Southern Chinese Han Population Research Articles

Telomere length associated with the risks of high-risk and ischemic stroke in southern Chinese Han population.

Some previous studies suggested telomere length was associated with the risk of ischemic stroke (IS). The aim of this study was to further confirm the association between relative telomere length (RTL) and risk of IS and to especially explore its correlation with the risk of high-risk stroke population in southern Chinese Han. RTL was determined by using real-time quantitative polymerase chain reaction from 400 ischemic stroke patients, 409 high-risk stroke populations and 399 healthy controls. The correlations between the controls and the risk of high-risk and ischemic stroke were evaluated by using an unconditional logistic regression. IS patients have shown longer RTL than controls (median1.52vs1.11, p60 years) and gender suggested that the first and second tertile of RTL were correlated with the risk of IS in each group when the second tertile was used as a reference. However, the increased risk for high-risk stroke populations were only presented in the first tertile of RTL in the age≤60 years and female groups. the RTL was associated with an increased risk of ischemic stroke, while it elevated the risk of high-risk stroke in some specific subpopulations.

A complex association between ABCA7 genotypes and blood lipid levels in Southern Chinese Han patients of sporadic Alzheimer's disease

Alzheimer's disease (AD) is the most common neurodegenerative disease characterized by progressive cognitive decline. It can be divided into familial AD (FAD) and sporadic AD (SAD) based on the family history. Recently dysregulation of cholesterol homeostasis has been implicated in the development of late-onset AD. ATP-binding cassette transporter A7 (ABCA7) gene, regulating the transport of cholesterol, has been recently identified as a susceptible gene of AD by several large genome-wide association studies. To test the genetic effect of ABCA7 rs3764650 on blood lipid levels in Southern Chinese Han population and investigate the risk factors of SAD, a total of 118 SAD patients and 120 healthy matched controls were recruited and the genotyping in ABCA7 rs3764650 was conducted on the Sequenom MassARRAY iPLEX platform. Meanwhile, the levels of fasting lipid profile and mini-mental state examination (MMSE) scores were tested. There was significant difference in genotype distribution between SAD patients and controls (p=0.001). While the difference of ABCA7 rs3764650 allele distribution between SAD patients and controls was only significant in APOEε4-noncarriers (p=0.039). The association between blood lipid levels and ABCA7 rs3764650 genotypes was influenced by APOEε4 status. In APOEε4-noncarriers of SAD, the total cholesterol (TC) and low density lipoprotein cholesterol (LDL-C) levels in GG genotype group were significantly lower than those in GT and TT genotype groups (all p<0.05). Whereas no significant difference of blood lipid levels was found among three genotypes in APOEε4-carriers of SAD and controls. Additionally, logistic regression analysis showed that lower high-density lipoprotein cholesterol (HDL-C) levels (p=0.015, OR=5.669) and GG genotype (p=0.013, OR=8.318) were positively associated with SAD. Our results suggest that GG genotype of ABCA7 rs3764650 was a risk factor of SAD in Southern Chinese Han population as well as lipid homeostasis.

Exome sequencing identified a novel missense mutation c.464G>A (p.G155D) in Ca2+-binding protein 4 (CABP4) in a Chinese pedigree with autosomal dominant nocturnal frontal lobe epilepsy.

The aim of this study was to identify disease-causing gene mutations in a Chinese family affected with autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE), a 4-generation pedigree of 27 members in the Southern Chinese Han population, including 11 individuals diagnosed with ADNFLE. DNA samples were collected from 15 family members, chinese han people, including seven affected and eight unaffected individuals. None of these patients had night blindness or visual disorders. Four affected individuals were screened for mutations using whole-exome sequencing, and 13 potentially interesting mutations shared by all the four affected individuals were validated using the Sanger sequencing method. Only one novel missense mutation c.464G>A (p.G155D) in the CABP4 gene, encoding the neuronal Ca2+-binding protein 4 (CaBP4), was present in all seven affected individuals in this family as revealed by PCR with blood DNA samples using CABP4 primers. The mutation was also found in one young unaffected family member, but was absent from 300 unrelated control subjects. The p.G155D mutation, located near the Ca2+ binding motif EF-hand 1 and the L-type Ca2+ channel (Cav1.4) binding motif within the N-terminal lobe of CaBP4, is predicted to affect protein function according to the bioinformatics tools PolyPhen-2 and SIFT. These findings suggest that mutations in the CABP4 gene may be linked to ADNFLE.

