Association of vitamin D receptor gene polymorphisms with clinical outcomes of dengue virus infection

Vitamin D is known to affect pathogenesis of dengue through modulation of immune responses. Vitamin D exerts its effects through vitamin D receptor (VDR). The functioning of VDR is affected by the gene polymorphisms in the coding (rs2228570) and 3′untranslated region (UTR) (rs1544410, rs7975232 and rs731236). In the present study, VDR gene polymorphisms were investigated in 112 dengue infected patients (83 dengue fever (DF) and 29 dengue hemorrhagic fever cases (DHF)) and 105 apparently healthy controls (HCs) using polymerase chain reaction based restriction fragment length polymorphisms methods. HCs had no documented evidence of symptomatic dengue. Results revealed significantly lower frequency of ‘C’ allele of rs7975232 in all dengue patients (DEN) as compared to HCs [(P corrected (Pc) = 0.014, Odds ratio (OR) 0.51]. The frequency of C/C genotype of rs7975232 was significantly lower in DEN and DF cases compared to HCs (DEN vs. HCs: Pc = 0.0184, OR 0.24; DF cases vs. HCs: Pc = 0.028, OR 0.21). The frequency of T allele of rs2228570 in a dominant mode was significantly higher in DHF cases as compared to DF cases (P = 0.034 OR 2.58). A significantly lower frequency of the haplotype G-C-T (Pc = 0.0135) and higher frequency of the haplotype G-A-T (Pc = 0.000085) was observed in DEN and DF cases as compared to HCs. The results suggest that the 3′UTR haplotypes of VDR gene are differentially associated with risk of symptomatic dengue requiring hospitalization. The ‘T’ allele of rs2228570 polymorphism in a dominant mode of inheritance is associated with DHF.     

Lack of association of vitamin D receptor gene polymorphisms with susceptibility to type 1 diabetes mellitus in the Portuguese population

The vitamin D receptor (VDR) gene is a candidate gene for susceptibility to autoimmune disorders. Association studies of VDR polymorphisms and risk of type 1 diabetes often produced conflicting results in different ethnic backgrounds. The aim of this study was to test for association between common VDR polymorphisms and the genetic susceptibility to type 1 diabetes in the Portuguese population. We genotyped 207 patients with type 1 diabetes and 249 controls for the FokI T>C (rs10735810), BsmI A>G (rs1544410), ApaI G>T (rs7975232), and TaqI C>T (rs731236) single nucleotide polymorphisms by polymerase chain reaction and restriction fragment length polymorphism analysis. The distribution of VDR genotype, allele, and haplotype frequencies did not differ significantly between patients and controls. These data suggest that the single nucleotide polymorphisms of the VDR gene are unlikely to contribute significantly to type 1 diabetes susceptibility in the Portuguese population.     

Association between somatostatin gene polymorphisms and sporadic Alzheimer's disease in Chinese population

Recent evidence has suggested that down-regulation of somatostatin (SST) expression in the human brain during early stages of aging leads to an elevation in the steady-state levels of Aβ and therefore may be involved in Alzheimer's disease (AD) progression. We hypothesized that alterations in the SST gene might alter its expression or function and also play a role in the pathogenesis of sporadic AD (SAD). First, we sequenced the entire SST gene in 25 randomly selected controls and 25 SAD patients and then screened for C/T polymorphisms (rs4988514) in the 3′ un-translated region. We genotyped rs4988514 polymorphisms as well as apolipoprotein ?4 (APOE ?4) status in 309 SAD patients and 276 normal controls with restriction fragment length polymorphism (RFLP) analysis. Results showed that the C allele of the rs4988514 polymorphism had an increased incidence in the SAD group compared to the control group (p = 0.042). In subjects with the APOE ?4 allele, the presence of both the CC genotype and the C allele of this polymorphism were elevated in the SAD group compared to the control group (genotype p = 0.027, allele p = 0.011). In the whole study group, the age, sex, and APOE ?4 adjusted OR for the risk of AD in C allele carriers was 1.313 (95%CI = 1.068–2.234, p = 0.027) whereas within only APOE ?4 allele carriers, the adjusted OR increased to 2.734 (95%CI = 1.236–5.862, p = 0.012). Our results supported the notion that the C allele of the rs4988514 polymorphism may increase the risk for AD in the Chinese population and possibly have additive effect with the APOE ?4 allele.     

