Phosphodiesterase 4D and 5-lipoxygenase activating protein genes and risk of ischemic stroke in Sardinians

Genetic factors contribute to the risk of ischemic stroke (IS). The phosphodiesterase-4D (PDE4D) and the 5-lipoxygenase activating protein (ALOX5AP) genes were identified as contributors to stroke in an Icelandic population. In an attempt to better define the contributory role of PDE4D and ALOX5AP genes to the risk of IS in humans, we carried out the present association study in a well-characterized, earlier published, genetically homogenous population from the island of Sardinia, Italy. In this cohort, including 294 cases and 235 controls, age, hypertension, hypercholesterolemia, and atrial fibrillation represent risk factors for IS. The PDE4D gene was evaluated by four single nucleotide polymorphisms (SNP32, SNP45, SNP83, SNP87) and by the microsatellite AC008818-1; the ALOX5AP gene was characterized by three SNPs (SG13S32, SG13S89, ALO2A). The results of our study provide no evidence of association between any single PDE4D and ALOX5AP gene variant with the risk of IS in the Sardinian cohort. Haplotype analysis, including that constructed with allele 0 of microsatellite AC008818-1 and SNP45 of the PDE4D gene, was also negative. In conclusion, we found no evidence of association between PDE4D and ALOX5AP genes and the risk of IS in a genetically homogenous population from Sardinia.     

No association of ALOX5AP polymorphisms with risk of MRI-defined brain infarcts

The arachidonate 5-lipoxygenase-activating protein (ALOX5AP) gene has been associated with stroke. The majority of the reported ALOX5AP associations have considered non-radiologically confirmed infarcts as the stroke phenotype. We assessed the association of genetic variants in ALOX5AP with stroke defined by the presence of infarcts on brain magnetic resonance imaging (MRI). We studied 202 persons with MRI-defined brain infarcts and 487 healthy individuals of Caribbean Hispanic ancestry. Another sample of European ancestry comprised 1823 persons with MRI-defined brain infarct and 7578 control subjects. Subjects were genotyped for the 4 single nucleotide polymorphisms (SNPs) that define ALOX5AP HapA haplotype. No association was found between SNPs and MRI-defined brain infarcts. Our data do not support the hypothesis that variants in ALOX5AP are associated with risk of MRI-defined brain infarcts.     

Association of ALOX5AP gene single nucleotide polymorphisms and cerebral infarction in the Han population of northern China

ABSTRACT: BACKGROUND: To explore the association of ALOX5AP single nucleotide polymorphisms (SNPs) and haplotype with the occurrence of cerebral infarction in the Han population of northern China. METHODS: Blood samples were collected from 236 patients of Han ancestry with a history of cerebral infarction and 219 healthy subjects of Han ancestry with no history of cerebral infarction or cardiovascular disease. Applied Biosystems(R) TaqMan(R) SNP Genotyping Assays for SNP genotyping were used to determine the genotypes of 7 ALOX5AP SNP alleles (rs4073259, rs4769874, rs9315050, rs9551963, rs10507391, rs9579646, and rs4147064). RESULTS: One SNP allele (A) of rs4073259 was significantly associated with development of cerebral infarction (P = 0.049). In comparison to control groups, haplotype rs9315050&rs9551963 AAAC [OR (95 % CI) =1.53 (1.02-2.29)], and genotypes rs4147064 CT [OR (95 % CI) =1.872 (1.082-3.241)], and rs9551963 AC [OR (95 % CI) = 2.015 (1.165-3.484)] increased the risk of cerebral infarction in patients with hypertension. Genotype rs9579646 GG [OR (95 % CI) = 2.926 (1.18-7.251)] increased the risk of, while rs4073259 GG [OR (95 % CI) = 0.381 (0.157-0.922)] decreased the risk of cerebral infarction in patients with diabetes. CONCLUSION: These results suggest the ALOX5AP SNP A allele in rs4073259 and genotype rs9579646 GG, rs9551963 AC, and haplotype rs9315050 & rs9551963 AAAC were associated with an increased risk of ischemic stroke in the Han population, while rs4073259 GG was associated with a decreased risk.     