Interactions of TRAF6 and NLRX1 gene polymorphisms with environmental factors on the susceptibility of type 2 diabetes mellitus vascular complications in a southern Han Chinese population

AimsTo evaluate the effects of TRAF6 and NLRX1 polymorphisms and their interactions with environmental factors on the susceptibility of type 2 diabetes mellitus (T2DM) vascular complications in a southern Han Chinese population. MethodsFive single nucleotide polymorphisms (SNPs) were genotyped in a case-control study to estimate risk factors of T2DM vascular complications. Gene-gene and gene-environment interactions and haplotype associations were also estimated. ResultsThe CA genotype of the NLRX1 rs4245191 was identified as a risk factor for T2DM macrovascular complications and diabetic cerebral infarction (OR=2.88, 95% CI=1.15–7.22, P=0.024; OR=4.00, 95% CI=1.04–15.38, P=0.043, respectively). A significantly lower T allele frequency in the TRAF6 rs16928973 was observed in T2DM patients with both microvascular and macrovascular complications compared with patients without any complication under the allelic model (T vs. C: OR=0.36, 95% CI=0.14–0.98, P=0.038). No significant differences in haplotypes, gene-gene interactions and gene-environment interactions were observed among T2DM vascular subgroup patients. ConclusionsOur study provides evidence that the NLRX1 rs4245191 polymorphisms influence the risk of T2DM macrovascular complications and diabetic cerebral infarction.

HLA-A*24:02 as a common risk factor for antiepileptic drug-induced cutaneous adverse reactions.

Objective:To investigate the involvement of human leukocyte antigen (HLA) loci in aromatic antiepileptic drug–induced cutaneous adverse reactions.Methods:A case-control study was performed to detect HLA loci involved in aromatic antiepileptic drug–induced Stevens-Johnson syndrome in a southern Han Chinese population. Between January 1, 2006, and December 31, 2015, 91 cases of Stevens-Johnson syndrome induced by aromatic antiepileptic drugs and 322 matched drug-tolerant controls were enrolled from 8 centers. Important genotypes were replicated in cases with maculopapular eruption and in the meta-analyses of data from other populations. Sequence-based typing determined the HLA-A, HLA-B, HLA-C, and HLA-DRB1 genotypes.Results:HLA-B*15:02 was confirmed as strongly associated with carbamazepine-induced Stevens-Johnson syndrome (p = 5.63 × 10−15). In addition, HLA-A*24:02 was associated significantly with Stevens-Johnson syndrome induced by the aromatic antiepileptic drugs as a group (p = 1.02 × 10−5) and by individual drugs (carbamazepine p = 0.015, lamotrigine p = 0.005, phenytoin p = 0.027). Logistic regression analysis revealed a multiplicative interaction between HLA-B*15:02 and HLA-A*24:02. Positivity for HLA-A*24:02 and/or HLA-B*15:02 showed a sensitivity of 72.5% and a specificity of 69.0%. The presence of HLA-A*24:02 in cases with maculopapular exanthema was also significantly higher than in controls (p = 0.023). Meta-analysis of data from Japan, Korea, Malaysia, Mexico, Norway, and China revealed a similar association.Conclusions:HLA-A*24:02 is a common genetic risk factor for cutaneous adverse reactions induced by aromatic antiepileptic drugs in the southern Han Chinese and possibly other ethnic populations. Pretreatment screening is recommended for people in southern China.

Allelic diversity of KIR2DL4 gene and identification of five novel alleles among southern Han Chinese population

To study the polymorphisms of the KIR2DL4 gene in a southern Han Chinese population. Genomic DNA isolated from 306 unrelated individuals was amplified by using KIR2DL4-specific PCR primers. The PCR products were genotyped for the entire coding sequence by sequencing-based typing (SBT). Assignment of allelic profile was accomplished with an Assign 3.5 software. For samples with inconclusive SBT results, the RT-PCR products covering the entire coding sequence of the KIR2DL4 gene were subjected to cloning and haplotype sequencing. Among the 306 individuals, 11 alleles were detected, of which 5 novel alleles were officially named by the KIR subcommittee of the World Health Organization Nomenclature Committee for factors of HLA system. The observed frequencies for the 11 alleles were KIR2DL4 *00102 (75.5%), *00103 (8.2%), *00501 (34.0%), *00503 (0.7%), *00504 (0.7%), *00602 (14.4%), *00801 (11.4%), *011 (22.2%), *032 (0.3%), *033 (0.3%) and *034 (0.3%). The ratio of 10A type alleles including 2DL4*00102, *00103, *00501, *00503, *00504, *00602, *032, *033, *034 and 9A type alleles including 2DL4*00801, *011 were 97.0% and 33.0%, respectively, with a ratio of 2.9:1. The allelic diversity of the KIR2DL4 gene in southern Han Chinese has been elucidated, which may provide valuable data for research on transplantation, reproductive immunity, KIR-associated disease and evolution.

