Significant Differences In Genotype Frequencies Research Articles

Single Nucletide Polymorphisms in Gene of IL-1Beta in Bronchial Asthma

ABSTRACTBronchial asthma is a common chronic lung disease that is driven by abnormal inflammatory reactions in the airways in response to the complex interaction between genetics and environmental factors. The underlying inflammation in asthma is manifested by prominent eosinophil infiltration and Th2 inflammatory mediators; however the pro-inflammatory cytokines, particularly IL-1β, have also been found in increased amount in the sputum and BAL in individuals with bronchial asthma, especially in more severe state. Therefore, IL-1β is considered to be of importance in pathogenesis of this condition as the protein level of the cytokine is finely regulated by variety of factors, including genetics. The IL1B gene displays many SNPs both in promoter and coding regions, which have been associated with IL-1β production.In the current case-control study we investigated -511C>T (rs16944) promoter polymorphism and +3953C>T (rs1143634) silent polymorphism in exon 5 of IL1B and their haplotypes as candidate risk factors of Bronchial asthma in Bulgarian population.We genotyped 47 patients with bronchial asthma and 174 control individuals using Taqman genotyping assay for IL1B -511C>T SNP and PCR-RFLP-based method for +3953C>TSNP.We did not observe statistically significant differences in genotype frequencies of IL1B -511C>T and IL1B +3953C>T between controls and patients with asthma (p=0.065 and p=0.987). However, the minor T allele of IL1B -511C>T was less frequently found in the controls (0.305) compared to the patients with asthma (0.415, p=0.0002). Carriers of IL1B -511T allele (TT or TC genotypes) appeared to have 2.25-fold higher risk for Bronchial asthma (95% CI: 1.127–4.498, p=0.019). The performed estimations of IL1B haplotypes did not reveal any difference in the haplotype frequencies between controls and patients with asthma (p=0.270). However, the T_C haplotype, constructed by alleles found to determine enhanced expression of IL-1β, appeared to be associated with higher risk of asthma (OR 1.78, 1.04–3.03, p=0.035) compared to the most common C_C haplotype.Based on the results of the current study we suggest that the -511C>T promoter polymorphism and +3953C>T silent polymorphism in exon 5 of IL1B may influence the genetic predisposition of Bronchial asthma in Bulgarian population, as the carriers of alleles and haplotypes supposed to define higher IL-1β protein levels are more susceptible for this lung diseases.

Association study between G-protein β3 subunit gene polymorphism and antipsychotic agent-induced obesity

Objective To explore the relationship between G-protein β3 subunit (GNB3) gene C825T polymorphism and antipsychotic agent-induced obesity.Methods 126 schizophrenic inpatients with long-term antipsychotics treatment were collected.According to body mass index ( BMI),patients were divided into obesity group ( n =62) and non-obesity group ( n =64).The GNB3 gene C825T polymorphism was detected by polymerase chain reaction and DNA sequencing technique.Levels of fasting blood glucose,2-hour postprandial blood glucose,blood lipids and blood uric acid of all patients were routinely measured.Results (1)The GNB3 gene C825T polymorphism were found in obesity group and non-obesity group respectively,and the distribution of genotypes in two groups were both consistent with Hardy-Weinberg equilibrium.(2)There was no significant difference in genotype frequencies between obesity group ( CC 17.75％,CT 58.06％,TT 24.19％ ) and non-obesity group( CC 18.75％,CT 62.50％,T T 18.75％ )( x2 =0.59,P ＞ 0.05 ).There was also no significant difference in allele frequencies between obesity group ( C 46.77％,T 53.23 ％ ) and non-obesity group ( C 50％,T 50％ ) ( x2 =0.26,P ＞ 0.05 ).(3)No significant differences were observed in BMI,fasting blood glucose,2-hour postprandial blood glucose,blood lipids and blood uric acid among different genotype groups (all P ＞ 0.05 ).Also no significant differences were observed in BMI,fasting blood glucose,2-hour postprandial blood glucose,blood lipids and blood uric acid between Tallele carrier (TT and CT genotypes) and T-allele non-carrier( CC genotype) ( all P ＞ 0.05 ).Conclusion The GNB3 gene C825T polymorphism may not be a genetic risk factor for antipsychotic agent-induced obesity. Key words: G-protein β3 subunit ; Genetics; Polymorphism; Antipsychotic agents; Obesity

