Distribution of an NcoI polymorphism in the lymphotoxin alpha gene in Dutch patients with inflamatory bowel diseases.

An NcoI restriction fragment length polymorphism in the first intron of the lymphotoxin alpha gene was investigated in 35 patients with Crohn's disease, 40 patients with ulcerative colitis, and 30 unrelated healthy controls, all of Dutch origin. The results showed that no significant differences existed in the genotype frequencies of the NcoI polymorphism in the first intron of the LT alpha gene between ulcerative colitis patients or Crohn's disease patients and the healthy controls. The study indicates that the NcoI polymorphism in the LT alpha gene can not be used as a genetic marker for the predisposition to inflammatory bowel diseases. However, since this polymorphism may control the production of tumor necrosis factor, study of this and other related tumor necrosis factor gene polymorphisms may be used as markers to identify patient subgroups and to define patient heterogeneity. Further studies are being carried out on other polymorphisms and on the relevance of LT alpha and TNF alpha haplotypes.

     

NO ASSOCIATION BETWEEN TUMOR NECROSIS FACTOR ALPHA AND OBSESSIVE COMPULSIVE DISORDER IN CHINESE HAN POPULATION

Objective To investigate association between tumor necrosis factor alpha (TNF-α) and obsessive compulsive disorder (OCD) in Chinese Han population.Methods Plasma concentrations of TNF-α were measured in 61 drug-free patients who fulfilled DSM-Ⅳ criteria for OCD and 93 healthy controls.TNF-α concentrations in blood were determined by enzyme-linked immunosorbent assay (ELISA).Two polymorphisms of TNF-α gene were investigated in the same patients and healthy controls:-308 G/A and-238 G/A.The allelic and genoty...     

ANALYSIS OF INTERLEUKIN-1 RECEPTOR ANTAGONIST GENE POLYMORPHISM IN CHINESE PATIENTS WITH ALZHEIMER＇S DISEASE

Objective To identify an interaction between the interleukin-1 receptor antagonist gene polymorphism and risk of AIzheimer‘s disease. Methods The study included 117 healthy controls, 85 patients with Alzheimer‘s disease in a Northeastern Chinese population of Han nationality. Genotypes were determined by a polymerase chain reaction amplification of the intron 2 fragment ,harbouring a variable number of short tandem nucleotide sequences. Amplification products were separated on a 2% agarose gel. Results The allele 2 frequency was 27% in healthy controls, and 21% in patients with Alzheimer‘s disease. Thus for allele 2 as well as for all other alleles, genotypes, or carriage rates, no significant differences compared with controls. Conclusions No association of interleukin-1 receptor antagonist gene polymorphism with Alzheimer‘s disease was identified in this population. It is also possible that the increased risk and disease modifying effects are caused by linkage disequilibrium with other genomic variants in other nearby genes.     

Genetic susceptibility to ulcerative colitis in the Chinese Han ethnic population: association with TNF polymorphisms

Background Tumor necrosis factor α （TNFα） is an important proinflammatory cytokine that has been implicated in the pathogenesis of inflammatory bowel disease （IBD）. Recent studies have evaluated the role of TNF promoter polymorphisms in IBD, whereas the data are inconsistent. Trans-racial mapping in an ethnically distinct but homogenous population may help clarify these associations. We investigate the association between TNF promoter polymorphisms and susceptibility to ulcerative colitis （UC） in the Chinese Han ethnic population. Methods We studied 110 unrelated UC patients and 292 healthy controls from Zhejiang Province, China. Genotyping for 6 common TNF promoter polymorphisms （TNF -1031T/C, -863C/A, -857C/T, -380G/A, -308G/A, -238G/A） was carried out by polymerase chain reaction sequence-specific primers （PCR-SSP）. Results TNF-308A was associated with disease （allele frequency patients 14.6% vs controls 8.9%, P=0.02）. TNF -857T was increased in patients but without statistical significance （allele frequency 17.3% vs 12.2%, P=0.06）. Haplotype analysis revealed 6 haplotypes including two （H5 and H3）, which contained TNF -308A. H5 was associated with disease （haplotype frequency patients -12.3% vs controls 7.5%, P=0.03）. Of note the rare haplotype H3 has not previously been identified in Caucasian populations. Homozygosity for the haplotype H4 comprising the common alleles at each TNF promoter single-nucleotide polymorphism （SNP） was negatively associated with disease （patients vs controls 24.5% vs 34.9%, P〈0.05）. Conclusions We report the association with TNF -308A polymorphisms in Chinese patients with ulcerative colitis. The functional study in Chinese Han ethnic population is now required.     