Genetic analysis of FGF20 in Chinese patients with Parkinson's disease.

Sequence variants in fibroblast growth factor 20 (FGF20) have been reported to be associated with Parkinson's disease (PD). We genotyped the rs591323 variant in a total of 2220 Han Chinese subjects, including 1051 patients with sporadic PD and 1169 controls, to investigate the association between rs591323 and the risk of PD. In addition, we also conducted a stratified analysis according to age at onset of PD and compared the clinical characteristics of AA+AG subjects with GG subjects. In this study, we confirmed that the A allele of rs591323 in FGF20 reduces the risk of developing sporadic PD (P=0.013). Additionally, subjects with the AA+AG genotype have a reduced risk compared to individuals with the GG genotype (P=0.024). This association was significant among females (P=0.036), but was not significant among males (P=0.266). Furthermore, no significant association was observed among either the early-onset PD group (P=0.051) or the late-onset PD group (P=0.187). Moreover, we demonstrated that the AA+AG subjects could not be distinguished from the GG subjects based on their clinical features. Our study is the first to demonstrate that FGF20 (rs591323) is associated with a lower risk of PD in a Southern Han Chinese population from mainland China.

The novel KIR2DL1*00602 allele identified in an individual from a southern Chinese Han population.

KIR2DL1*00602 differs from KIR2DL1*00302 by a non-synonymous mutation in exon 7.

Matrix metalloproteinase-1 promoter -1607bp 1G/2G polymorphism associated with increased risk of spinal tuberculosis in Southern Chinese Han population.

Spinal tuberculosis is the most common form of musculoskeletal tuberculosis. The expression of matrix metalloproteinase-1 (MMP-1) is increased in cells with Mycobacterium tuberculosis infection. MMP-1 plays a curial role in extracellular matrix degradation during the progression of tuberculosis. Although the 1G/2G polymorphism in MMP-1-1607 influences its transcription, its role in spinal tuberculosis remains unknown. Healthy controls and patients with spinal tuberculosis of Han ethnicity were recruited between January 2010 and May 2016. The MMP-1-1607 1G/2G polymorphism was genotyped using the Sequenom mass Array polymorphism analysis system. The genotypes of 1G/1G, 1G/2G, and 2G/2G were found in 13.7%, 53.6%, and 32.8% of patients, and 12.2%, 37.4%, and 50.4% of controls, respectively. The 1G/2G genotype were more common in cases than in controls (P=2.05E-04). The 1G allele showed an association with an increased risk for spinal tuberculosis when compared to 2G allele (P=.004). 1G genotypes, having at least one 1G allele, were associated with the risk of developing spinal tuberculosis (1G/1G+1G/2G vs 2G/2G: OR=2.084, 95%CI=1.401-3.100, P=2.65E-04). 1G genotypes of the MMP-1-1607 may be associated with susceptibility to spinal tuberculosis in Southern Chinese Han population.

ZNF208 polymorphisms associated with ischemic stroke in a southern Chinese Han population.

Ischemic stroke is one of the most common diseases with a high burden of neurological deficits, disability and death. Zinc finger protein 208 (ZNF208) was found to be involved in coronary heart disease, although little information is available about its association with ischemic stroke. We performed the present case-control study to clarify the association between single-nucleotide polymorphisms (SNPs) within ZNF208 and the risk of ischemic stroke in a southern Chinese Han population. A total of 799 subjects (400 cases and 399 healthy controls) were enrolled in the present study. Five SNPs within ZNF208 gene were selected and genotyped using Sequenom MassARRY technology (Sequenom, Inc., San Diego, CA, USA). Data management and statistical analyses were conducted using Sequenom Typer, version 4.0, and a chi-squared test, as well as unconditional logistic regression. Statistical results showed that three variants were associated with the risk of ischemic stroke under allele models (rs2188971, rs2188972, rs8103163 and rs7248488). The variant rs2188972 was also associated with the risk of ischemic stroke in a recessive model after adjustment for age and sex. Haplotype analysis suggested that a significant difference existed between the Ars2188972 Trs2188971 Ars8103163 Ars7248488 haplotype and the risk of ischemic stroke, although this disappeared after adjustment for sex and age. The results obtained in the present study indicate a potential association between ZNF208 variants and the risk of ischemic risk in a southern Chinese Han population.

