = 9.3, P = 0.01, OR = 12, 95% CI = 1.5-100). Individuals at high risk of HCV infection yet who remain uninfected may be resistant in some way to infection. In our cohort of exposed-uninfected cases a genetic background of enhanced IL-12 production was associated with apparent resistance to HCV infection. This lends support to a central role for cellular immune responses in protecting from infection.     

HLA-C1 ligands are associated with increased susceptibility to systemic lupus erythematosus

Recently, the role of killer cell immunoglobulin-like receptor (KIR) in autoimmune diseases has received increasing attention. The present study was undertaken to determine the association of KIR genes and the human leukocytes antigen (HLA) ligands with Systemic Lupus Erythematosus (SLE) and accompanying oxidative stress. Presence or absence of 17 KIR and 5 HLA loci was performed using the polymerase chain reaction-sequence specific primer (PCR-SSP) method by case-control study. A total of 45 SLE patients, and 60 healthy controls, all of Sicilian descent, were enrolled. Plasma values of the anti-oxidant molecule Taurine were determined in all subjects by capillary electrophoresis UV detection. The carrier frequency of the KIR2DS2 gene was significantly increased in SLE patients compared to healthy controls (73.3 versus 45.0%; OR?=?3.36; 95% CI?=?1.46–7.74; p?=?.005) suggesting a role of KIR2DS2 gene in the susceptibility to disease. We also observed a strong positive association between the presence of HLA-C1 ligands group and the disease (82.2% in SLE patients versus 41.7% in controls; OR?=?6.47, 95% CI?=?2.58–16.26; p?<?.0001). Stepwise logistic regression analysis supported the effect of the HLA-C1 ligands in SLE patients (OR?=?7.06, 95% CI?=?0.07–2.19; p?=?.002), while the KIR genes were no longer significant. Interestingly, we found that SLE patients HLA-C1 positive showed significantly decreased plasma levels of antioxidant activity marker Taurine (69.38?±?28.49?μmol/L) compared to SLE patients HLA-C1 negative (108.37?±?86.09?μmol/L) (p?=?.03). In conclusion, HLA-C1 ligands group was significantly associated with an increased risk of SLE as well as an increased oxidative stress status overall in SLE patients.     

High prevalence of GB-C/hepatitis G virus in a Brazilian population with helminth infection

A study of GB-C virus/Hepatitis G virus (GBV-C/HGV) infection was carried out in a rural population of Northeastern Brazil, in which the prevalence of schistosomiasis is 80–90%. Despite the absence of parenteral risk exposure, the prevalence of GBV-C/HGV markers of infection was found to be unusually increased: viremia, 16.4%; specific antibody, 18.3%. It is therefore suspected that helminth infection influenced the immune response to GBV-C/HGV infection by shifting the balance of cytokine responses from Th1 to Th2, resulting in a delayed viral clearance. Phylogenetic analysis of viral isolates did not provide evidence for high rates of sexual or mother-to-infant viral transmission. The study revealed that viral strains belonged to types 1 and 2 only (predominant in Africa and Europe, respectively), suggesting that GBV-C/HGV was introduced into the New World by white conquerors and black slaves since the 16th century. J. Med. Virol. 56:310–315, 1998 . © 1998 Wiley-Liss, Inc.     

Association of a TANK gene polymorphism with outcomes of hepatitis B virus infection in a Chinese Han population