The role of LTA4H and ALOX5AP polymorphism in asthma and allergy susceptibility

Background: Leukotrienes (LTs) have been identified as central mediators in asthma and allergy. Pharmacological inhibition of cysteinyl‐LT activity improves asthma symptoms and control. Accumulating evidence suggests a role for the dihydroxy leukotriene LTB₄ in airway disease. LTA₄ hydrolase and 5‐lipoxygenase activating protein have key roles in LTB₄ production. Single nucleotide polymorphism (SNPs) and haplotypes spanning the LTA4H and ALOX5AP genes have been associated with LTB₄ production and myocardial infarction (MI). Objective: To assess the contribution of LTA4H and ALOX5AP polymorphism to asthma and allergy susceptibility. Methods: Three hundred and forty‐one Caucasian families (two asthmatic siblings) were genotyped for eight SNPs spanning ALOX5AP and five SNPs spanning LTA4H. Association analyses of asthma and related phenotypes (total IgE, atopy, bronchial hyper‐responsiveness, FEV₁) were undertaken using the Family Based Association Test. Results: Single point analyses identified association (P < 0.05) between SNPs SG13S114, SG13S89, SG13S41 (ALOX5AP), rs1978331 (LTA4H) and asthma and/or related phenotypes. Haplotype analyses using all LTA4H SNPs identified a single key risk haplotype for the development of asthma (P = 0.006) and related phenotypes (P = 0.042–0.005). Haplotype analyses using all ALOX5AP SNPs identified several asthma and atopy risk and protective haplotypes. There was limited correlation with previously identified MI risk haplotypes in both genes. Carriers of both ALOX5AP SG13S41 and LTA4H rs1978331 alleles had an increased risk of developing asthma (OR 2.17, CI 1.41–3.32). Conclusions: These data provide evidence for the role of SNPs spanning the ALOX5AP and LTA4H genes in asthma and atopy susceptibility in the Caucasian population and support a role for LTB₄ in disease pathogenesis.     

The role of LTA4H and ALOX5AP genes in the risk for asthma in Latinos

Background Leukotrienes play an important role in allergic and inflammatory diseases, but reports on the involvement of arachidonate 5‐lipoxygenase‐activating protein (ALOX5AP) and leukotriene A₄ hydrolase (LTA4H) in asthma have been inconclusive. Objective To determine whether polymorphisms in ALOX5AP and LTA4H genes are risk factors for asthma in two different Latino groups: Mexicans and Puerto Ricans. Methods The LTA4H gene was sequenced in individuals from both groups to identify novel polymorphisms. Single‐nucleotide polymorphisms (SNPs) in the ALOX5AP and LTA4H genes were analysed for associations with asthma and asthma‐related phenotypes in 687 parent–child trios of Mexican and Puerto Rican origin. Results In LTA4H, five previously unknown polymorphisms were identified. Two SNPs within LTA4H (rs17525488 and rs2540493) were protective for asthma in Latinos (P=0.007 and 0.05, respectively). Among the Mexican patients, LTA4H polymorphisms were associated with baseline lung function and IgE levels. For ALOX5AP, the minor allele at SNP rs10507391 was associated with protection from asthma (odds ratio=0.78, P=0.02) and baseline lung function (P=0.018) in Puerto Ricans. A gene–gene interaction was identified between LTA4H (rs17525488) and ALOX5AP (rs10507391), (P=0.003, in the combined sample). Conclusion Our results support the role of LTA4H and ALOX5AP variants as risk factors for asthma in Latino populations. Cite this as: M. Via, A. De Giacomo, H. Corvol, C. Eng, M. A. Seibold, C. Gillett, J. Galanter, S. Sen, H. Tcheurekdjian, R. Chapela, J. R. Rodríguez‐Santana, W. Rodríguez‐Cintrón, S. Thyne, P. C. Avila, S. Choudhry and E. González Burchard on behalf of the Genetics of Asthma in Latino Americans (GALA) Study, Clinical & Experimental Allergy, 2010 (40) 582–589.     