Genetic contribution to C-reactive protein levels in severe obesity

Obese individuals are characterized by a chronic, low-grade inflammatory state. Increased levels of C-reactive protein (CRP), a marker of inflammation, have been observed in subjects with the metabolic syndrome. We have previously reported that genes encoding proteins involved in the anti-inflammatory and immune response are differentially expressed in visceral adipose tissue of obese men with or without the metabolic syndrome. Among these genes, the interferon-gamma-inducible protein 30 (IFI30), CD163 molecule (CD163), chemokine (C-X-C motif) ligand 9 (CXCL9) and thymic stromal lymphopoietin (TSLP), were selected for further genetic analyses. The aim of the study was to verify whether IFI30, CD163, CXCL9 and TSLP gene polymorphisms contribute to explain the inter-individual variability of the inflammatory profile of obesity assessed by plasma high-sensitivity CRP concentrations. A total of 1185 severely obese individuals were genotyped for single nucleotide polymorphisms (SNPs) covering most of the sequence-derived genetic variability at the IFI30, CD163, CXCL9 and TSLP gene loci (total of 27 SNPs). Following measurement of plasma CRP levels, subjects were divided into two groups, low vs. high using the median value of plasma CRP levels (8.31mg/L) as a cutoff point. Genotype frequencies were compared between groups. Associations between genotypes and plasma CRP levels (continuous variable) were also tested after adjustments for age, sex, smoking and BMI. The rs11554159 and rs7125 IFI30 SNPs showed a significant difference in genotype frequencies (p<0.05) between subgroups of low vs. high plasma CRP levels (wild type homozygotes: rs11554159=47% vs. 55%, rs7125=31% vs. 24%, for low vs. high CRP groups, respectively). The association between rs11554159 and CRP levels as a continuous variable remained significant (p=0.004). Both carriers of the GA and AA genotypes demonstrated, on average, a 13% lower CRP levels in comparison with GG homozygotes. No association was observed between SNPs in the CD163, CXCL9 and TSLP genes and CRP levels. The IFI30 rs11554159 polymorphism could partially explain the inter-individual variability observed in the inflammatory profile associated with obesity.

Association of Clusterin Gene Polymorphisms with Late-Onset Alzheimer’s Disease

Background/Aims: Some studies have implicated the role of apolipoprotein J [clusterin (CLU), apoJ] in the pathogenesis of Alzheimer’s disease (AD). In this study, we investigated the polymorphisms rs11136000 and rs9331888 within CLU in late-onset sporadic AD (LOAD) patients and nondemented subjects. Methods: LOAD patients and control subjects were analyzed. Genotyping of rs11136000 and rs9331888 was performed using standard PCR following different restriction endonuclease digestion. Results: Although there were no significant differences in genotype frequencies of these two polymorphisms, the haplotype CG was associated with a statistically significantly increased LOAD risk. Conclusion: The rs11136000 and rs9331888 polymorphisms of the CLU gene are associated with LOAD.

Genetic Variation in the NBS1 Gene Is Associated with Hepatic Cancer Risk in a Chinese Population