Association of the brain-derived neurotrophic factor gene and bipolar disorder with early age of onset in mainland China

Several evidences have suggested that the brain-derived neurotrophic factor (BDNF) gene may be involved in the pathogenesis of bipolar disorder (BPD), but not all studies get the same result. The paper investigated two genetic polymorphisms of BDNF, C-270T and Val66Met, in a case–control design for their association with BPD. Sixty-seven patients of early age of onset and 130 patients of late age of onset were selected for study and 208 healthy individuals were used as controls. No significantly statistical differences of these two polymorphisms were found in genotypes or allele frequencies between either overall patients or late age of onset patients and normal control subjects. However, the frequency of the Val allele of the Val66Met polymorphism was found to have significantly increased in the subgroup patients with early age of onset as compared with the controls (genotype: χ² = 6.602, d.f. = 2, P = 0.037; allele: χ² = 6.223, d.f. = 1, P = 0.015). The study demonstrates that the BDNF C-270T and Val66Met polymorphisms are unlikely to contribute to the genetic predisposition to BPD as a whole. But Val66Met may be associated with susceptibility to the early age of onset subset of the disorder, further studies designed to explore the relationship in a larger population may be warranted.     

Association study of sporadic Parkinson's disease genetic risk factors in patients from Russia by APEX technology

Most patients with Parkinson's disease (PD) have sporadic form of the disease with a multifactorial etiology due to interactions between environmental conditions and the genetic constitution of the individuals. We have analyzed by APEX technology 50 single nucleotide polymorphisms (SNPs) in 19 genes related to cholecystokinin, serotonin, dopamine and opioid neurotransmission. Significant differences in the allele and genotype frequencies between the controls and PD patients were detected for four SNPs from three genes (serotonin 2A receptor (rs6311, P = 0.043), Wolfram syndrome 1 (rs1801211, P = 0.007), proopiomelanocortin (rs28930368, P = 0.026 and rs2071345, P = 0.027) genes). Two SNPs in proopiomelanocortin (POMC) gene were also associated with different clinical forms of PD. Our data suggest that at least three genes involved in neurotransmitter systems may have more specific role in genetic predisposition to PD.     

BsmI, TaqI, ApaI and FokI polymorphisms in the vitamin D receptor (VDR) gene and the risk of osteoporosis: a meta-analysis

A meta-analysis regarding BsmI, TaqI, ApaI and FokI polymorphisms in the vitamin D receptor (VDR) gene and their associations with osteoporosis in females is reported. The meta-analysis involved 14, seven, seven and three studies for BsmI, TaqI, ApaI and FokI polymorphisms, respectively. The studies were association studies with osteoporotic cases and controls free of osteoporosis that provided the genotype distribution of individual cases and controls. For the BsmI polymorphism, the allele contrast b vs. B showed heterogeneity among studies (p< 0.01, I2> 50%) and the random effects (RE) pooled odds ratio (OR) was non-significant: 0.94 [95% confidence interval (CI) 0.63-1.38]. Caucasians, postmenopausal cases and studies with WHO diagnostic criteria showed no association under any genetic contrast. However, in East Asians, the OR for the dominant model [fixed effects OR=0.14 (95% CI 0.04-0.50) and RE OR=0.16 (95% CI 0.03-0.84)] was significant, indicating prevention. Overall, for the TaqI, ApaI and FokI polymorphisms, the allele contrast showed heterogeneity and the pooled RE ORs were non-significant [OR=1.06 (95% CI 0.71-1.60), OR=0.99 (95% CI 0.72-1.37) and OR=1.17 (95% CI 0.76-1.80), respectively]. The allele contrast for Caucasians, East Asians, postmenopausal cases and studies with WHO diagnostic criteria showed no association for TaqI, ApaI, and FokI. The allele contrast of homozygotes, and the recessive and dominant models the results followed the same pattern as the allele contrast. Therefore, the relationship between the VDR polymorphisms and osteoporosis remains an unresolved issue and other probable genetic-environmental risk factors interacting with the above polymorphisms should be investigated.     

