Sex-specific association of the SPTY2D1 rs7934205 polymorphism and serum lipid levels

The objective of the present study was to detect the association of the rs7934205 single nucleotide polymorphism (SNP) near the Suppressor of Ty, domain containing 1 gene (SPTY2D1) and serum lipid levels between males and females in the Mulao and Han populations. Genotyping of SPTY2D1 rs7934205 SNP was performed in 933 of Mulao and 865 of Han participants using polymerase chain reaction and restriction fragment length polymorphism. The T allele frequency was different between Mulao males and females (23.2% vs. 27.9%, P = 0.018). The genotype and allele frequencies were also different between Han males and females (P = 0.020 and P = 0.004; respectively). Serum levels of apolipoprotein (Apo) A1 in Mulao males; and total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), ApoA1 and ApoB in Mulao females were different between the CC and CT/TT genotypes (P < 0.05). Serum TC, ApoB levels in Han males, and ApoB levels in Han females were different between the CC and CT/TT genotypes (P < 0.05). The subjects with CT/TT genotype in both Mulao and Han males and females have more favorable lipid profiles than those with CC genotype. These findings suggest that the association between the SPTY2D1 rs7934205 SNP and serum lipid levels might have ethnic- and/or sex-specificity.     

Tagging single nucleotide polymorphisms in the PPAR-γ and RXR-α gene and type 2 diabetes risk:a case-control study of a Chinese Han population

Peroxisome proliferator-activated receptor (PPAR-γ),which is mainly involved in adipocyte differentiation, has been suggested to play an important role in the pathogenesis of insulin resistance and atherosclerosis. We investigated the frequencies of two common tagging polymorphisms of the PPAR-γ gene and two of PPAR-α with minor allele frequency (MAF)≥ 0.05 in the Chinese Han population and analyzed the correlation between the different genotypes and the risk of type 2 diabetes mellitus (T2DM). TaqMan assay was performed to test the genotypes in T2DM patients (n = 1,105) and normal controls (n = 1,107). Serum adiponectin concentration was measured by ELISA kit. The variant genotypes rs17817276GG, rs3856806CT and rs3856806CT/TT of PPAR-γ were associated with T2DM, P = 0.023,0.037 and 0.018, respectively. Furthermore, the prevalence of haplotype GT in PPAR-γ was less frequent in the case subjects (0.3%) than in the controls (1.9%) [P < 0.001,OR(95%CI)=0.13 (0.06-0.31)]. Patients with genotype TT of rs3856806 had a higher serum level of adiponectin than those with the genotype CC and CT (P = 0.031 and 0.038, respectively). There was no statistically significant difference between patients and controls in genotype distribution of rs6537944 and rs1045570 of the RXR-α gene. The present study suggests that the variant genotypes in the PPAR-γ gene could decrease the risk for the development of T2DM in the Chinese Han population.     

Association of polymorphism in adiponectin (+45 T/G) and leptin (–2548 G/A) genes with type 2 diabetes mellitus in male Egyptians

Introduction

Adiponectin is an adipose tissue-specific protein with insulin-sensitizing properties. Many investigators have explored the association between adiponectin single nucleotide polymorphisms (SNPs) and type 2 diabetes mellitus (T2DM) in different ethnic populations from different regions. Leptin is a protein hormone constituting an important signal in the regulation of adipose tissue mass and body weight. The aim of this study was to explore potential associations between SNP +45 T>G of the adiponectin gene and SNP 2548G/A of leptin with T2DM and the effect of SNPs on serum adiponectin and leptin levels.

Material and methods

From the Egyptian population, we enrolled 110 T2DM patients and 90 non-diabetic controls. Serum lipid profile, blood glucose, serum adiponectin, and leptin were measured. Genotyping for two common SNPs of the adiponectin and leptin genes was performed by polymerase chain reaction–restriction fragment length polymorphism.