NBS1 plays important roles in maintaining genomic stability as a key DNA repair protein in the homologous recombination repair pathway and as a signal modifier in the intra-S phase checkpoint. We hypothesized that polymorphisms of NBS1 are associated with hepatic cancer (HCC) risk. The NBS1 rs1805794 C/G polymorphism has been frequently studied in some cancers with discordant results, but its association with HCC has not been investigated. Moreover, studies of the 3'UTR variant rs2735383 have not touched upon HCC. This study examined the contribution of these two polymorphisms to the risk of developing HCC in a Chinese population. NBS1 genotypes were determined in 865 HCC patients and 900 controls and the associations with risk of HCC were estimated by logistic regression. Compared with the rs1805794 GG genotype, the GC genotype had a significantly increased risk of HCC (adjusted odds ratios [OR]=1.41; 95% confidence interval [CI]=1.11-1.80), the CC carriers had a further increased risk of HCC (OR=2.27; 95% CI=1.68-3.14), and there was a trend for an allele dose effect on risk of HCC (p<0.001). Also, we found that the risk effect of rs1805794 CC+CG was more pronounced in HCC patients that drank (OR=2.28, 95% CI=1.55-3.29 for drinkers; OR=1.31, 95% CI=1.00-1.77 for nondrinkers). However, there was no significant difference in genotype frequencies of rs2735383 G/C site between cases and controls. These findings suggest that rs1805794 C/G polymorphism in NBS1 may be a genetic modifier for developing HCC.

COL6A1Gene and Ironman Triathlon Performance

Mutations in the type VI collagen gene ( COL6A1) cause myopathy and muscle weakness. In addition, COL6A1 knockout mice were shown to have impaired running performance and reduced muscle strength. The COL6A1 rs35796750 polymorphism (IVS32-29 T/C) has been associated with complex phenotypes. The aim of this study was therefore to determine if this polymorphism is associated with performance during the 226 km Ironman triathlon. Participants (n=661) were recruited during 4 South African Ironman triathlons. Finishing times for the 3.8 km swim, 180 km bike, 42.2 km run, and overall race were provided by the race organisers. All participants were genotyped for the COL6A1 rs35796750 polymorphism. Participants with the COL6A1 TT genotype were significantly faster during the bike (p=0.014) and overall race (p=0.030). When participants were grouped into fast, middle and slow bike finishing time tertiles, there was a significant linear trend for the TT genotype (Fast: TT=35.7%; Middle: TT=29.0%; Slow: TT=23.8%; p=0.008). No significant genotype frequency differences were observed for the swim or run of the triathlon. In conclusion, the COL6A1 gene is therefore a potential marker for endurance cycling performance. These effects may be mediated through changes to the composition of type VI collagen containing tissues, such as muscle and tendon.

Susceptibility Loci for Polycystic Ovary Syndrome on Chromosome 2p16.3, 2p21, and 9q33.3 in a Cohort of Caucasian Women

In a recent genome-wide association study investigating Han Chinese PCOS women 3 loci that are strongly associated with PCOS were identified on chromosome 2p16.3 (rs13405728), 2p21 (rs13429458), and 9q33.3 (rs2479106). The aim of the study was to investigate the impact of rs13405728, rs13429458, and rs2479106 variants on PCOS susceptibility in a Caucasian cohort of PCOS and control women. Metabolic, endocrine, and anthropometric measurements and oral glucose tolerance tests were performed in 545 PCOS and 317 control women. The rs13405728, rs13429458, and rs2479106 polymorphisms were genotyped. There was no significant difference in genotype frequencies of rs13405728 and rs13429458 variants between PCOS and controls. There was a trend towards an association of the rs2479106 variant with PCOS susceptibility (p=0.053). PCOS women with the rs2479106 GG genotype had significantly higher WHR than PCOS women carrying the AG and AA genotype (p=0.034 and p=0.020, respectively). Moreover, QChol/HDL and LDL levels were significantly higher in PCOS women carrying the rs2479106 GG genotype when compared to those carrying the AA genotype (p=0.024 and p=0.035, respectively). PCOS women carrying the G allele of rs13405728 had significantly higher AUCgluc, glucose-30 min, and AUCins levels than those carrying the AA genotype (p=0.039, p=0.047, and p=0.044, respectively). In PCOS women, rs13405728 genotypes are associated with glucose and insulin metabolism. Moreover, rs2479106 genotypes were associated with increased WHR levels and an adverse serum lipid profile. Further, we observed a trend towards decreased PCOS susceptibility within carriers of the rs2479106 G-allele. Further studies in large Caucasian PCOS cohorts are warranted to confirm our findings.