The host genetic compound plays a vital role in determining clinical outcomes of hepatitis B virus (HBV) infection. The tumor necrosis factor receptor-associated factor family member-associated nuclear factor-κB (NF-κB) activator (TANK) takes part in the tumor necrosis factor-α (TNF-α)-mediated NF-κB signaling pathway and the interferon (IFN)-induction pathways that have relevance to HBV-related liver disease. In this report, we explored whether the intronic polymorphism rs3820998 of the TANK gene was associated with outcomes of HBV infection by binary logistic regression analysis. A total of 1305 unrelated Han Chinese patients recruited from Wuhan, including 180 acute-on-chronic hepatitis B liver failure (ACLF-HBV) patients, 331 HBV-related liver cirrhosis (LC) patients, 308 HBV-related hepatocellular carcinoma (HCC) patients, and 486 asymptomatic HBV carriers (AsC) were genotyped using the TaqMan probe method. Logistic analysis revealed that the single-nucleotide polymorphism (SNP) rs3820998 was significantly associated with susceptibility to ACLF-HBV (dominant model, OR 0.643, 95% CI 0.428,0.964, p=0.033; additive model, OR 0.640, 95% CI 0.414,0.990, p=0.045), and LC (recessive model, OR 0.398, 95% CI 0.164,0.966, p=0.042; additive model, OR 0.379, 95% CI 0.155,0.928, p=0.034). These results indicate that the G > T variant is a protective factor in the development of ACLF-HBV and LC, and that the SNP rs3820998 in the TANK gene may play a role in mediating susceptibility to ACLF-HBV and LC in a Chinese Han population.     

Polymorphisms of killer cell immunoglobulin-like receptor gene: possible association with susceptibility to or clearance of hepatitis B virus infection in Chinese Han population

Aim

To explore whether killer cell immunoglobulin-like receptors (KIR) gene polymorphisms are associated with susceptibility to persistent hepatitis B virus (HBV) infection or HBV clearance.

Methods

Fifteen known KIR genes were determined in 150 chronic hepatitis B patients, 251 spontaneously recovered controls, and 412 healthy controls by the sequence specific primer polymerase chain reaction (SSP-PCR) method. KIR genotype frequency (gf) differences were tested for significance by two-tailed Fisher exact test or χ² test. Multifactorial analysis was also performed by logistic analysis (the SAS system).

Results

Framework genes KIR2DL4, KIR3DL2, KIR3DL3, and KIRZ were present in all individuals. The frequencies of KIR2DS2 and KIR2DS3 were higher in chronic hepatitis B patients, than in both healthy and spontaneously recovered controls. The frequencies of activating KIR2DS1, KIR3DS1, and the inhibitory KIR2DL5 were higher in spontaneously recovered controls than in chronic hepatitis B patients and healthy controls.