Atrial natriuretic peptide gene polymorphism is not associated with hypertrophic cardiomyopathy

Background Hypertrophic cardiomyopathy （HCM） is a primary autosomal dominant inheritant myocardial disease with heterogeneity in clinical manifestations, natural history and prognosis. Even carrying an identical gene mutation among family members, a va[iety of clinical phenotypes have been found in patients with HCM. Modifier genes may contribute to the diversity. The plasma levels of atrial natriuretic peptides （ANP） were found previously to be elevated in HCM. Our studies suggested that ANP gene promoter polymorphism is associated with left ventricular hypertrophy in hypertension. The present study aimed to determine whether the two SNPs in the ANP gene are associated with HCM Methods We determined the relationships between the ANP gene polymorphism and HCM in 262 HCM patients and 614 age- and sex-matched healthy individuals. All of the subjects were genotyped for -A2843G and A188G polymorphisms. Results The genotype frequency in the -A2843G and A188G polymorphisms of the ANP gene was not significantly different between the HCM patients and controls. The -A2843G and A188G polymorphisms were also not associated with clinical phenotype in cardiomyopathy patients. Conclusions The polymorphisms of the ANP gene are not associated with increasing risk of HCM or clinical phenotypes. The variations of the ANP gene may not serve as a genetic modifier for the development of HCM.     

TNFR 2 M196R polymorphism and acne vulgaris in Han Chinese: A case-control study

In this case-control study,the relationship between M196R(676 T→G) variant in exon 6 of tumor necrosis factor receptor type 2(TNFR2) gene and genetic susceptibility of acne vulgaris in Han Chinese was investigated.A total of 93 acne vulgaris patients and 90 healthy subjects from Han Chinese ethnic group were enrolled in this study.Polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP) technique was adopted to analyze the single nucleotide polymorphisms(SNPs) of TNFR2 M196R gene,and to ...     

Association of gene polymorphisms of tumour necrosis factor-α and interleukin-13 with chronic obstructive pulmonary disease in Han nationality in Beijing

Background Genetic factors are believed to play a role in the individual susceptibility to chronic obstructive pulmonary disease (COPD). A single nucleotide polymorphism (SNP) of tumour necrosis factor-α (TNF-α)has been reported but inconsistent results may arise from different populations and phenotypes of COPD. There are only a few published studies of interleukin-13 (IL-13) SNPs on COPD. The SNPs of TNF-α and IL-13 have not been studied in the Chinese population. This research was conducted to study the frequencies of IL-13 gene promoter 1055 (IL-13-1055) and TNF-α gene-308 polymorphisms in the patients with COPD and to investigate the effect of those genetic polymorphisms on COPD in the Chinese population.Methods A cohort of COPD patients and age matched controls were recruited from an inpatient hospital service in Beijing. Venous blood was obtained and genomic DNA was extracted from peripheral blood monocytes using standard method. Genomic DNA was used as a template for amplification by polymerase chain reaction(PCR) to determine the polymorphism at -1055 in the length polymorphism (RFLP) was used to determine polymorphisms in the TNF-α gene-308 position. The products were investigated by sequence analysis also.Results One hundred and eleven COPD patients and 97 controls were studied. Seventy-five cases were current smokers in COPD patients and 36 were current smokers in controls. The frequencies of TT genotype in the IL-13 gene promoter region were 11.7% ( 13/111 ) in the COPD group and 13.4% (13/97) in the controls (P =0. 713). However, the OR value of TT genotype was significantly increased to 6.4 (95% CI 1.62 -25.39) in the smokers with COPD. TT genotype was also positively related to family history of COPD, OR =7. 7 (95% CI 1.37 -43.80). The frequencies of A allele in the TNF-α gene were 5.9% in COPD and 3. 1% in controls (P=0. 131 ). The OR value of A allele was 5.0 (95% CI 1.011 to 25. 059) in smokers with COPD.Conclusions There is no significant difference in the frequencies of the TT genotype of IL-13-1055 or the A allele of the TNF-α between Han Chinese patients with COPD versus control. Thus, it does not appear that these SNPs are independent factors in COPD for Han nationality in Beijing. However, these SNPs may increase the risk of COPD among smokers.     