Association of the MDR1 3435 polymorphism in patients with refractory rheumatoid arthritis in a Chinese population

To evaluate whether the multidrug resistance gene 1 (MDR1) exon 26 polymorphisms are associated with the refractory rheumatoid arthritis (RRA). The study was carried out on two hundred and twenty-three patients with RA treated and one hundred and three normal controls. The RA treated were divided into two groups according the response to disease-modifying antirheumatic drugs (DMARDs). There were 108 patients in the effective group and 115 patients in the ineffective group. Genotypes of the C3435T polymorphism were determined by polymerase chain reaction followed by restriction digestion (PCR-RFLP). There were significant differences in the genotype frequency and allele frequency among three groups. Compared to responders and controls, the nonresponders carried more CC genotype (χ(2) = 5.306, P = 0.021; χ(2) = 7.810, P = 0.005) and more C allele (χ(2) = 6.601, P = 0.010; χ(2) = 12.172, P = 0.000). But, there were no statistically significant differences in genotype nor allele frequency between RA and healthy controls. The results from our study suggest that the C3435T MDR1 gene polymorphism may not be related with the RA susceptibility, but may influence the efficacy of RA therapy with DMARDs, and the 3435CC genotype may be related with RRA.

Importance of gene variants and co-factors of folate metabolic pathway in the etiology of idiopathic intellectual disability

Different components of the folate metabolic cycle are crucial for maintaining integrity of DNA. The present study was aimed at exploring the role of some important constituents of the folate cycle in the etiology of idiopathic intellectual disability (IID). Nuclear families with IID probands (n = 226) and ethnically matched controls (n = 181) were recruited for micronucleus, karyotype, genetic polymorphism (MTR rs1805087, MTRR rs1801394, and DHFR rs70991108), folate, vitamin B6, vitamin B12, and cysteine analysis. Significant difference in genotype frequencies in IID probands and their parents were observed for rs1805087 (P = 0.03, 0.02), rs1801394 (P = 0.03, 0.001), and rs70991108 ((P = 0.03, 0.02) as compared to controls. IID probands showed significantly higher micronucleus frequency (P = 0.01) and decreased vitamin B6 level (P = 0.002). A strong correlation between rs1801394 ‘G’ allele and micronucleus was also noticed. From the present investigation, a role of genetic polymorphisms and vitamin B6 levels could be hypothesized in the etiology of IID.

Association of COL9A2 gene polymorphism with degenerative disc disease of lumbar in Chinese Han population

Objective To investigate the association between COL9A2 gene polymorphism with lumbar degenerative disc disease (DDD) in Chinese Han population. Methods A total of 125 DDD patients (58 males and 67 femals, aged 51.8 + 10. 6), and 126 controls matched in sex and age (64 males,62 femals, aged 45.7 + 8. 2) were recruited in the case-control study. Peripheral blood was collected for DNA isolation. Results Based on NCBI Genebank, corresponding single nucleotide polymorphisms-SNP1 ( rs12722877), SNP2 ( rs3737820), SNP3 (rs209914) and SNP4 (rs6676013) were identified. Hardy-Weinberg equilibrium was analyzed in both case and control groups. Genotying of all selected SNPs was done by SNPstream technology. The association analysis between phenotyepes and SNPs was conducted.Reslults NPI (rs12722877), SNP2 (rs3737820), SNP3 (rs209914) and SNP4 (rs6676013) were genttyped, and the polymorphisms distributed in line with Hardy-Weinberg equilibrium in case and contral groups. There was no significant difference in allele frequency of SNP1C, SNPIG, SNP2A, SNP2T,SNP3A, SNP3C, SNP4C and SNP4T between case group (91%, 93%, 86%, 89%, 95%, 94%, 12%,and 10%, respectively) and control group (9%, 7%, 14%, 11%, 5%, 6%, 88%, and 90% respectively). No significant difference in genotype frequencies of SNP was found between case group and control group, too (all P＞0.05). Conclusion COL9A2 gene may not be associated with lumbar DDD in ChineseHan population. Key words: Lumbar; Degenerative disc disease; Gene polymorphism