Association between promoter polymorphisms in anterior pharynx-defective-1a and sporadic Alzheimer's disease in the North Chinese Han population

Amyloid β-peptide (Aβ) deposition in brain is important in the development of sporadic Alzheimer's disease (SAD) and Aβ is produced through sequential cleaving of amyloid precursor protein (APP) by β-secretase and γ-secrease. Anterior pharynx-defective-1 (APH-1) is an important subunit of the gamma-secretase complex, and its expression level was associated with the activity of γ-secrease. We hypothesized that alterations in the APH-1 promoter region might alter APH-1 expression and the activity of γ-secrease, thus be involved in the SAD process. In the present study, we sequenced APH-1a promoter region in 20 randomly selected controls and 20 SAD patients and detected two polymorphisms which were −980C/G (rs3754048) and −21C/A (rs2275780). Then, we investigated genotypes and allele of these two polymorphisms as well as apolipoprotein ?4 (APOE ?4) status in 256 SAD patients and 276 normal controls with restriction fragment length polymorphisms analysis and sequencing. Results showed the GG genotype and G allele of −980C/G polymorphism were more frequent in the SAD group than that in the controls not only in the whole subjects (genotype P = 0.038, allele P = 0.01 respectively) but also in the APOE ?4 + subjects (genotype P = 0.048, allele P = 0.016 respectively). There was no statistical difference between SAD group and controls regarding to the frequency of alleles and genotypes of −21C/A whenever before or after stratification by APOE ?4. Our results suggest that there is an association between −980C/G and the development of SAD in the Northern Han Chinese population and that allele G may interact synergistically with the APOE ?4 allele to increase the risk of SAD.     

Association between promoter polymorphisms of the nicastrin gene and sporadic Alzheimer's disease in North Chinese Han population

Increasing evidences have shown that nicastrin (NCSTN) plays a crucial role in γ-cleavage of the amyloid precursor protein (APP). Inhibition of NCSTN demonstrated an altered γ-cleavage activity, suggesting its potential implication in developing Alzheimer's disease (AD). We detected the NCSTN gene promoter region in 359 sporadic AD (SAD) patients and 331 controls and found three promoter single nucleotide polymorphisms (SNPs): −1216C/A (rs2147471), −796T/G (rs10752637) and −436C/T (rs1324738). For −1216C/A, there were significant differences in the allele and genotype frequency between AD and control subjects (allele P = 0.031, genotype P = 0.017). The allele and genotype frequencies remained significant before and after APOE?4 stratification. The −1216CC carriers increased 2-fold risk for the development of SAD compared to the carriers with −1216CA and AA genotypes (OR = 2.049, 95%CI = 1.410–2.976, P = 0.000). For −796T/G, there were significant differences in the genotype frequency between SAD and control subjects (P = 0.009). This trend is still obvious in the subjects without APOE?4 allele. The −796GG carriers might decrease the risk compared to the carriers with −796TG and TT genotypes (OR = 0.602, 95%CI = 0.393–0.932, P = 0.022). No significant difference was detected either in genotype or in allele frequencies between SAD and control for −436C/T, even after APOE?4 stratification. The haplotype −1216A/−796G may be a protective factor for SAD (OR = 0.795, 95%CI = 0.636–0.995, P = 0.045). Our investigation suggests that −1216C/A and −796T/G are probably related to the development of SAD.     