Association of the apolipoprotein B gene polymorphisms with essential hypertension in Northern Chinese Han population

Objective To study the association of the apolipoprotein B gene polymorphisms with essential hypertension in Northern Chinese Han population. Methods XbaI and EcoRI polymorphisms of the apolipoprotein B (APOB) gene were genotyped by polymerase chain reaction (PCR) and restriction fragment-length polymorphism (RFLP) method in 503 unrelated hypertensive patients and 490 healthy controls recruited from international collaborative study of cardiovascular disease in Asia (InterAsia). Results The difference in the genotypic distributions could be neglected across the groups. The prevalence of X allele in healthy controls (4.8%) was less frequent in Chinese, and there was no significant difference in the frequency of the X allele between cases (5.7%) and controls (P=0.38). The observed E- allele frequencies were closely similar among groups (5.9% in cases vs 5.0% in controls, P=0.39). Logitstic regression analyses revealed that the lack of association still persisted after adjustment of other environmental factors. Haplotype analysis showed that X-E was most frequent and no haplotype could significantly contribute to essential hypertension. Conclusion The APOB gene XbaI and EcoRI polymorphisms are not associated with essential hypertension in the Northern Chinese Han population. Future studies on single nucleotide polymorphisms in larger samples are needed to further investigate the possible contribution of the APOB gene to essential hypertension.     

TUMOR NECROSIS FACTOR-ALPHA POLYMORPHISM AND SECRETION IN MYASTHENIA GRAVIS

Objective To analyze the relationship between tumor necrosis factor-alpha (TNFo) gene promoter -308 polymorphism and myasthenia gravis (MG) in Chinese and analyze secretion of TNFo in peripheral blood mononuclear cells (PBMC) in MG patients.Methods A biallelic polymorphism at position -308 in the promoter of TNFα gene was screened by PCR amplification and NcoI recognition site. One hundred and twenty-three MG cases and 115 healthy controls were included in this study. MG patients were classified to different groups according to clinical type, age at onset, and sex respectively. PBMC were isolated from 20 patients and 20 healthy controls, and then cultured in the presence or absence of phytohemagglutinin (PHA) and acetycholine receptors (AchR). The supernatants were harvested after incubation and stored until TNFαwas assayed by enzyme-linked immunosorbent assay.Results The frequency of TNFα-308 allele 2 (A) was found significantly increase in MG patients and showed a trend especially in late onset (≥ 40 years) and male patients (P ＜ 0.05). The allele A had no relationship with thymic pathogenesis in MG patients. But frequency of allele A was significantly higher in general type than in ocular type (P ＜ 0.05). MG patients had a higher inducible level of TNFα by PHA and AchR, and could be down regulated after treatment.Conclusion Polymorphism in TNFα gene promoter -308 is associated with onset of MG. The microsatellite allele TNFα2 confer risk for the development of MG in Chinese patients. MG patients have a higher inducible level of TNFα.     