Association between arachidonate 5-lipoxygenase-activating protein (ALOX5AP) and lung function in a Korean population

Arachidonate 5-lipoxygenase-activating protein (ALOX5AP) plays a role in the 5-lipoxygenase (LO) pathway, which includes the LTC(4), LTD(4), LTE(4) and LTB(4). These leukotrienes are known causative factors of asthma, allergy, atopy and cardiovascular diseases. ALOX5AP lacks enzyme activity and acts by helping 5-LO function. In this study, healthy and general subjects who live in rural and urban areas of Korea were tested for the association of ALOX5AP polymorphisms with lung function. Lung function was also estimated by calculating the predicted values for forced expiratory volume in one second (FEV(1) _%PRED) and the proportion of the forced vital capacity exhaled in the first second (FEV(1) /FVC_PRED). The linear regression was adjusted for residence area, gender, age, height and smoking status. The analysis revealed associations between FEV(1) and the single-nucleotide polymorphism (SNP) rs9506352 and the haplotype TCAC (permuted P-value < 0.05). The linkage disequilibrium block that included the significant SNPs overlapped with SNPs that were revealed previously to associate with myocardial infarction and asthma and to affect lung function. This study is the first to demonstrate the association between lung function and ALOX5AP polymorphisms in a healthy and general population.     

Genetic variation in the lipoxygenase pathway and risk of colorectal neoplasia

Arachidonate lipoxygenase (ALOX) enzymes metabolize arachidonic acid to generate potent inflammatory mediators and play an important role in inflammation‐associated diseases. We investigated associations between colorectal cancer risk and polymorphisms in ALOX5, FLAP, ALOX12, and ALOX15, and their interactions with nonsteroidal anti‐inflammatory drug (NSAID) use. We genotyped fifty tagSNPs, one candidate SNP, and two functional promoter variable nucleotide tandem repeat (VNTR) polymorphisms in three US population‐based case‐control studies of colon cancer (1,424 cases/1,780 controls), rectal cancer (583 cases/775 controls), and colorectal adenomas (485 cases/578 controls). Individuals with variant genotypes of the ALOX5 VNTR had a decreased risk of rectal cancer, with the strongest association seen for individuals with one or more alleles of >5 repeats (wild type = 5, OR>5/≥5 = 0.42, 95% CI 0.20–0.92; P = 0.01). Four SNPs in FLAP (rs17239025), ALOX12 (rs2073438), and ALOX15 (rs4796535 and rs2619112) were associated with rectal cancer risk at P ≤ 0.05. One SNP in FLAP (rs12429692) was associated with adenoma risk. A false discovery rate (FDR) was applied to account for false positives due to multiple testing; the ALOX15 associations were noteworthy at 25% FDR. Colorectal neoplasia risk appeared to be modified by NSAID use in individuals with variant alleles in FLAP and ALOX15. One noteworthy interaction (25% FDR) was observed for rectal cancer. Genetic variability in ALOXs may affect risk of colorectal neoplasia, particularly for rectal cancer. Additionally, genetic variability in FLAP and ALOX15 may modify the protective effect of NSAID use against colorectal neoplasia. © 2013 Wiley Periodicals, Inc.     

Genetic variants of TNFSF4 and risk for carotid artery disease and stroke

In two independent human cohorts, the minor allele of SNP rs3850641 in TNFSF4 was significantly more frequent in individuals with myocardial infarction than in controls. In mice, Tnfsf4 expression is associated with increased atherosclerosis. The expression of TNFSF4 in human atherosclerosis and the association between genotype and cerebrovascular disease have not yet been investigated. TNFSF4 messenger RNA (mRNA) levels were significantly higher in human atherosclerotic lesions compared with controls (730 ± 30 vs 330 ± 65 arbitrary units, p < 0.01). TNFSF4 was mainly expressed by macrophages in atherosclerotic lesions. In cell culture, endothelial cells upregulated TNFSF4 in response to tumor necrosis factor alpha (TNF-α; 460 ± 110 vs 133 ± 8 arbitrary units, p < 0.001 after 6 h of stimulation). We analyzed the TNFSF4 gene in 239 patients who had undergone carotid endarterectomy and 138 matching controls from The Biobank of Karolinska Carotid Endarterectomies and Stockholm Heart Epidemiology Program cohorts and 929 patients and 1,382 matching controls from the Sahlgrenska Academy Study on Ischemic Stroke and Case Control Study of Stroke cohorts, limiting inclusion to patients with ischemic stroke. Participants were genotyped for the rs3850641 SNP in TNFSF4. Genotype associations were neither found with TNFSF4 mRNA levels nor with atherosclerosis associated systemic factors or risk for stroke. This study shows that TNFSF4 is expressed on antigen-presenting cells in human carotid atherosclerotic lesions but provides no evidence for an association of TNFSF4 gene variation with the risk for ischemic stroke.     