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 between haplotype −88G/25G in A2M with Alzheimer's disease

Alpha 2-Macroglobulin gene (A2M) has been recognized as a candidate gene for late-onset Alzheimer's disease (AD), but the association between several polymorphisms in A2M gene and risk for AD remained controversial. Moreover, little is known regarding the effects of polymorphisms in A2M promoter region on AD susceptibility. Our study aimed to detect polymorphisms in A2M promoter region, and then evaluate their relationship to sporadic AD (SAD). One single nucleotide polymorphism (−88A/G) in proximal promoter region was found by sequencing, and further analyzed with an established 25T/G polymorphism in 179 SAD patients and 179 age-gender-matched controls. Allele A in −88A/G polymorphism was more prevalent in cases, with a 1.7-folded risk for SAD (OR = 1.74, 95%CI 1.05–2.91, P = 0.031), while G allele in 25T/G was less prevalent in cases, with a 43% reduced risk for SAD (OR = 0.57, 95%CI 0.36–0.89, P = 0.013). After adjusted the effects of age, gender and APOE?4 allele status in logistic regression model, the protective effects of −88G and 25G on SAD still remained. Individuals who carried haplotype −88G/25G had a significant 44% reduced risk for SAD compared to those who did not carry (OR = 0.56, 95%CI 0.34–0.94, P = 0.027), while haplotype −88A/25T carriers had an increased risk for SAD compared to those who did not carry (OR = 1.77, 95%CI 1.06–2.96, P = 0.027). Our study supports that haplotype −88G/25G might play a protective role in the development of SAD, and the protective effects of −88G and 25G were independent of APOE?4 allele.     

Gender differences in the IL6 -174G>C and ESR2 1730G>A polymorphisms and the risk of Parkinson's disease

The −174G>C (rs1800795) single nucleotide polymorphism (SNP) in the promoter of the interleukin-6 (IL6) gene and the 1730G>A (rs4986938) SNP in the estrogen receptor beta (ESR2) may influence the risk of Parkinson's disease (PD). We investigated these SNPs in 380 unrelated US Caucasian PD cases and 522 controls, including 452 individuals of Ashkenazi Jewish (AJ) origin (260 PD, 192 controls). The G allele of the −174G>C SNP was more common in AJ PD cases (p = 0.033) as well as in Non-Jewish (NJ) men with PD (p = 0.022). The GG genotype increased the risk of PD by over two fold in NJ men (OR = 2.11, 95%CI: 1.14-3.89, p = 0.017), and approached significance in the total AJ group with PD (OR = 1.42, 95%CI: 0.97-2.06, p = 0.067). The A allele of the ESR2 1730G>A SNP was associated with a decreased risk for PD in AJ women, and in this group, having the AA genotype decreased the risk of PD by half (OR = 0.45, 95%CI: 0.22-0.92, p = 0.029). Our data supports a role for the IL6 −174G>C G allele in AJ individuals overall. In NJ Caucasians, this role appears to be gender mediated. In both groups, the effect is independent from ESR2 1730G>A. A separate association for the ESR2 1730G>A SNP was found exclusively in women of AJ descent. Other polymorphisms in tight linkage disequilibrium with the SNP differentially influencing expression, ethnic differences in allele distribution, and gender differences in genetic load related to PD, may underlie our findings. Larger studies in diverse populations, including analysis of surrounding regions are recommended.     

The hOGG1 Ser326Cys polymorphism is not associated with sporadic Parkinson's disease

Parkinson's disease (PD) is one of the most common neurodegenerative disorders characterized by progressive and profound loss of dopaminergic neurons in the substantia nigra (SN) resulting in resting tremor, rigidity, bradykinesia, and postural instability. The primary cause of the disease is still unknown, but mitochondrial dysfunction and oxidative stress have been implicated in the neurodegenerative process. Oxoguanine DNA glycosylase (OGG1) removes oxidized guanine (8-oxo-G) from the DNA, thus reducing the mutagenic potential of this modified base. Increased 8-oxo-G levels and up-regulation of OGG1 have been detected in the SN of PD brains. Moreover, studies performed in OGG1 knockout mice revealed the importance of this enzyme in protecting dopaminergic neurons against the accumulation of oxidative DNA damage. A common Ser326Cys polymorphism is known in the human gene encoding OGG1 (hOGG1), and the mutant Cys326 variant has been associated with reduced glycosylase activity. In the present study we screened 139 sporadic PD patients and 211 healthy matched controls for the presence of the hOGG1 Ser326Cys polymorphism. The Cys326 allele frequency was similar between the groups (0.20 in PD patients and 0.19 in controls; p = 0.817), and no difference in genotype frequencies was observed. Moreover, the hOGG1 Ser326Cys polymorphism was not associated with disease age at onset (p = 0.791). Overall, present results suggest that the hOGG1 Ser326Cys polymorphism is not associated with sporadic PD.     