Association between peroxisome proliferator-activated receptor-γ coactivator-1α gene polymorphisms and type 2 diabetes in southern Chinese population: role of altered interaction with myocyte enhancer factor 2C

Background Some single nucleotide polymorphisms (SNPs) in the peroxisome proliferator-activated receptor-γ coactivator (PGC)-1α gene have been reported to be associated with type 2 diabetes in different populations, and studies on Chinese patients yielded controversial results. The objective of this case-control study was to explore the relationship between SNPs of PGC-1α and type 2 diabetes in the southern Chinese population and to determine whether the common variants: Gly482Ser and Thr394Thr, in the PGC-1α gene have any impacts on interaction with myocyte enhancer factor (MEF) 2C.Methods The SNPs in all exons of the PGC-1α gene was investigated in 50 type 2 diabetic patients using polymerase chain reaction-single strand conformational polymorphism (PCR-SSCP) and direct sequencing. Thereafter, 263 type 2 diabetic patients and 282 healthy controls were genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). A bacterial two-hybrid system and site-directed mutagenesis were used to investigate whether Gly482Ser and Thr394Thr variants in the PGC-1α gene alter the interaction with MEF2C.Results Three frequent SNPs (Thr394Thr, Gly482Ser and Thr528Thr) were found in exons of the PGC-1α gene. Only the Gly482Ser variant had a different distribution between diabetic patients and healthy subjects, with the 482Ser allele more frequent in patients than in controls (40.1% vs 29.3%, P<0.01). Even in controls, the 482Ser(A) carriers were more likely to have higher levels of total cholesterol and low-density lipoprotein cholesterol than the 482Gly(G) carriers. The 394A-482G-528A haplotype was associated with protection from diabetes, while the 394A-482A-528A was associated with the susceptibility to diabetes. The bacterial two-hybrid system and site-directed mutagenesis revealed that the 482Ser variant was less efficient than the 482Gly variant to interact with MEF2C, whereas the 394Thr (A) had a synergic effect on the interaction between 482Ser variant and MEF2C.Conclusions The results suggested that the 482Ser variant of PGC-1α conferred the susceptibility to type 2 diabetes in the southern Chinese population. The underlying mechanism may be attributable, at least in part, to the altered interaction between the different variants (Gly482Ser, Thr394Thr) in the PGC-1α gene and MEF2C.     

Association between DPP6 polymorphism and the risk of sporadic amyotrophic lateral sclerosis in Chinese patients

Background Amyotrophic lateral sclerosis （ALS） is a progressive degenerative disease characterized by the loss of motor neurons in the spinal cord, brainstem, and cerebral cortex, which results in muscle weakness, atrophy. Sporadic ALS （SALS） accounts for about 90% of ALS cases, but the etiology is largely unknown. Most of the researchers consider it to be a complex disease. There have been several genome-wide association （GWA） studies reporting several single nucleotide polymorphisms （SNPs） which are susceptible to ALS, but no data of Asians （including Chinese） yet. We investigate whether the polymorphism of rs10260404 in DPP6 gene is associated with SALS in Chinese Han origin to compare the ethnic differences between Chinese Han origin and other populations. Methods The genomic DNA was extracted from the leukocytes of whole blood samples in 58 Chinese Han patients with SALS and 52 healthy controls. The asymmetric PCR was processed in the presence of an unlabeled probe that contained the rs10260404 locus. The product was genotyped on a light scanner using high resolution melting method and some were confirmed with sequencing. Results The rs10260404 polymorphism was in Hardy-Weinberg equilibrium in patients and controls. The CC genotype and the C allele were similar in patients compared with healthy subjects and not associated with an increased risk of Chinese SALS patients （X^2=0.29, OR=1.26, 95% CI 0.55-2.87, P 〉0.05）. Conclusions The rs10260404 is not associated with ALS susceptibility in Chinese people with Han origin which may be due to ethnic differences. More study with large number of cases in Chinese population is really necessary.     