Results

The G allele and TG/GG genotype of SNP 45 occurred more frequently than the T allele and TT genotype in T2DM patients compares to the controls. Subjects with the GG + TG genotype of SNP 45 were at increased risk for T2DM (OR = 6.476; 95% CI: 3.401–12.33) and associated with a low serum adiponectin level compared with the TT genotype. The serum leptin concentration of GA + AA genotype carriers was not significantly different from that of the GG genotype in the diabetic group.

Conclusions

The G allele carriers who have reduced plasma concentrations of adiponectin may have an association with T2DM, while leptin SNP 2548 G/A is not associated with the risk of development of T2DM in the Egyptian population.     

Evidence of association between single-nucleotide polymorphisms in lipid metabolism-related genes and type 2 diabetes mellitus in a Chinese population

Background: Type 2 diabetes mellitus (T2DM) is a complex chronic metabolic disorder triggered by insulin resistance in peripheral tissues. Evidence has shown that lipid metabolism and related genetic factors lead to insulin resistance. Hence, it is meaningful to investigate the association between single-nucleotide polymorphisms (SNPs) in lipid metabolism-related genes and T2DM.Methods: A total of 1,194 subjects with T2DM and 1,274 Non-diabetic subjects (NDM) were enrolled. Five SNPs in three genes (rs864745 in JAZF1, rs35767 in IGF1, and rs4376068, rs4402960, and rs6769511 in IGF2BP2) that contribute to insulin resistance involving lipid metabolism were genotyped using the MassArray method in a Chinese population.Results: The allele and genotypes of rs6769511 in IGF2BP2 were associated with T2DM (P=0.009 and P=0.002, respectively). In inheritance model analysis, compared with the T/T-C/T genotype, the C/C genotype of rs6769511 in IGF2BP2 was a risk factor for the development of T2DM (P<0.001, odds ratio [OR] =1.76; 95% confidence interval [CI]: 1.29-2.42). Haplotype analysis revealed associations of the rs4376068-rs4402960-rs6769511 haplotypes in IGF2BP2 with the development of T2DM (P=0.015). Additionally, rs4376068C-rs4402960T-rs6769511C was a risk haplotype for T2DM (OR=1.179; 95% CI: 1.033-1.346).Conclusion: The rs6769511 in IGF2BP2 was associated with T2DM susceptibility, and the rs4376068-rs4402960-rs6769511 haplotypes in IGF2BP2 was associated with the development of T2DM in a Chinese population.     

Genetic variants of OCT1 influence glycemic response to metformin in Han Chinese patients with type-2 diabetes mellitus in Shanghai

Aims/hypothesis: Genetic variation in OCT1 can influence the glycemic response to metformin. We evaluated the effects of the OCT1 single-nucleotide polymorphisms (SNPs), rs1867351, rs4709400, rs628031, and rs2297374, on metformin efficacy in type-2 diabetes mellitus (DM) patients. Methods: We performed a single-center prospective analysis of the distributions of these SNPs in a cohort of Han Chinese subjects in Shanghai, China (HCS), and evaluated the effects of each SNP on glycemic control in HCS DM patients following 3 months of incident metformin treatment. Results: The allele frequencies of rs4709400 and rs628031 in our HCS control group differed from those previously reported for Han Chinese subjects in Beijing (HCB), as well as those previously reported for Caucasians and Africans, whereas the allele frequencies of rs1867351 and rs2297374 were more similar to those in HCB subjects. The DM patients with the rs1867351 T/T or rs4709400 G/G genotype exhibited greater reductions in postprandial plasma glucose (PPG), compared to those with different genotypes of these SNPs. The DM patients with the rs2297374 C/T, rs4709400 G/G, or rs628031 G/G genotype exhibited greater reductions in fasting plasma glucose (FPG), and those with the rs1867351 T/T, rs628031 A/A, or rs2297374 C/T genotype exhibited greater reductions in HbA_1c , compared to those with different genotypes of these SNPs. Conclusions /interpretation: The rs1867351, rs4709400, rs628031, and rs2297374 SNPs of OCT1 have selective effects on FPG, PPG, and HbA_1c in HCS DM patients in response to metformin treatment. Future studies of these SNPs in larger samples of HCS DM patients are warranted.     