Lack of association between CARD10/CARMA3 tag SNPs and psoriasis vulgaris in the southern Chinese population.

Previously, we determined that the CARD11 rs4722404 single nucleotide polymorphism (SNP) increases risk of early-onset psoriasis vulgaris (PsV). Moreover, the CARD14 gene polymorphism c.C2458T (p.Arg820Trp) is associated with clinical features of this disease. CARMA1/CARD11, CARMA2/CARD14, and CARMA3/CARD10 are conserved across many species and constitute a family of proteins, all of the members of which contain various functional domains characteristic of this group. The NF-κB signaling pathway, regulated by the CARMA family of scaffold proteins and its eponymous component, is a crucial mediator in the pathogenesis of psoriasis. However, little is known about the association between CARMA3/CARD10 and PsV. The aim of this study was to evaluate the relationship between the gene encoding this protein and risk of PsV in the southern Han Chinese population. Genomic DNA from 568 individuals of southern Chinese origin, including 355 patients with PsV and 213 control subjects, was analyzed. We selected seven tag SNPs in the CARMA3/CARD10 gene and genotyped them by the SNaPshot assay. Our results identified no significant association between these SNPs and PsV in the Chinese population examined. Future studies should focus on the potential function of the CARMA3/CARD10 gene in the pathogenesis of PsV.

A Reduced Interval of Chromosome 9p21 Locus is Associated with Ischemic Stroke in Chinese Northern Han Population

The 9p21 locus, a strong risk locus for coronary arterial disease, has been also associated with other cardiovascular disease including ischemic stroke (IS) in Caucasians. However, the association between 9p21 locus and IS in Chinese Han population is still debatable because of ambiguous results reported previously. Genetic heterogeneity between Southern and Northern Chinese Han populations could be one of the reasons for this uncertainty. Four genetic variants selected from the three conjunctional LD blocks within the 44 kb candidate region on chromosome 9p21 were genotyped in 1,429 IS patients and 1,191 healthy controls from the Northern Chinese Han population. Among the four studied variants, the G allele of the SNP rs2383207 was significantly associated with IS with allele frequency 66.8% in patients and 63.4% in controls. This association appears to be dominant with an OR of 1.417 (p=0.003) for people with either GG or AG genotypes. We did not find any association for the other three SNPs (rs1333049, rs10757274, and rs10116277). Based our results, we conclude that the 9p21 locus is a susceptibility locus for IS in the Northern Chinese Han population; and the core risk region for IS is within an interval of less than 28kb.

Validation of the multiplex ligation‐dependent probe amplification assay and its application on the distribution study of the major alleles of 17 blood group systems in Chinese donors from Guangzhou

Genotyping platforms for common red blood cell (RBC) antigens have been successfully applied in Caucasian and black populations but not in Chinese populations. In this study, a genotyping assay based on multiplex ligation-dependent probe amplification (MLPA) technology was applied in a Chinese population to validate the MLPA probes. Subsequently, the comprehensive distribution of 17 blood group systems also was obtained. DNA samples from 200 Chinese donors were extracted and genotyped using the blood-MLPA assay. To confirm the MLPA results, a second independent genotyping assay (ID Core+) was conducted in 40 donors, and serological typing of 14 blood-group antigens was performed in 91 donors. In donors who had abnormal copy numbers of an allele (DI and GYPB) determined by MLPA, additional experiments were performed (polymerase chain reaction, sequencing, and flow cytometry analysis). The genotyping results obtained using the blood-MLPA and ID Core+ assays were consistent. Serological data were consistent with the genotyping results except for one donor who had a Lu(a-b-) phenotype. Of the 17 blood group systems, the distribution of the MNS, Duffy, Kidd, Diego, Yt, and Dombrock systems was polymorphic. The Mur and Sta antigens of the MNS system were distributed with a frequency of 9% (18 of 200) and 2% (4 of 200), respectively. One donor with chimerism and one who carried a novel DI*02(A845V) allele, which predicts the depression of Dib antigen expression, were identified. The blood-MLPA assay could easily identify the common blood-group alleles and correctly predicted phenotype in the Chinese population. The Mur and Sta antigens were distributed with high frequency in a Southern Chinese Han population.