Apolipoprotein E genotype in patients with Alzheimer’s disease

Objective To explore the frequency and significance of ApoE gene polymorphisms in patients with sporadic Alzheimer’s disease (AD).Methods Single nucleotide polymorphisms of the ApoE gene were analyzed in 32 cases of AD and 26 controls, using PCR and gene sequencing.Results The single nucleotide polymorphism of ApoE gene 462C/G was significantly associated with AD (P<0.05).Conclusions The 462C/G polymorphism might be a specific genotype in Chinese patients with sporadic AD.     

Endothelial Nitric Oxide Synthase Gene Polymorphisms Associated with Susceptibility to High Altitude Pulmonary Edema in Chinese Railway Construction Workers at Qinghai-Tibet over 4500 Meters above Sea Level

Objective To examine whether the polymorphisms of endothelial nitric oxide synthase （eNOS） gene are associated with the susceptibility to high altitude pulmonary edema （HAPE） in Chinese railway construction workers at Qinghai-Tibet where the altitude is over 4 500 m above sea level. Methods A case-control study was conducted including 149 HAPE patients in the construction workers and 160 healthy controls randomly recruited from their co-workers, matching the patients in ethnicity, age, sex, lifestyle, and working conditions. Three polymorphisms of eNOS gene, T-786C in promoter, 894G/T in exon 7, and 27bp variable number tandem repeat （VNTR） in intron 4, were genotyped using polymerase chain reaction （PCR） and confirmed with DNA sequencing. Results The frequencies of 894T allele and heterozygous G/T of the 894G/T variant were significantly higher in HAPE patients group than in the control group （P=0.0028 and P=0.0047, respectively）. However, the frequencies of the T-786C in promoter and the 27bp VNTR in intron 4 were not significantly different between the two groups. Haplotypic analysis revealed that the frequencies of two haplotypes （H3,T-T-b, b indicates 5 repeats of 27 bp VNTR; H6, C-G-a, a indicates 4 repeats of 27 bp VNTR） were significantly higher in HAPE patients （both P〈0.0001）. On the contrary, the frequencies of H1 （T-G-b） and H2 （T-G-a） were lower in HAPE patients than in healthy controls （both P〈0.001）. Conclusions Two haplotypes （T-T-b and C-G-a） may be strongly associated with susceptibility to HAPE. Compared with the individual alleles of eNOS gene, the interaction of multiple genetic markers within a haplotype may be a major determinant for the susceptibility to HAPE.     

IL-10 polymorphism is associated with increased incidence of severe sepsis

Objective To investigate whether three biallelic polymorphisms at positions -592, -819 and -1082 in the promoter region of the IL-10 gene are associated with increased incidence of severe sepsis.Methods The IL-10 -592, -819 and -1082 polymorphisms were typed using polymerase chain reaction followed by digestion with the restriction enzymes RsaⅠ, MaeⅢ and MnlⅠ, respectively. Results Patients with severe sepsis were more likely to have IL-10 -1082 allele 1, compared with controls (P<0.05). Genotype distribution of the IL-10 -1082 polymorphism significantly differed between patients and controls (P<0.05). However, the allele frequencies and genotype distribution of the IL-10 -1082 polymorphism did not differ between surviving and dead patients (P>0.05). No significant differences in the genotype distribution and allele frequencies of the IL-10 -592 and IL-10 -819 polymorphisms were observed between patients with severe sepsis and heathy controls, nor between surviving and dead patients (P> 0.05). Conclusions The polymorphism at position -1082 in the promoter region of the IL-10 gene may be associated with susceptibility to severe sepsis. In constrast, the other two highly linked IL-10 polymorphisms are not associated with incidence or the outcome of severe sepsis.     