Association study of VDR gene with rheumatoid arthritis in the French population

Vitamin D is a potent regulator of calcium homeostasis and may have immunomodulatory effects. The influence of vitamin D on human autoimmune disease is controversial. The aim of this study was to investigate the role of vitamin D receptor gene (VDR) in rheumatoid arthritis (RA). Three polymorphisms for VDR gene FokI T>C (rs 10735810), BsmI A>G (rs 1544410) and TaqI C>T (rs 731236) were genotyped in 100 RA French nuclear families (set 1) and 100 additional French nuclear families for replication (set 2). The association analysis was performed using comparison of alleles frequencies (AFBAC), transmission disequilibrium test and genotype relative risk. Our results revealed a significant difference of F allele of FokI polymorphism between transmitted and nontransmitted frequencies (P=0.01) in set 1. Furthermore, the F/F genotype was more frequent in RA patients compared to controls (P=0.01) in set 1. The replication in set 2 showed similar patterns of transmission with a nonsignificant association. Association with FokI was found to be significant when the two sets were combined (P=0.006). These data suggest that the F allele and F/F VDR genotype are associated with RA. The mechanisms by which distinct receptor variants might confer disease susceptibility remain to be elucidated.     

−1154G/A and −2578C/A polymorphisms of the vascular endothelial growth factor gene in Tunisian Alzheimer patients in relation to β-amyloid (1–42) and total tau protein

Recent evidences indicate that polymorphisms within the promoter region of the vascular endothelial growth factor (VEGF) gene may elevate the risk for Alzheimer's disease (AD). To further investigate, we have analyzed association between promoter polymorphisms of the VEGF gene in 93 AD patients and age and sex matched 113 controls from Tunisian population. The distribution of genotype and allele frequencies of the VEGF (−2578C/A) and (−1154G/A) polymorphisms did not differ significantly between AD and control groups (p > 0.05). In the subgroup of ApoE ?4 carriers, the −2578A was observed to be significantly higher in the AD patients than in the control individuals. After adjusting the data by gender, age and the ApoE ?4 status using logistic regression, the −2578A allele was found to increase the risk for sporadic AD by 1.7-fold. The present study provides the evidence that the −2578A allele may be associated with the development of AD in the individuals with ApoE ?4 allele. In addition, AD patients carrying the −2578A allele had lower Aβ42 (p = 0.029) levels than those without this allele, particularly in subjects with ApoE ?4 allele.     

DMT1 polymorphism and risk of Parkinson's disease

Growing evidence suggests that iron accumulation in the substantia nigra (SN) is involved in the pathology of Parkinson’s diseases (PD). Divalent metal transporter 1 (DMT1) is an endogenous transporter for ferrous iron, the levels of which are significantly increased in the SN in postmortem PD brains. To study the possible association of DMT1 gene with PD occurrence, one mutation (1303C/A) and two single nucleotide polymorphisms (SNPs) (1254T/C and IVS4 + 44C/A) in DMT1 gene were investigated in 192 PD patients in a Han Chinese population and 193 healthy controls by method of polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Direct sequencing was performed in 10% of the samples to validate the genotyping results. Our results failed to find any significant association between the tested genotypes, alleles or mutation and PD, however, a haplotype (C alleles of 1254T and IVS4 + 44C/A polymorphisms) occurred at greater frequencies in PD subjects compared with that of control (18.2% versus 11.4%, OR = 1.72, 95% CI = 1.15-2.59, P = 0.01). These results suggest that CC haplotype in DMT1 gene is a possible risk factor for PD in this Han 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.     