Further evidence for association of polymorphisms in theCNR1gene with cocaine addiction: confirmation in an independent sample and meta-analysis

Genetic research on cocaine dependence (CD) may help clarify our understanding of the disorder as well as provide insights for effective treatment. As endocannabinoid signaling and dopamine neurotransmission have been shown to be involved in drug reward, genes related to these systems are plausible candidates for susceptibility to CD. The cannabinoid receptor 1 protein regulates both the endocannabinoid and dopaminergic neurobiological systems, and polymorphisms in the cannabinoid receptor gene, CNR1, have been associated previously with substance dependence. In this study, we attempt to replicate findings associating CNR1 with CD in African Americans. Cocaine-addicted individuals (n=860) and unaffected controls (n=334) of African descent were genotyped for two single nucleotide polymorphisms (SNPs) in CNR1 (rs6454674, rs806368). We observed a significant difference in genotype frequencies between cases and controls for both SNPs (P≤0.042). A meta-analysis was also performed combining our data with that of Zuo et al. who also studied these polymorphisms in African American cocaine addicts (total n=1253 cases versus 543 controls). When our data were combined, rs6454674 increased in significance to P=0.027; however, rs806368 was no longer significant. This study confirms the association between rs6454674 and CD. However, because there is considerable co-morbidity of CD with other drugs of abuse, additional studies are necessary to determine whether polymorphisms in CNR1 induce a general susceptibility to substance dependence or are specific to cocaine addiction. Furthermore, as this population consists of American individuals of African descent, the possibility of population stratification should not be excluded.

Hypoxia‐inducible factor‐1α polymorphisms are associated with genetic aberrations in lung cancer

The transcription factor, hypoxia-inducible factor-1 (HIF-1), is a master regulator of hypoxia, including repression of DNA repair systems, resulting in genomic instability in cancer cells. The roles of the polymorphic HIF-1α variants, C1772T (P582S) and G1790A (A588T), which are known to enhance transcriptional activity, were evaluated in lung cancers. HIF-1α polymorphisms were assessed by direct sequencing in a total of 83 lung cancer patients (42 adenocarcinomas, 30 squamous cell, four adenosquamous cell and seven small cell lung carcinomas) and in 110 healthy control subjects. The relationship between these polymorphisms and the frequently observed genetic and/or epigenetic aberrations, TP53 loss of heterozygosity (LOH), 1p34 LOH, retinoblastoma-1 (RB1) LOH, p16 inactivation and epidermal growth factor receptor aberrations, was then assessed. There were no significant differences in genotype frequencies for either C1772T or G1790A between lung cancer patients and healthy controls. However, the frequency of the HIF1A C1772T variant allele was significantly higher in lung cancer patients with TP53 LOH (P = 0.015). Among adenocarcinoma patients, individuals with variant alleles of either polymorphism showed significantly higher frequencies of TP53 LOH (P = 0.047), 1p34 LOH (P = 0.009), or either of these (P = 0.008) in the tumours. The in vitro transcriptional activity of these HIF1A variants in A549 lung cancer cells was significantly greater than that of the wild type under either normoxic or hypoxic conditions, especially for P582S in cells containing mutant p53 (P < 0.0005 and P < 0.005, respectively). These findings indicate that functional polymorphisms in the HIF-1α gene may have an important impact on lung carcinogenesis, especially in adenocarcinomas, possibly by increasing genomic instability.

Functional NBS1 polymorphism is associated with occurrence and advanced disease status of nasopharyngeal carcinoma