Genetic polymorphisms of the renin-angiotensin-aldosterone system in Chinese patients with end-stage renal disease secondary to IgA nephropathy

Background Genetic variability in the renin-angiotensin-aldosterone system may modify renal responses to injury and disease progression. The angiotensin I-converting enzyme （ACE） gene insertion/deletion （I/D）, the angiotensinogen （AGT） gene, M235T, the aldosterone synthase （CYP11B2） gene, C-344T, and the angiotensin II type 1 receptor （AT1R） gene, Al166C, have been shown to be associated with IgA nephropathy （IgAN） and its progression. We determined the presence of these polymorphisms in 130 Chinese patients with IgAN, including 47 patients with end-stage renal disease （ESRD） and 120 healthy Chinese subjects, to assess their impact on the susceptibility to disease and the liability of progression to ESRD. Methods Genotyping was performed with DNA isolated from peripheral leucocytes using polymerase chain reaction amplification of the polymorphic sequence, restriction enzyme digestion, and separation and identification of DNA fragments. Clinical data from renal biopsies were collected. Results ACE, AGT, CYP and AT1R genotype distributions were similar in patients with IgAN and in controls. Comparing patients with ESRD （IgAN-ESRD） and those without ESRD （IgAN-non ESRD）, there was a significant increase only in the ACE DD genotype （P 〈0.05） among the four gene polymorphisms. There was significant dominance of the male （P 〈0.05）, more marked hypertension （P 〈0.01）, proteinuria （P 〈0.01） and increased serum creatinine during renal biopsy （P〈0.01） in the IgAN-ESRD group. Conclusion Among the ACE, AGT, ATIR and CYP gene polymorphisms, only the DD genotype may predispose the individual to increased risk of progression to ESRD in the Chinese population.     

Relationship between polymorphisms of genes encoding microsomal epoxide hydrolase and glutathione S-transferase P1 and chronic obstructive pulmonary disease

Background Cigarette smoking is the major risk factor for chronic obstructive pulmonary disease (COPD). However, only 10% -20% of chronic heavy cigarette smokers develop symptomatic disease. COPD is most likely the result of complex interactions between environmental and genetic factors. Genetic susceptibility to COPD might depend on the variations in enzyme activities that detoxify cigarette smoke products, such as microsomal epoxide hydrolase (mEH) and glutathione Stransferase (GST). In this study, we investigated the relationship between polymorphisms in the genes encoding mEH and glutathione S-transferase P1 (GSTP1) and COPD in a Chinese population.Methods Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was performed to find mEH polymorphism in exon 3 (Tyr113→His), exon 4 (His139→Arg) and GSTP1 polymorphism in exon 5 (Ile105→Val) in 100 COPD patients and 100 age- and sex-matched healthy controls.Results The proportion of mEH exon 3 heterozygotes was significantly higher in patients with COPD than that in the control subjects (42% vs 32% ). The odds ratio (OR) adjusted by age, sex, body mass index (BMI) and cigarette years was 2.96 (95% CI 1.24 - 7. 09). There was no marked difference in very slow activity genotype versus other genotypes between COPD patients and the controls. When COPD patients were non-smokers, the OR of very slow activity genotype versus other genotypes was more than 1.00; and when COPD patients were smokers ( current smokers and exsmokers), the OR was less than 1.00. There was no significant difference in GSTP1 polymorphism adjusted by age, sex, BMI and smoking between COPD patients and the controls.Conclusions mEH exon 3 heterozygotes might be associated with susceptibility to COPD in China.The interaction might exist between mEH genotype and smoke. The gene polymorphism for GSTP1 might not be associated with susceptibility to COPD in the Chinese population.     