Analysis of polymorphic variants of <Emphasis Type="Italic">PDE4D</Emphasis> gene in patients with acute stroke from Moldavian population

The risk of the development of ischemic stroke is caused by both genetic predisposition and environmental factors. In recent investigations, the DeCode group discovered polymorphisms in the phosphodiesterase 4D (PDE4D) gene associated with the risk of the development of ischemic stroke. The aim of the present work was to investigate two polymorphisms in the PDE4D gene (SNP41 (rs52312) and SNP87 (rs2910829)) in patients with ischemic stroke and in the control sample from the Moldavian ethnic group. Statistically significant data about the association between ischemic stroke and studied polymorphisms were not detected.     

Association of CXCL1 promoter polymorphism with ischaemic stroke in Korean population

This is a pilot study analysing association of chemokine gene polymorphisms (CXCL1, rs3117604; CXCL2, rs3806792; CCL2, rs2857656 and rs3760396; CCL5, rs2107538) in Korean patients with ischemic stroke (IS) (n = 120) and age‐matched controls (n = 267). The CXCL1 gene and particularly T allele of rs3117604 was associated with IS.     

Phosphodiesterase 4D Gene and Risk of Noncardiogenic Ischemic Stroke in a Korean Population

Recently published studies from different populations provide apparently conflicting evidence on the association between the phosphodiesterase 4D (PDE4D) gene and ischemic stroke. The relationship between a representative PDE4D genotype and ischemic stroke was explored in a case-control study of 205 consecutive Korean patients with noncardiogenic ischemic stroke and 103 healthy controls who were neurologically and radiologically proven to be stroke-free. We selected and genotyped a PDE4D single nucleotide polymorphism (SNP 41, rs152312) as a candidate marker for susceptibility to ischemic stroke because SNP 41 has shown the most significant association with stroke in both a meta-analysis and the original Icelandic study of the PDE4D gene. No significant difference was observed between the cases and controls in the distribution of the PDE4D SNP 41 genotypes. The results from the adjusted conditional logistic regression analysis (adjusted for age, hypertension, diabetes and smoking status) showed no significant association between PDE4D SNP 41 genotypes and an increased risk of noncardiogenic ischemic stroke. The PDE4D gene is not a major risk factor for noncardiogenic ischemic stroke in a Korean population, which supports the recent evidence suggesting that the causative genetic variants of ischemic stroke may differ across populations.     

Association of single-nucleotide polymorphism on chromosome 9 and ischemic stroke in Heilongjiang province in China

There is a significant correlation between ischemic stroke (IS) and chromosome 9. However, its status was uncertain in China’s cold regions. 1920 IS patients, and 1920 healthy individuals were included in the study. Blood samples were collected. The association of SNPs with IS was evaluated by Sequenom, and logistic regression models adjusted for known risk factors of IS were constructed to assess the SNPs’ associations in cases and controls. We found rs1333040 and rs2383207 were associated with IS, compared with primitive genotypes. The genotype CT of rs7027526 has a protective role during IS development, while the effect of the genotype TT is still not clear. These results changed after stratification by age and sex. In conclusion, rs1333040 and rs2383207 SNPs in CDKN2BAS are associated with ischemic stroke in the Chinese Han population. This study confirms the association between 9p21.3 and IS.     

Association of ABCG2 polymorphisms with ischemic stroke in a Chinese population

ATP‐binding cassette, superfamily G, member 2 (ABCG₂) has been shown to play an important role in the development of ischemic stroke in European and African American populations. The aim of the present study is to test the hypothesis that there are associations between ABCG₂ polymorphisms and ischemic stroke risk in a Chinese population. We conducted a case–control study including 967 participants with ischemic stroke and 939 stroke‐free controls. The rs2231137C > T and rs2231142G > T were genotyped using a TaqMan real‐time polymerase chain reaction assay. We found the rs2231137C > T and rs2231142G > T in ABCG₂ were significantly associated with ischemic stroke (sex‐, age‐, BMI‐, SBP‐, DBP‐adjusted OR = 1.252; 95% CI, 1.035–1.515; P‐value = 0.021 and OR = 1.526; 95% CI, 1.085–2.146; P‐value = 0.015, respectively). By haplotype analyses, the haplotype T‐G still had a strongly significant association with ischemic stroke (OR = 0.806; 95% CI, 0.692–0.939; P‐value = 0.00568). Our findings identified the rs2231137C > T and rs2231142G > T polymorphisms of the ABCG₂ as risk factors for ischemic stroke in a Chinese population.     