Conclusion

KIR polymorphisms may be associated with susceptibility to HBV infection or HBV clearance. It could be suggested that KIR2DS2 and KIR2DS3 were HBV-susceptive genes, which induced a persistent yet weak inflammatory reaction that resulted in continuous injury of live tissues and chronic hepatitis. KIR2DS1, KIR3DS1, and KIR2DL5, on the other hand, may be protective genes that facilitated the clearance of HBV.Hepatitis B virus (HBV) infection, one of the major viral diseases in the word, especially in China, causes a broad spectrum of liver diseases (1). It has been documented that there are currently about 350 million people with persistent HBV infection worldwide. Persistent HBV infection has been regarded as a multi-factorial disorder relevant to virus, host age, sex, environment, and concurrent infections with the hepatitis C and D virus, and human immunodeficiency virus (HIV) (2). Segregation analysis and twin studies strongly support the role of host genetic background in determining the course of HBV infection (3-5). Actually, the susceptibility to infectious diseases is governed by a number of different factors, such as cytokine production, antigen presentation, and receptor recognition. Of note, genetic susceptibility to persistent HBV infection or HBV clearance are likely polygenic, pertaining to genes such as the genes of human leukocyte antigen (HLA) and class cytokine receptor.It has been reported that killer cell immunoglobulin-like receptor (KIR) genes present diversity in the Chinese population (6,7). However, it is unknown whether KIR genes participate in the regulation of HBV infectious process. KIR gene family, located on human chromosome 19q13.4, encodes HLA class I receptors expressed by natural killer (NK) cells and subsets of T-cells. KIR genes are organized in a highly polymorphic, multi-gene family with considerable allelic polymorphism. The genes have been divided into distinct groups, depending on the number of external immunoglobulin domains (2D or 3D). The presence of a long cytoplasmatic tail with two immune tyrosine-based inhibitory motifs (ITIM) allows the transduction of inhibitory signals and characterizes the inhibitory KIRs (2DL, 3DL), whereas the presence of short cytoplasmatic tails corresponds to the activating KIR receptors (2DS, 3DS) (8-11). Theoretically, NK cells and T cells activation may be regulated by one of the two following mechanisms: the presence of and signaling through activating receptors on a large proportion of effector cells (ie, KIR haplotypes containing many activating receptors) or the presence of inhibitory receptor-ligand combinations that send relatively poor inhibitory signals. Upon interaction with HLA class I molecules expressed on the surface of target cells, KIR genes provide activating or suppressing signals to regulate the activation of NK cells and T cells, thereby playing an important role in antiviral and anti-tumor immunity (12).Previous studies have demonstrated that KIR genes are involved in the pathogenesis of a variety of diseases, including rheumatoid arthritis, vasculitis (13,14), psoriatic arthritis (15), type 1 diabetes mellitus (16), and hepatitis C virus (17). However up to now, the role of KIR polymorphisms in patients with HBV infection has not been investigated. Therefore, the present study was designed to investigate the KIR gene polymorphisms in a large cohort of 150 chronic hepatitis B patients, 251 spontaneously recovered cases, and 412 healthy controls by means of sequence specific primer polymerase chain reaction (SSP-PCR), with special attention given to the relationship between KIRs and the HBV infection or HBV clearance.     

HLA-G susceptibility to hepatitis B infection and related hepatocellular carcinoma in the Japanese population

AimsHuman leukocyte antigen (HLA)-G plays a role in various physiological immunomodulatory functions. Aberrant HLA-G expression is observed in various disease states, including tumors, autoimmune disorders, and viral infections. The present study investigated the association between HLA-G functional gene polymorphisms (rs1736933 [-486 C > A], rs1049033 [+2018 C > T], 14 bp Insertion [Ins]/Deletion [Del] [+2961 Del > Ins], and rs1063320 [+3142 C > G]) and disease susceptibility, hepatocellular carcinoma (HCC) development, and hepatitis B surface antigen (HBsAg) clearance.MethodsAllele discrimination of the 3 SNPs (-486 C > A, +2018 C > T, +3142 C > G) was determined by a TaqMan 5′ exonuclease assay, while the 14 bp Ins/Del polymorphism was typed by fragment analysis using Genetic Analyzer and GeneMapper software. The above polymorphisms were analyzed for 325 Japanese hepatitis B virus (HBV) patients, 355 Japanese healthy subjects (Controls) as healthy controls, and 799 Japanese hepatitis C virus (HCV) patients as disease controls, respectively.ResultsThe 14 bp Insertion allele was significantly more frequent in HBV patients than Controls (27.1 % vs 20.6 %, odds ratio [OR] 1.43, P = 0.005) but did not differ between HCV patients and Controls. Similar results were found for the rs1063320 G allele (38.9 % vs 26.3 %, OR 1.78, P < 0.001) and the rs1736933 T allele (32.2 % vs 26.9 %, OR 1.29, P = 0.034) between HBV and Controls. The rs1049033 T allele showed a weak but significant association with HCC development in the dominant model (OR 1.95, P = 0.04). Regarding HBsAg clearance, the A allele at rs1736933 was significantly correlated in the recessive model (OR 3.23, P = 0.003).ConclusionsThis study revealed significant associations of HLA-G gene polymorphisms with disease susceptibility, HCC development, and HBsAg clearance in HBV patients.     