MICA Gene Deletion in 3411 DNA Samples from Five Distinct Populations in Mainland China and Lack of Association with Nasopharyngeal Carcinoma (NPC) in a Southern Chinese Han population.

Deletion of major histocompatibility complex class I chain-related genes A (MICA*Del) was investigated in 3,411 DNA samples from two southern Chinese Han populations (Hunan Han, HNH; Guangdong Han, GDH), two northern Chinese populations (Inner Mongolia Han, IMH; Inner Mongolia Mongol, IMM) and one southeastern Chinese Han population (Fujian Han, FJH) using an in-house polymerase chain reaction-sequence specific priming (PCR-SSP) assay, which enables direct discrimination between heterozygote and homozygote for MICA*Del. MICA*Del showed a frequency ranging from 0.8% in FJH to 5.7% in IMM (Pcorrected < 0.05), indicating northward increase in frequency of MICA*Del in Chinese populations. In contrast to the association reported recently in a Taiwan Chinese population and aMalaysian Chinese cohort, MICA*Del distribution did not differ between 1,120 patients with nasopharyngeal carcinoma (NPC) and 1,483 normal controls in the HNH population (1.03% in NPC cases vs 1.18% in the controls, OR (95% CI) = 0.87 (0.51-1.47), p = 0.69). Further gender-stratified analysis also failed to disclose any male-specific association reported in a Taiwan Chinese population. Multi-locus typing of the 94 samples carrying MICA*Del revealed two new haplotypes, HLA-A*11:01-B*13:01-MICA*Del-MICB*009N-DRB1*04:06 and HLA-B*35:01-MICA*Del-MICB*009N-DRB1*15:01, in addition to HLA-B*48-MICA*Del. Unexpectedly, two samples with MICA*Del in the HNH population were each consistently found to have two distinct MICA alleles, indicating the existence of two MICA gene copies on certain HLA haplotypes. Based on the results from a sizeable case-control study, our data suggest that there is no association between MICA*Del and NPC in the southern Chinese Han population.

Association of GWAS-Supported Variants rs556621 on Chromosome 6p21.1 with Large Artery Atherosclerotic Stroke in a Southern Chinese Han Population.

Recent genome-wide association study associated rs556621 on chromosome 6p21.1 with the risk of large artery atherosclerotic (LAA) stroke in Caucasians. However, subsequent replicate studies showed conflict results in different ethnicities. This study aimed to evaluate whether rs556621 was associated with LAA stroke in Chinese Han population. In this case-control study, 659 patients with LAA stroke and 650 healthy controls were enrolled. Associations between rs556621 genotypes and LAA stroke were analyzed with logistic regression model. Rs556621 variants were associated with increased risks of LAA stroke (codominant model: OR 1.42; 95% CI 1.01-1.99; P=0.010; recessive model: OR 1.40; 95% CI 1.05-1.86; P=0.003). When subjects were stratified by sex, TT genotype of SNP rs556621 was associated with an increased risk of LAA stroke in female when tested with recessive model (OR 2.36; 95% CI 1.28-4.36, P=0.006). In male subjects, however, no significant association was detected. Smoking status, sex did not significantly influence the relationship between genotypes of rs556621 and risk of LAA stroke (P interaction=0.140, P interaction=0.076). Rs556621 may play an important role in the development of LAA stroke in female Chinese of Han ethnicity. Larger studies with subjects of different ethnicities are warranted to confirm these findings.

Association of NKAPL, TSPAN18, and MPC2 gene variants with schizophrenia based on new data and a meta-analysis in Han Chinese.

Schizophrenia (SZ) is suggested to be a complex polygenetic disorder with high heritability. Genome-wide association studies have found that the rs1635, rs11038167, and rs10489202 polymorphisms are associated with SZ in Han Chinese. However, results of validation studies are inconsistent. This study aimed to test the association between the NKAPL rs1635, TSPAN18 rs11038167, and MPC2 rs10489202 polymorphisms and SZ in a Chinese population. This study contained 700 unrelated SZ patients (300 Zhuang and 400 Han) and 700 gender- and age-matched controls (300 Zhuang and 400 Han). The polymorphisms in TSPAN18 (rs11038167), NKAPL (rs1635), and MPC2 (rs10489202) were genotyped using the Sequenom MassARRAY method. Statistical analyses were performed with PLINK program and SPSS l6.0 for Windows. STATA11.1 was used for meta-analysis. No statistically significant difference was found in different allele and genotype frequencies of rs1635, rs11038167, and rs10489202 between SZ cases and controls of Zhuang and Han ethnicities and the total samples (all p>0.05). Further meta-analysis suggested that single-nucleotide polymorphism rs10489202 was significantly associated with SZ in a Han Chinese population (p OR=0.002). Our case-control study failed to validate the significant association of NKAPL rs1635, TSPAN18 rs11038167, and MPC2 rs10489202 polymorphisms with SZ susceptibility in the southern Zhuang or Han Chinese population. However, meta-analysis showed a significant association between MPC2 variant rs10489202 and SZ susceptibility in Han Chinese.