Relationship between nerve injury-induced protein gene 2 polymorphism and stroke in Chinese Han population

The aim of present study was to investigate the relationship between nerve injury-induced protein 2 (NINJ2) gene polymorphism and stroke in Chinese Han population.Fifty-two patients with large-artery atherosclerosis (LAA) infarction,85 patients with small-artery occlusion lacunar (SAO) infarction,50 patients with intracerebral hemorrhage (ICH) and 66 controls were included.Genotypes and alleles frequencies of the two single nucleotide polymorphisms (SNPs) of NINJ2 among different groups were analyzed and compared.In regard to rs12425791,the frequencies of the AG and AA+AG genotypes of the LAA and SAO groups were significantly higher than those in the control group;the frequency of the A allele of the SAO group was significantly higher than that of the control group.In regard to rs11833579,there were not any significant differences between the case and the control groups.The SNP rs12425791 is significantly associated with ischemic stroke,and the A allele increases the susceptibility to stroke.The SNP rs11833579 is not significantly associated with stroke.     

The CELSR1 polymorphisms rs6007897 and rs4044210 are associated with ischaemic stroke in Chinese Han population

Background: Recently, CELSR1 was identified by genome-wide association studies (GWAS) as a susceptibility gene for ischaemic stroke (IS) in Japanese individuals.

Aim: The goal was to examine whether CELSR1 variants are associated with IS in the Chinese Han population.

Subjects and methods: This study genotyped two single nucleotide polymorphisms (SNPs) of CELSR1, rs6007897 and rs4044210, in a Chinese sample of 569 IS cases and 581 controls and assessed their genotype and allele associations with IS.

Results: The results showed that rs6007897 and rs4044210 variants of CELSR1 were significantly (p?p?Conclusion: Taken together, the present study has proven for the first time that CELSR1 is a susceptibility gene for IS in the Chinese Han population, especially for LAA.     

Two polymorphisms in the TIM‐4 gene are associated with asthma in a Chinese Han population

The gene family of the T cell immunoglobulin and mucin domain (TIM) proteins encodes cell surface receptors that are involved in the regulation of Th1‐ and Th2‐cell‐mediated immunity. TIM‐1 gene has been found to be associated with asthma in several populations. TIM‐4, the natural ligand for TIM‐1, may influence the susceptility to asthma.To investigate the association of the TIM‐4 gene polymorphisms with asthma in a Chinese Han population. Three single nucleotide polymorphisms (SNPs) in TIM‐4 gene, rs6882076, rs12658558 and rs4702747, were genotyped in 551 unrelated asthma patients and 549 healthy controls. We found that two SNPs of the TIM‐4 gene, rs6882076 and rs4702747, were associated with asthma susceptibility in our study population (with P‐values = 0.009 and 0.005 respectively). No association was observed between asthma and rs12658558. Our results suggest that TIM‐4 gene polymorphisms are associated with asthma in a Chinese Han population.     

Interleukin-21 Polymorphism Affects Gene Expression and is Associated with Risk of Ischemic Stroke

There has been more and more evidence to confirm the essential role of inflammatory processes in the development of ischemic stroke. Interleukin-21 (IL-21), the most recently discovered CD132-dependent cytokine, plays a key role in regulating inflammation. The aim of the study was to understand the association between IL-21 polymorphisms and ischemic stroke, and the effects of these polymorphisms on gene expression. Two polymorphisms in IL-21, rs907715G/A and rs4833837A/G, were identified in 278 ischemic stroke patients and 282 healthy controls. Results showed that frequencies of rs907715GA and AA genotypes were significantly increased in cases than in controls (odd ratio (OR)?=?1.49, 95 % confidence interval (CI): 1.01–2.14, P?=?0.042; OR?=?2.21, 95 % CI: 1.38–3.53, P?=?0.001). Similarly, rs907715A allele revealed a positive association with the disease (OR?=?1.52, P?=?0.001). The rs4833837A/G polymorphism did not show any correlation with ischemic stroke. We further evaluated IL-21 messenger RNA (mRNA) and protein levels in peripheral blood mononuclear cells (PBMCs) from subjects carrying different polymorphism genotypes. Results revealed that subjects carrying polymorphic rs907715GA and AA genotypes had significantly higher IL-21 mRNA levels, whereas protein level was increased only in subjects with rs907715AA genotype. Serum level of IL-21 was also significantly elevated in subjects with rs907715AA genotype. These data suggest that IL-21 polymorphism is associated with increased susceptibility to ischemic stroke possibly by upregulating gene expression.     

