Association of STAT4 rs7574865 polymorphism with autoimmune diseases: a meta-analysis.

The association between the signal transducer and activator of transcription 4 (STAT4) gene rs7574865 single nucleotide polymorphism and different autoimmune diseases remains controversial and ambiguous. We conducted this study to investigate whether combined evidence shows the association between STAT4 rs7574865 polymorphism and autoimmune diseases. Comprehensive Medline search and review of the references were used to get the relevant reports published before September 2011. Meta-analysis was conducted for genotype T/T (recessive effect), T/T + G/T (dominant effect) and T allele in random effects models. 40 studies with 90 comparisons including 32 systemic lupus erythematosus (SLE), 19 rheumatoid arthritis (RA), 3 type 1 diabetes (T1D), 11 Systemeric Sclerosis (SSc), 4 inflammatory bowed diseases (IBD), 3 Primary Sjogren's syndrome (pSS), 4 juvenile idiopathic arthritis (JIA), 2 Primary antiphospholipid syndrome (APS), 1 Autoimmune thyroid diseases, 1 multiple sclerosis, 1 Psoriasis, 1 Wegener's granulomatosis, 1 Type 2 diabetes, and 1 giant cell arteritis disease were available for this meta-analysis. The overall odds ratios for rs7574865 T-allele significantly increased in SLE, RA, T1D, SSc, JIA, and APS (OR = 1.56, 1.25, 1.13, 1.34, 1.25, and 2.15, respectively, P < 0.00001) and in IBD-UC and pSS (OR = 1.11 and 1.33, respectively, P < 0.05). This meta-analysis demonstrates that the STAT4 rs7574865 T allele confers susceptibility to SLE, RA, T1D, SSc, JIA, APS, IBD-UC, and pSS patients, supporting the hypothesis of association between STAT4 gene polymorphism and subgroup of autoimmune diseases.

The CRISPLD2 gene is involved in cleft lip and/or cleft palate in a Chinese population.

BACKGROUND: Nonsyndromic cleft lip and/or cleft palate (NSCLP) are common congenital anomalies in humans, the etiologies of which are complex and associated with both genetic and environmental factors. Previous data suggested single nucleotide polymorphisms (SNPs) of rs1546124, rs4783099, and rs16974880 of the CRISPLD2 gene were associated with an increased risk of NSCLP; however, subsequent studies have yielded conflicting results. This study aims to evaluate the associations of the aforementioned polymorphisms with NSCLP in a Northwestern Chinese population. METHODS: Three CRISPLD2 SNPs were genotyped in a case-control study (n = 907), including 444 NSCLP patients and 463 healthy individuals, using polymerase chain reaction-denaturing high-performance liquid chromatography (PCR-DHPLC). RESULTS: The genotype and allele frequencies of rs1546124 (odds ratio [OR], 2.30; 95% confidence interval [CI], 1.58-3.34; p = 1 × 10(-5) ) and rs4783099 (OR, 0.73; 95% CI, 0.54-1.00; p = 0.05) were different in NSCLP patients compared with controls. Furthermore, the CC genotype at rs1546124 was associated with increased risk for cleft lip with or without cleft palate (CL/P; OR, 2.11; 95% CI, 1.41-3.15; p(correct) = 1.5 × 10(-4) ) and for cleft palate only (CPO; OR, 2.93; 95% CI, 1.69-5.07; p(correct) = 5.4 × 10(-4) ), whereas the T allele of rs4783099 was associated with decreased risk for CPO. Further gender stratification showed that the statistical association of these two loci is mainly in the male patients, and not in female patients. CONCLUSION: Our results suggest that the CRISPLD2 gene contributes to the etiology of NSCLP in the Northwestern Chinese population. SNP rs1546124 is significantly related to NSCLP, associated with both CL/P and CPO groups, and SNP rs4783099 is significantly associated with CPO.

Signal transducer and activator of transcription 4 gene polymorphisms associated with rheumatoid arthritis in Northwestern Chinese Han population.

AIMS: Signal transducer and activator of transcription 4 (STAT4) gene encode a transcriptional factor that transmits signals induced by several key cytokines which play important roles in the development of autoimmune diseases. Recently, several single nucleotide polymorphisms (SNPs) in STAT4 gene have been reported to be significantly associated with Rheumatoid arthritis (RA) in different ethnic populations. We undertook this study to investigate whether the association of STAT4 genetic polymorphisms with RA is present in Northwestern Chinese Han population. MAIN METHODS: A case-control association study in individuals with RA (n=208) and healthy controls (n=312) was conducted. Four SNPs (rs7574865, rs8179673, rs10181656, rs11889341) in STAT4 gene were genotyped by using polymerase chain reaction followed by denaturing high-performance liquid chromatography (PCR-DHPLC) and DNA sequencing. KEY FINDINGS: The genotype and allele distributions of four polymorphisms were significantly different in individuals with RA compared to controls, with SNP rs7574865 T allele and T/T genotype showing the most significant association with susceptibility to RA (uncorrected P=1×10(-4), OR=1.645, 95% CI=1.272-2.129; uncorrected P=4.8×10(-5), OR=3.111, 95% CI=1.777-5.447, respectively). Stratification studies showed that STAT4 gene polymorphisms were significantly associated with anti-cyclic citrullinated peptide (anti-CCP) positive subgroup in Northwestern Chinese Han population. SIGNIFICANCE: These findings strongly suggest that STAT4 genetic polymorphisms are associated with RA in Northwestern Chinese Han population, and support the hypothesis of STAT4 gene polymorphisms increasing the risk for RA across major populations.

Fc receptor-like 3 gene polymorphisms confer susceptibility to rheumatoid arthritis in a Chinese population.

Polymorphisms in the Fc receptor-like 3 (FCRL3) gene have been reported to be associated with rheumatoid arthritis (RA) in Japanese populations. However subsequent studies have yielded conflicting results. Hence the aim of present study was to clarify whether these genetic variants in FCRL3 gene are associated with RA in a Chinese population. We conducted a case-control study of 234 RA patients and 260 controls by genotyping four polymorphisms in FCRL3. The genotype and allele distributions of four polymorphisms were significantly different in RA patients compared with controls (uncorrected p = 0.021 and p = 0.031; 0.027 and 0.008; 0.028 and 0.042; and 0.019 and 0.029, respectively). The FCRL3-169 C allele was significantly associated with rheumatoid factor (RF) and anti-cyclic citrullinated peptide (anti-CCP)-positive RA, but no association was detected for RF and anti-CCP-negative RA. Furthermore, the frequency of the -169C allele was increased disproportionately in female patients, and the resulting odds ratio for female homozygote was increased to 2.375 (uncorrected p = 0.006). Haplotype analysis showed that the most common haplotype TGGG was associated with decreased risk of RA (uncorrected p = 0.001, odds ratio = 0.656). However CACA appeared to be a risk haplotype for RA cases (uncorrected p = 0.031, odds ratio = 1.398). Taken together, these results suggest that FCRL3 polymorphisms and haplotypes may contribute to genetic susceptibility to RA in Chinese population.