Relevance between HLA-DP gene rs2281388 polymorphism and hepatocellular carcinoma risk

Purpose: We carried out this study to find out the relevance between rs2281388 T/C polymorphism of human leukocyte antigen (HLA) gene and hepatocellular carcinoma (HCC) risk in Chinese Han population. Methods: The method of polymerase chain reaction (PCR) was applied to amplify the genomic DNA. Then the PCR products were sequenced to test the HLA-DP gene rs2281388T/C polymorphism of the case and control groups. Odds ratios (ORs) and 95% confidence interval (95% CIs) were utilized to evaluate the potential correlation between rs2281388 variants and HCC risk. Results: We analyzed the rs2281388 polymorphism distribution among the clinical pathological features. The results showed that there existed a significant statistic correlation between rs2281388T/C polymorphism of HLA-DP gene and HBsAg feature, and no significant correlation was found between rs2281388 and other clinical features. Further analysis showed that the TT genotype of rs2281388 was significantly correlated with HCC risk, and the same to T allele, but there was no significant difference of CT genotype distribution in case and control groups. Conclusion: TT genotype and T allele of HLA-DP gene rs2281388 polymorphism may increase the risk of HCC.     

A Single Nucleotide Polymorphism of IL-21 Gene is Associated with Systemic Lupus Erythematosus in a Chinese Population

The aim of this study was to examine the association of single-nucleotide polymorphisms (SNPs) in IL-21 gene with susceptibility to systemic lupus erythematosus (SLE) in a Chinese population. A total of 605 independent SLE patients and 666 unrelated healthy controls were recruited for the case?Ccontrol association study. Two SNPs (rs2221903 and rs907715) within the IL-21 gene intronic region were genotyped by TaqMan SNP allelic discrimination methods. The allele T frequency of SNP rs2221903 in patients and healthy controls was 89.4?% and 86.8?%, respectively [T versus C, odds ratio (OR)?=?1.287, 95?% confidence interval (CI)?=?1.010?C1.640]. No significant differences in genotype frequencies were shown between SLE patients and healthy controls (P value?=?0.705, 0.406, respectively). However, the effect of recessive model (TT versus CC?+?CT, OR?=?1.368, 95?% CI?=?1.050?C1.781) was observed. Distributions of allele and genotype frequencies of the SNP rs907715 showed no significant differences between SLE patients and controls. Analysis of the haplotypes revealed that CC haplotype was significantly associated with SLE (OR?=?0.734, 95?% CI?=?0.573?C0.941). In conclusion, our findings suggest that a SNP (rs2221903) and CC haplotype (rs2221903 and rs907715) of the IL-21 gene is associated with SLE in the Chinese population. However, further studies are needed to determine the functional consequences of this polymorphism with SLE susceptibility.     

Association of two polymorphisms in the FADS1/FADS2 gene cluster and the risk of coronary artery disease and ischemic stroke

Little is known about the association of the FADS1/FADS2 SNPs and serum lipid levels and the risk of coronary artery disease (CAD) and ischemic stroke (IS) in the Chinese southern population. The present study aimed to determine such association in the Chinese southern population. A total of 1,669 unrelated subjects (CAD, 534; IS, 553; and healthy controls, 582) were recruited in the study. Genotypes of the FADS1 rs174546 SNP and the FADS2 rs174601 SNP were determined by the SNaPshot Multiplex Kit. The T allele and TT genotype frequencies of the two SNPs were predominant in our study population. The T alleles were associated with increased risk of CAD and IS. Correspondingly, the C alleles were associated with reduced risk of CAD and IS. Haplotype analyses showed that the haplotype of T-T (rs174546-rs174601) was associated with an increased risk for IS, and the haplotype of C-C (rs174546-rs174601) was associated with a reduced risk for CAD and IS. The two SNPs were likely to influence serum lipid levels. The T allele carriers of the two SNPs and rs174601 TT genotype were associated with decreased serum HDL-C and ApoAI levels in the patient groups and with an increased risk of CAD and IS. The present study suggests that the FADS1 rs174546 SNP and the FADS2 rs174601 SNP are associated with the risk of CAD and IS, and are likely to influence serum lipid levels. However, further functional studies are needed to clarify how the two SNPs actually affect serum lipid levels and the risk of CAD and IS.     