Association of PTPN22 gene polymorphisms with chronic hepatitis B virus infection in Chinese Han population

Lymphoid protein tyrosine phosphatase encoded by protein tyrosine phosphatase non-receptor 22 (PTPN22) gene plays an important regulatory role in T- and B-cell activation. This study investigated PTPN22 −1123G/C and intron 16 T/C polymorphisms in 372 patients with chronic hepatitis B virus (HBV) infection, 72 HBV infection resolvers and 273 healthy controls. Genotypic association tests between groups assuming codominant, dominant or log-additive genetic models were performed. In recessive model, PTPN22 −1123G/C genotype GG in healthy controls was more frequent than infection resolvers (P = 0.037, OR = 3.606, 95%CI = 1.079–12.053) and this genotype in HBV patients was more frequent than resolvers although the difference was not significant (P = 0.059). The PTPN22 intron 16 T/C genotype TC in cirrhosis patients was significantly higher than asymptomatic carriers (ASC) in codominant (P = 0.028, OR = 9.792, 95%CI = 1.281–74.832) and overdominant (P = 0.025, OR = 10.142, 95%CI = 1.332–77.214) models. This genotype in hepatocellular carcinoma (HCC) patients was significantly higher than ASC in codominant (P = 0.034, OR = 9.200, 95%CI = 1.176–71.990) and overdominant (P = 0.030, OR = 9.677, 95%CI = 1.241–75.442) models. These findings suggest that PTPN22 polymorphisms may predispose the chronicity or the development of cirrhosis and HCC in HBV infection.     

KIR3DL1+HLA-B Bw4Ile80 and KIR2DS1+HLA-C2 combinations are both associated with ankylosing spondylitis in the Iranian population

Contribution of killer cell immunoglobulin-like receptors (KIR) and their human leucocyte antigen (HLA) class I ligands in the pathogenesis of autoimmune diseases has been shown in several studies. In this study, the possible association of KIR genes, their known HLA ligands and compound KIR/HLA genotypes with ankylosing spondylitis (AS) was assessed. Combined KIR/HLA ligand genotyping was performed by a polymerase chain reaction-sequence-specific primers assay in 35 Iranian patients with AS, and genotypes were compared to those in 200 healthy individuals. The frequencies of telomeric cluster genes KIR2DL5A, KIR2DS1 and KIR3DS1 were significantly increased in AS patient group (P(c) = 0.0082, P(c) = 0.0195 and P(c) = 0.0328, respectively). Conversely, HLA-Bw4 ligand (the presence of one or more -B Bw4(Ile80) , -B Bw4(Thr80) and -A Bw4 epitopes) (P(c) = 0.0004) and HLA-B Bw4(Ile80) (P(c) = 0.053) were less frequent in these patients. Meanwhile, compound KIR/HLA genotype analyses revealed lower frequency of KIR3DL1+HLA-B Bw4(Ile80) (P(c) = 0.0343) and higher frequency of KIR2DS1+HLA-C2 (P(c) = 0.0308) combinations in patients with AS than in controls. In addition, the genotypes iKIR+HLA > aKIR+HLA (P(c) = .0308) and iKIR+HLA > aKIR (P(c) = 0.0258) were statistically less common, and genotypes iKIR+HLA = aKIR+HLA (P(c) = 0.0081) and iKIR+HLA < aKIR (P(c) = 0.077) were more common in patient group. Our findings suggest a role for excessive or inappropriate NK cell activation through 'KIR/HLA' system in AS disease.     