Evaluation of the relationships of the WBP1L gene with schizophrenia and the general psychopathology scale based on a case–control study

WBP1L is a target of microRNA 137 (miR‐137) and has been considered a candidate gene for schizophrenia (SCZ). To investigate the relationships between WBP1L and SCZ and its related symptom scales, a total of 5,993 Chinese Han subjects, including 2,128 SCZ patients and 3,865 controls, were enrolled. In addition, an independent sample set for replication study including 1,052 SCZ patients and 2,124 controls were also recruited. Thirty‐two tag single nucleotide polymorphisms (SNPs) located within gene region of WBP1L were selected for genotyping and analyzing. The expression quantitative trait loci (eQTL) effects for the targeted SNPs were investigated with gene expression data from multiple human tissues. Rs4147157 (OR = 0.84, p = 1.51 × 10^?5) and rs284854 (OR = 1.14, p = 7.00 × 10^?4) were significantly associated with SCZ disease status and these association signals were replicated in our replication sample. A significant association was identified between rs4147157 and the general (β = ?.66, p = .001) and total (β = ?.8, p = .0042) scores of positive and negative syndrome scale scores in SCZ patients. Both SNPs were significant eQTL for genes around WBP1L in human brain tissues including ARL3 and AS3MT. To conclude, SNPs rs4147157 and rs284854 were associated with SCZ in the Chinese Han population. Additionally, rs4147157 was significantly associated with specific symptom features of SCZ.     

Variants in 9p21 Predicts Severity of Coronary Artery Disease in a Chinese Han Population

Recent genome‐wide association studies identified the common genetic variants in 9p21 were associated with the coronary artery disease (CAD). However, whether this locus could predict the severity of CAD in Chinese Han population is unclear. 499 CAD patients who underwent coronary angiography (CAG) have been enrolled for this study. The single‐nucleotide polymorphisms rs2383207 and rs2383206 in 9p21 were genotyped in 499 CAG cases and 1519 controls in Chinese Han population. The gene dosage of 9p21 was stratified by the degree of vascular lesions and tested for association with the severity of CAD. Rs2383207 and rs2383206 demonstrated significant associations with 2‐vessel and 3‐vessel disease (P = 2.0×10^?3 and 1.9×10^?4, respectively). GG genotypes of rs2383206 occurred higher proportion of left main trunk (LM) disease (P = 6.0×10^?3). GG genotypes of rs2383207 occurred higher proportion of left anterior descending artery disease (LAD) and right CAD (RCA) (P = 2.7×10^?6 and 1.6×10^?4, respectively). The risk allele G of rs2383207 was associated with severity of CAD estimated by the Gensini score (P = 3.6×10^?5). Rs2383207 may strongly influence the development of CAD in Chinese Han population. The gene dosage in 9p21 could predict the severity of CAD.     

A promoter polymorphism (rs3806798) of interleukin‐15 gene is associated with chronic hepatitis B virus infection in the Chinese Han population

This study aimed to investigate the association between the polymorphisms of IL‐15 gene and susceptibility to chronic hepatitis B virus (HBV) infection in the Chinese Han population. A total of 234 patients with chronic HBV infection and 150 age‐ and sex‐matched healthy controls in the Chinese population were enrolled in this case–control study. Genotyping of ten single nucleotide polymorphisms (SNPs) in the IL‐15 gene was carried out via Sequenom MassARRAY system. The association analysis demonstrated that SNP rs3806798 (A/T) had a significant difference in the distribution between patients and healthy controls (P = 0.033). Moreover, a significantly increased risk of HBV infection was found to be associated with IL‐15 rs3806798 A allele among male patients and HBeAg‐negative patients, compared with IL‐15 rs3806798 T allele (P = 0.003; P = 0.046, respectively). Furthermore, haplotype analysis revealed that haplotype ATAGG (rs3806798, rs12508866, rs1519551, rs6819823 and rs2857261, respectively) in block 1 was significantly associated with HBV infection (P = 0.022). In conclusion, we found an association between IL‐15 rs3806798 and the risk of chronic HBV infection in a sample of Chinese Han population.