As a component of the MRN (MRE11/RAD50/NBS1) complex, NBS1 plays an important role in cellular response to DNA damage and the maintenance of chromosomal integrity. The NBS1 E185Q polymorphism (8360G>C, rs1805794) has been frequently studied in some cancers with discordant results, but its association with nasopharyngeal carcinoma (NPC) in Chinese population has not been investigated. Moreover, there is no report about the association between NBS1 3'UTR variant rs2735383 and the risk of NPC. A multiple center case-control analysis was performed to assess the association between NBS1 polymorphisms and NPC risk in Eastern and Southern Chinese population. The genotypes and haplotypes were determined in 1052 cases and 1168 controls and the associations with risk of NPC were estimated by logistic regression. Cell migration assays were performed in 24-well transwell chambers to detect the effects of NBS1 E185Q SNP on cell migration. We observed significant difference in genotype frequencies at the rs1805794 C/G site between cases and controls (P(trend) < 0.0001). The C allele increases the risk for invasive disease or metastatic disease, compared with G allele. More over, CNE-2 cells (NPC cell line) transfected with pcDNA-NBS1-185Q (8360CC) had significantly higher migration levels than those transfected with pcDNA-NBS1-185E (8360GG) (P = 0.024). These findings suggest that E185Q polymorphism in NBS1 may be a genetic modifier for the occurrence and aggression of NPC.

Association of SPINK5 gene polymorphisms with atopic dermatitis in Northeast China

Defect in the SPINK5 gene is known to be implicated in Netherton syndrome (NS), and has been suggested to be a locus predisposing to atopy in general. Coding polymorphisms in SPINK5 exons 13, 14 and 26 have been reported to be associated with atopic dermatitis (AD), asthma and high level of IgE. To examine whether the SPINK5 gene polymorphisms are associated with AD in Northeast China, and to assess how variants influence selected phenotypic traits. A case-control study was conducted on four non-synonymous polymorphisms in the coding region of SPINK5 in AD and controls. The SPINK5 gene polymorphisms were analyzed using the PCR and RFLP methods. For the four non-synonymous SNPs, A1103G(Asn368Ser), G1156A(Asp386Asn), G1258A(Glu420Lys), G2475T(Glu825Asp) in SPINK5, the allelic frequencies in the AD cohort were 0.55 for 1103G, 0.57 for 1156A, 0.54for 1258A, 0.62 for 2475T, consistent with those already published in the original British and Japanese cohorts. The T allele of SNP 2475G > T was found to be significantly associated with AD. There were significant differences in genotype frequencies for G1258A(Glu420Lys) and G2475T(Glu825Asp) but not for A1103G(Asn368Ser) and G1156A(Asp386Asn). Genotypes GA(420Glu/Lys), TT (2475Asp/Asp) and GT(2475Glu/Asp) were significantly more frequent in AD. However, the SPINK5 gene polymorphisms was found not to be associated with AD in regard to either serum IgE levels, concurrent allergic asthma or early onset of AD. Our study confirms the association between SPINK5 and AD.

Association of polymorphism in the serotonin transporter gene promote with the susceptibility to alcohol dependence in Yunnan Han Population

To explore the association of polymorphism in the serotonin transporter gene and the susceptibility to alcohol dependence in Yunnan Han population, PCR and DNA sequencing techniques were used to detect 5-HTT-linked promoter region (5-HTTLPR). One hundred and eighteen alcohol dependent patients as case group and 214 normal people as control group were employed in this study. Significant differences in genotype frequencies were present between case group and control group of 5-HTTLPR (P<0.05). The proportion of L/L and L/S genotype was significantly smaller in case group than that was in control group (OR=0.581, P=0.026). No significant association was observed in allelic frequencies, which differed in different ethnic groups. In conclusion, 5-HTTLPR polymorphism may be associated with alcohol dependent patients, and the genotype L/L or L/S may be a genetic factor that is responsible for decreasing susceptibility of alcohol dependence in Yunnan Han population.