非甲-非戊型慢性病毒性肝炎患者隐匿性HBV感染的研究

目的 观察非甲-非戊型慢性病毒性肝炎患者隐匿性HBV感染的状况,探讨荧光定量聚合酶链反应(FQ-PCR)技术对隐匿性HBV感染的诊断价值.方法 应用FQ-PCR技术对57例非甲-非戊型慢性病毒性肝炎患者进行了血清、肝组织HBV-DNA定量检测,并将肝组织HBV DNA定量水平与肝脏炎症活动度的关系进行了分析.结果 血清、肝组织HBV DrqA定量阳性分别为13例(22.81%)、22例(38.60%).13例血清HBV DNA定量阳性患者其肝组织定量亦均阳性,但9例肝组织HBV DrqA定量阳性患者其血清定量为阴性,差异有统计学意义(P<0.01);同时13例血清与肝组织定量均阳性患者比较.显示肝组织HBV DNA定量水平显著高于血清定量水平[(6.62±1.21)拷贝,gvs.(4.03±1.06)拷贝/ml,(P<0.01)].肝组织HBV DNA水平与肝脏炎症活动度并无相关性,10例G2,7例G3,5例G4患者HB'q DNA定量分别为(6.13±1.65)拷贝/g、(5.92±1.81)拷贝,g、(5.83±1.89)拷贝/g,(P0.05),但HBV DNA定量阳性患者均为活动性肝脏病变.结论 HBV隐匿性感染是部分非甲-非戊型慢性病毒性肝炎患者的病因.单纯检测血清免疫学标志物对HBV感染诊断存在漏诊,对非甲-非戊型慢性病毒性肝炎患者应用FQ-PCR技术开展血清定量尤其是肝组织中HBV DNA定量检测可提高HBV感染的诊断.对隐匿性HBV感染的慢性病毒性肝炎亦应给予有效的抗病毒治疗.     

Association of human platelet antigens polymorphisms with susceptibility to hepatitis C virus infection in Chinese population

Hepatitis C virus (HCV) is a major cause of chronic hepatitis. Previous studies have identified a number of single nucleotide polymorphisms that are associated with HCV infection. Human platelet antigens (HPAs) polymorphisms play an important role in several diseases. Here, we demonstrated the association of the HPA‐2, HPA‐3, HPA‐5 and HPA‐15 polymorphisms with susceptibility to HCV infection in Chinese population. Overall, 118 patients with HCV and 167 controls were genotyped for HPAs. There were no significant differences in the allele and genotype frequency distribution for the HPA‐3, HPA‐5 and HPA‐15 systems between the patients with chronic HCV infection and the healthy controls (p > .05). However, the genotype frequency of HPA‐2aa was significantly lower, while HPA‐2ab/bb was significantly higher in patients than that in the controls (p = .006). The allele frequency of HPA‐2a in patients was significantly lower than that in the control group (p = .005). In contrast, HPA‐2b in patients was significantly higher than that in the control group (p = .005). We conclude that HPA‐2 polymorphism is associated with susceptibility to HCV infection, and individuals carrying the HPA‐2b allele may have a higher risk of HCV infection compared with individuals carrying HPA‐2a.     

Cannabinoid type-1 receptor gene polymorphisms are associated with central obesity in a Southern Brazilian population

The CB1 cannabinoid receptor and its endogenous ligands, the endocannabinoids, are involved in energy balance control, stimulating appetite and increasing body weight in wasting syndromes. Different studies have investigated the relationship between polymorphisms of the cannabinoid receptor 1 (CNR1) gene and obesity with conflicting results. In the present study, we investigated the 1359G/A (rs1049353), 3813A/G (rs12720071) and 4895A/G (rs806368) polymorphisms in the CNR1 gene in a Brazilian population of European descent. To verify the association between these variants and obesity-related traits in this population, 756 individuals were genotyped by PCR-RFLP methods. The 4895G allele was associated with waist to hip ratio (WHR) (P = 0.014; P = 0.042 after Bonferroni correction). An additive effect with the GAA haplotype was associated with WHR (P = 0.028), although this statistical significance disappeared after Bonferroni correction (P = 0.084). No significant association was observed between the genotypes of the 1359G/A and 3813A/G polymorphisms and any of the quantitative variables investigated. Our findings suggest that CNR1 gene polymorphism is associated with central obesity in this Brazilian population of European ancestry.