Effects of single nucleotide polymorphisms 869 T/C and 915 G/C in the exon 1 locus of transforming growth factor-β1 gene on chronic obstructive pulmonary disease susceptibility in Chinese

Background The main risk factor for chronic obstructive pulmonary disease （COPD） is cigarette smoking. However, only 10%-20% of chronic heavy smokers develop systematic COPD. We hypothesized that the inheritance of gene polymorphisms could influence the development of COPD, which was investigated by studying two single nucleotide polymorphisms （SNP） in exon 1 of the transforming growth factor-β1 （TGF-β1） gene. Methods We enrolled 219 patients with COPD as the research group and 148 healthy people as the control group, all of whom were Chinese Han people. The polymorphisms of the TGF-β1 gene, 869T/C and 915G/C, were analyzed using the method of amplification refractory mutation system-polymerase chain reaction （ARMS-PCR）. Results The occurrence of the TGF-β1 gene 869T/C polymorphism in patients with COPD was significantly different from the control group （P 〈0.05）, in which the relative risk of this disease increased in cases who had the C allele （OR： 1.131, 95% CI： 1.101-1.539）. There was no increased frequency of TGF-β1 915G/C gene in COPD patients compared with control subjects （P 〉0.05）. Conclusions The polymorphism 869T/C in TGF-β1 gene has a significant association with disease occurrence in COPD patients and the C allele might be a risk factor. The homozygous wild-type CC of 869T/C on TGFβ1 could be a predisposing factor in COPD and those who carry the C allele might have particularly susceptibility to developing COPD.     

Point Mutation in the Parkin Gene on Patients with Parkinson''''s Disease

Summary;To investigate the distribution of possible novel mutations from parkin gene in variant sub-set of patients with Parkinson’s disease(PD)in China and explore whether parkin gene plays an im-portant role in the pathogenesis of PD,70 patients were divided into early-onset group and late-onsetgroup; 70 healthy subjects were included as controls.Genomic DNA from 70 normal controls andfrom those of PD patients were extracted from peripheral blood leukocytes by using standard proce-dures.Mutations of parkin gene(exon 1—12)in all the subjects were screened by PCR-single strandconformation polymorphism(SSCP),and further sequencing was performed in tue samples with ab-normal SSCP results,in order to confirm the mutation and its location.A new missense mutationGly284Arg in a patient and 3 abnormal bands in SSCP electrophoresis from samples of another 3 pa-tients were found.All the DNA variants were sourced from the samples of the patients with early-on-set PD.It was concluded that Parkin point mutation a     

Osteopontin gene polymorphism in association with systemic lupus erythematosus in Chinese patients

Background Osteopontin (OPN) is one kind of cytokine which can play a number of roles in promoting activation of T lymphocyte, regulating balance between Th1 and Th2, participating in cell-induced immunologic response and stimulating B lymphocyte to express multi-clone antibodies. Some researches have showed that OPN may be involved in the pathogenesis of systemic lupus erythematosus (SLE). The aim of this study was to investigate possible association of a single nucleotide polymorphism（SNP）at position 9250 in exon 7 of the OPN gene (OPN gene 9250) with SLE in Chinese patients.Methods Totally 158 patients (18 males and 140 females) fulfilled the revised criteria for SLE by the American College of Rheumatology in 1982 and 180 healthy volunteer controls (34 males and 146 females), all from the south of China, consented to participate in the study. OPN gene 9250 polymorphism was detected by polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP).Results The frequency of TT genotype of the OPN gene 9250 was significantly lower (52.5% vs 70%, P<0.05) and the frequency of TC genotype of the OPN gene 9250 was significantly higher (43.7% vs 29.4%, P<0.05) in SLE patients than in controls. There were significant differences in OPN gene 9250 allele and phenotype frequencies between the SLE patients and controls (P<0.05). When the SLE patients and controls were separated into men and women, significant differences of frequencies were noted in TT genotype, TC genotype and allele of the OPN gene 9250 in women (P<0.05) but not in men (P>0.05). Conclusions OPN gene 9250 polymorphism appears to be associated with susceptibility to SLE in Chinese Han ethnic population.