Association of NAT2 Polymorphisms with Type 2 Diabetes in a Population from Bosnia and Herzegovina

N-acetyltransferase 2 (NAT2) is a drug-metabolizing enzyme, which is genetically variable in human populations. Polymorphisms in the NAT2 gene have been associated with drug efficacy and toxicity as well as disease susceptibility. Recently, an association of NAT2 gene variation with risk of type 2 diabetes mellitus (T2DM) has been suggested. This is the first study performed in a population from Bosnia and Herzegovina (BH) in which the frequency of two common NAT2 polymorphisms, 341T>C (NAT2*5) and 590G>A (NAT2*6) was determined in diabetic patients. The frequency of the NAT2*5 (341T>C) and NAT2*6 (590G>A) polymorphisms was analyzed by employing TaqMan SNP Genotyping Assays (Applied Biosystems) in a group of 63 patients with T2DM and 79 nondiabetic subjects. Our data demonstrated that the frequencies of NAT2*5 (341T>C) and NAT2*6 (590G>A) polymorphisms in BH population were in line with the Caucasians genotype data. The NAT2*5 and NAT2*6 alleles were in high linkage disequilibrium (D' = 0.969). Strinkingly, there was a significant difference in genotype frequencies for NAT2*5 (p <0.05) and NAT2*6 (p <0.001) polymorphisms between diabetic and nondiabetic subjects. NAT2*5 polymorphism was associated with 2.4-fold increased risk for developing T2DM (adjusted OR = 2.40, 95% CI = 1.10-5.25, p = 0.028). On the contrary, NAT2*6 variant significantly decreased by 5-fold susceptibility to the disease (adjusted OR = 0.20, 95% CI = 0.09-0.43, p <0.001). Our data demonstrated that NAT2 genetic variation appeared to be an important risk factor in development of T2DM.

Association of the C3 gene polymorphisms with susceptibility to adult asthma

To investigate the association between single nucleotide polymorphisms (SNPs) of the complement component 3 gene (C3) and adult asthma of Hans in southern China. A case-control study was performed. Four hundred and eighty-four adult asthma patients diagnosed in Nanfang Hospital and Affiliated Hospital of Guangdong Medical College, and 553 healthy subjects were collected from 2006 to 2010 for the study. MassARRAY-IPLEX and matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF-MS) techniques was used to determine the genotypes of the rs10402876 and rs366510 loci of C3 gene. Genotypes GG, GT and TT in the rs366510 locus, and genotypes GG, GT and TT in the rs10402876 locus were detected. A total of 98.94 percent of samples were genotyped. There were no significant differences in genotype frequencies (chi-square =0.346,P=0.841) and allele frequencies (chi-square =0.101,P=0.751) of rs10402876 between the two groups. However, genotype and allele frequencies of the rs366510 locus were significantly different (chi-square =9.759, P=0.008, Bonferroni correction, P=0.016; chi-square =5.294,P=0.021, Bonferroni correction, P=0.042, respectively). Compared with genotypes GG+GT, genotype TT of rs366510 significantly increased the risk of asthma, with the odds ratio of 1.471 (95% confidence interval 1.125-1.923). These results suggest that C3 gene could be associated with adult asthma of Han population in southern China.

Filaggrin polymorphism P478S, IgE level, and atopic phenotypes

Whether environmental exposures may modulate the effect of the skin barrier gene on atopic dermatitis (AD) remains to be elucidated. To determine whether filaggrin (FLG) variants can serve as a predictor for atopic disorders in Chinese individuals and if allergen exposures may modify the effect of FLG variants on AD by total IgE levels. In total, 116 children aged 2-5years with AD and 212 control subjects were analysed for the FLG variants using DNA sequencing. Multiple logistic regression models were performed to estimate the association among FLG polymorphisms and atopic phenotypes. Serum total IgE level, standing for the degree of allergen exposures, was later stratified to determine the effects of FLG polymorphisms on AD. A significant difference in genotype frequency was found among AD cases and controls in FLG P478S polymorphism. FLG P478S GG genotype significantly increased the risk of AD [odds ratio (OR) 4·60, 95% confidence interval (CI) 1·88-11·24]. In addition, among subjects with AD, GG genotypes also significantly increased the risk of developing asthma (OR 4·68, 95% CI 1·37-16·03). Further, a similar result was obtained for allergic rhinitis (OR 3·23, 95% CI 1·01-10·30). Interestingly, the P478S GG genotype was significantly related to AD (OR 5·67, 95% CI 1·93-16·60) in children with IgE level ≥100 kU L(-1) . However, the association was not evident when IgE level was < 100 kU L(-1) . Our results suggest that the FLG P478S polymorphism may confer susceptibility to the development of AD among Chinese individuals and may be modified by IgE levels.