SNP in Differentially Methylated Region Upstream of H19 Gene in Guangdong Han Population.

To investigate the single nucleotide polymorphism （SNP） and haplotypes in differentially methylated region （DMR） upstream of H19 gene in Guangdong Han population. The PIA typing and restriction enzyme McrBC and HpaⅡ were used to digest the genomic DNA and obtain the individual uniparental DNA template strand. The data of uniparental SNP alleles, genotypes and haplotypes in DMR upstream of H19 gene were obtained by sequencing. A total of 13 SNPs （rs10840167, rs2525883, rs12417375, rs4930101, rs2525882, rs2735970, rs2735971, rs11042170, rs2735972, rs10732516, rs2071094, rs2107425, and rs4930098） and one mutation locus （g7351c） were found. All loci followed the Hardy-Weinberg equilibrium （P>0.05） by statistical analysis. Except for rs12417375 （DP=0.279） locus, the DP of remaining 12 SNPs were 0.446-0.614, and the g7351c mutation locus （DP=0.013） was the particular loci of the Southern Chinese Han population. Eight haplotypes （designated as haplotype 1-8） were detected, in which 3 haplotypes had not yet been reported and the DP, PIC, PE and H were 0.891, 0.714, 0.524 and 0.758, respectively. Obtained by PIA typing, the SNP in DMR upstream of H19 gene and its haplotypes genetic marker system have a high determination power and show a good practical value in forensic identification.

Identification of a new HLA-G allele, HLA-G*01:19, by cloning and phasing.

A new HLA-G allelic variant, HLA-G*01:19, was identified in a southern Chinese Han population by polymerase chain reaction-sequence-based typing (PCR-SBT), cloning and phasing. HLA-G*01:19 differs from HLA-G*01:04:01 by a nonsynonymous cytosine at position 99 in exon 2, resulting in amino acid change from valine to leucine at codon 34 of the mature HLA-G molecule.

Characterization of a novel HLA‐B*40 allele, HLA‐B*40:186:02, by cloning and sequencing

A novel HLA-B*40 variant, HLA-B*40:186:02, has been identified by cloning and sequencing in a southern Chinese Han population. Aligned with HLA-B*40:01:01, HLA-B*40:186:02 has a nonsynonymous cytosine mutation at nucleotide position 165 in exon 2, leading to amino acid change from glycine to arginine at codon 56. It differs from HLA-B*40:186:01 by a synonymous change (adenine to cytosine) at position 165 in exon 2.

Association of polymorphisms in the MyD88, IRAK4 and TRAF6 genes and susceptibility to type 2 diabetes mellitus and diabetic nephropathy in a southern Han Chinese population

Type 2 diabetes mellitus (T2DM) has been linked to a state of low-grade inflammation resulting from abnormalities in the innate immune pathway. MyD88 is an essential adaptor protein for TLR signaling, which is involved in activating NF-κB through IRAK4 and TRAF6. To investigate the effects of the MyD88, IRAK4 and TRAF6 polymorphisms in the susceptibility of T2DM and diabetic vascular complications, eight SNPs were analyzed in 553 T2DM patients and 553 matched healthy controls. Gene-gene interactions and haplotype associations were also evaluated. We found a significant increased risk of T2DM for the AG genotype of rs6853 in MyD88 gene and the CT genotype of rs4251532 in IRAK4 gene. Significant association was also found between rs16928973 in TRAF6 gene and diabetic nephropathy (DN) under the allelic model. Moreover, the TA haplotype in TRAF6 was negatively associated with DN. No significant gene-gene interactions were found. In conclusion, our results indicate that the polymorphisms in TLR-MyD88-NF-κB signaling pathway confer genetic susceptibility to T2DM and DN.