Different implication of NEDD9 genetic variant in early and late-onset Alzheimer's disease

Alzheimer's disease (AD) is a complex and multifactorial progressive neurodegenerative disease. Recently, two studies reported inconsistent results on a possible involvement of the NEDD9 (neural precursor cell expressed, developmentally down-regulated 9, 6p25-p24) as a candidate gene for the risk of developing AD and/or Parkinson's disease (PD). We analyzed the distribution of the rs760678 SNP polymorphism in 735 Italian subjects: 214 unrelated sporadic late-onset AD patients (LOAD, 64.5% females, mean age-at-onset 71.8 ± 5.2 years), 135 early-onset AD patients (EOAD, 57.3% females, mean age-at-onset 57.5 ± 5.5 years) and 386 healthy controls (68.9% females, mean age 83.4 ± 17.9 years; SD). We observed a statistically significant difference between LOAD patients and controls according to genotypes (P = 0.016) and allele frequency (P = 0.007); CC genotype was more frequent in LOAD cases (44.4%) than controls (36.0%). No difference after stratification of the data in terms of gender and status of the APOE ?4 allele was observed. In conclusion, our data do support an implication of the NEDD9 allelic variant in late-onset AD, with an independent effect of the apolipoprotein E (APOE) ?4 allele in the risk of developing AD.     

The HIF1A rs2057482 polymorphism is associated with risk of developing premature coronary artery disease and with some metabolic and cardiovascular risk factors. The Genetics of Atherosclerotic Disease (GEA) Mexican Study

The aim of the present study was to establish the role of HIF1A gene polymorphisms in the risk of developing premature coronary artery disease (CAD) in a well-characterized clinical cohort. Three polymorphisms in HIF1A (rs11549465, rs11549467, rs2057482) gene were genotyped in 949 patients with premature CAD, and 676 healthy controls (with negative calcium score by computed tomography). Under a dominant model adjusted for age, visceral to subcutaneous adipose tissue (VAT/SAT) ratio, hypertension, type 2 diabetes mellitus (T2DM), HDL-C levels, hypercholesterolemia and hypertriglyceridemia, the rs2057482 T allele was associated with decreased risk of premature CAD when compared to healthy controls (OR = 0.616, P_dom = 0.020). The effect of the studied polymorphisms on various metabolic parameters and cardiovascular risk factors was explored. In this analysis, the rs2057482 T allele was associated with decreased risk of obesity, central obesity, hypertension, hypercholesterolemia, hypertriglyceridemia and increased risk of T2DM. Under a dominant model adjusted by age, the HIF1A rs2057482 T polymorphism was associated with high VAT/SAT ratio (P = 0.009) and HDL-C levels (P = 0.04) in healthy controls. The results suggest that HIF1A rs2057482 polymorphism is involved in the risk of developing CAD and is associated with some metabolic parameters and cardiovascular risk factors.     

The interleukin-6 gene −572C/G promoter polymorphism modifies Alzheimer's risk in APOE ɛ4 carriers

Inflammatory response is involved in the etiopathology of Alzheimer's disease (AD). Interleukin-6 (IL-6), a pleiotropic inflammatory cytokine, was reported to be associated with both increased Aβ aggregation and the appearance of hyperphosphorylated tau in AD brain. To explore the association of genetic variants in the promoter of IL-6 gene with sporadic AD (SAD), a case–control study was conducted in a North Chinese Han population. A systematic screening of IL-6 promoter was performed using direct sequencing and two polymorphisms were obtained including −572C/G (rs1800796) and −384A/T (rs7802308). Definitive genotyping of these markers and apolipoprotein E (APOE) polymorphism were surveyed in 341 SAD patients and 421 controls. The results revealed no significant differences in the distributions of alleles or genotypes between SAD and control groups. However, there was an interaction between −572C/G and APOE genotypes (P = 0.016) using logistic analysis. In the subjects with APOE ?4, there were significant differences in the allele (P = 0.004) and genotype (P = 0.004) distributions of −572C/G polymorphism between SAD and control groups. The −572CC genotype increased risk for AD by 3.301-fold (Wald = 11.093, adjust OR = 3.301, 95% CI = 1.635–6.665, P = 0.001) compared to CG + GG genotype. The present results suggest the −572 polymorphism could modify the risk for SAD in APOE ?4 carriers.