Association between male infertility and genetic variability at the PON1/2 and GSTM1/T1 gene loci

Environmental xenobiotics such as organophosphate pesticides are known factors involved in male infertility. Paraoxanase (PON) and glutathione transferase (GST) are involved in biotransformation of organophosphate pesticides. Interindividual genetic variations in biotransformation enzyme activities can lead to differences in the susceptibility to male infertility. This case-control study investigated associations between polymorphisms in the PON and GST genes (PON1–55/192, PON2–311, GSTM1/T1) and infertility. The study group consisted of 187 infertile men (86 with non-obstructive azoospermia (NOA) and 101 with oligoasthenoteratozoospermia (OAT)), whereas the control group comprised of 194 fertile men. Statistically significant differences were found in PON1–55MM genotype (chi-squared = 7.37; P = 0.02) and PON1–55M allele (chi-squared = 5.98; P = 0.01) distribution between the infertile and fertile men. A separate analysis revealed that significant differences in genotype frequencies were limited to the OAT group (chi-squared = 9.11, P = 0.01). However, no significant differences in genotype frequencies of other tested polymorphisms (PON1–192, PON2–311, GSTM1/T1) and male infertility were observed. The PON1–55M allele might represent a risk factor for infertility susceptibility in Slovenian men. Further studies with a larger sample size are needed to confirm these findings. Male infertility affects approximately 10% of the male adult population. Environmental xenobiotics such as organophosphate pesticides are known factors involved in male infertility. Enzymes, like paraoxanase (PON) and glutathione transferase (GST) are involved in the biotransformation of organophosphate pesticides. Therefore interindividual genetic variations in biotransformation enzyme activities can lead to differences in the susceptibility to male infertility. We conducted a case–control study to investigate the association between polymorphisms in the PON and GST genes (PON1–55/192, PON2–311, GSTM1/T1) and infertility in 381 Slovene Caucasian men. The study group consisted of 187 infertile men: 86 with non-obstructive azoospermia and 101 with oligoasthenoteratozoospermia, whereas the control group comprised of 194 proven fertile men. We found statistically significant differences in the PON1–55 genotype (chi-squared (2 df) = 7.37; p = 0.02) and allele (chi-squared (1 df) = 5.98; P = 0.01) distribution between the infertile and fertile men; a separate analysis of patients with azoospermia and oligoasthenoteratozoospermia revealed that significant differences in genotype frequencies were limited to the oligoasthenoteratozoospermia group (chi-squared = 9.11, P = 0.01), which also after applying Benjamini-Hochberg correction remained significant. No significant differences in frequencies of genotypes of other tested polymorphisms (PON1–192, PON2–311, GSTM1/T1) and male infertility were observed. This case–control study found that the PON1–55M allele might represent a risk factor for infertility susceptibility in Slovenian men. Further studies on larger sample size are needed to confirm our findings.

Polimorfismo -174 G/C del gen promotor de interleuquina 6 en mujeres con diabetes mellitus tipo 1

A polymorphism located in the promoter region (-174 G/C) of interleukin 6 (IL-6) has been linked to early onset of type 1 diabetes (T1D) and increased body mass index (BMI).To evaluate the possible association of this -IL-6 gene 174 GIC polymorphism with T1D, BMI and metabolic control in T1D patients in a case-control study.-174 G I C polymorphisms were analyzed by polymerase chain reaction and restriction fragment length polymorphism in 145 women with T1D and 103 healthy controls. BMI and BMI-Z-scores were tabulated and metabolic control was recorded.There was a higher frequency for the C allele in T1D patients compared with the control group (21% versus 14.1%, p = 0.047). No significant differences in genotype frequencies for the -174 GIC polymorphism of IL-6 gene between patients with T1D and controls, were observed. There were no significant associations with T1D and BMI.A higher frequency of C allele in women with T1D was the only finding in this series, suggesting that the polymorphic variant is not related to weight gain in these patients.