Association of Genetic Variants of SIRT1 With Type 2 Diabetes Mellitus

SIRT1 has been demonstrated in nutrient-sensing and insulin-signaling pathways in in vivo and in vitro experiments, but there is minimal information concerning the association between gene polymorphisms of SIRT1 and type 2 diabetes mellitus (T2DM) in a Chinese Han population. Using case-control design, we recruited 310 unrelated T2DM patients from inpatients at Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, while 301 healthy controls were volunteers from the community for regular medical checkup. All participants were genotyped within the SIRT1 region. The following five SNPs rs10509291, rs12778366, rs10997870, rs10823112, and rs4746720 cover 100% of common genetic variations (minor allele frequency ≥ 0.05) within the SIRT1 gene (r ² ≥ 0.8). The genotypes of SIRT1 gene polymorphisms were analyzed by the Snapshot assay and DNA sequencing. The resulting data show that there was significant genetic differentiation in rs10823112 [p = 0.003; OR (95% CI) = 1.515 (1.152–1.994) for genotype], rs4746720 [p = 0.024; OR (95% CI) = 1.37 (1.037–1.674) for genotype], and rs10509291 [p = 0.002; OR (95% CI) = 1.551 (1.179–2.04) for genotype] between T2DM and control subjects. However, the result of rs4746720 was no longer significant after correction for multiple testing (p after Bonferroni correction = 0.12); the results of rs10509291and rs10823112 were still significantly different between the two groups (p after Bonferroni correction = 0.01 and 0.015, respectively). Linear regression analyses adjusting for age, gender, and body mass index (BMI) showed that HbA1c and HOMA-IR in subjects with rs10509291 AA genotype were higher than those with TT genotype in T2DM group (p = 0.045, p = 0.035, respectively). Together, our data show that genetic variation of the SIRT1 gene is related to insulin resistance and increase risk of T2DM in Chinese Han population. The risk allele A at SIRT1 rs10509291 was closely associated with T2DM, and subjects who were homozygous of the A allele were more likely to develop T2DM.Key words: Type 2 diabetes, Genetic variants, SIRT1, Chinese Han population     

Polymorphisms in the 5' region of the CD14 gene are associated with eczema in young children

BACKGROUND: Variants in the CD14 gene (CD14) are hypothesized to be associated with atopic disorders. However, most studies have only investigated one polymorphism in this gene. OBJECTIVE: We sought to study the association of 5 single nucleotide polymorphisms (SNPs) in the 5' flanking region of CD14 with eczema and serum IgE levels in young children. METHODS: We genotyped 5 SNPs in an approximately 6.5-kb region in the 5' region of CD14 in 344 2-year-old white children from 2 birth cohorts in the northeastern United States. We examined the relation of both single SNPs and haplotypes in CD14 with the atopic outcomes. RESULTS: Two SNPs were significantly associated with eczema. In dominant models adjusted for potential confounders, SNP rs2569193 was associated with significantly decreased risk for eczema (odds ratio [OR] for CT/TT vs CC, 0.5; 95% CI, 0.3-0.8), whereas SNP rs2569190 (also reported as the C-159T) was associated with significantly increased risk for eczema (OR for CT/TT vs CC, 2.3; 95% CI, 1.4-3.8). The CT/TT genotypes of SNP rs2569190 also had higher geometric means of serum IgE than the CC genotype (24.6 vs 15 IU/mL, P = .025). Haplotype analyses provided results similar to those of the single SNP analyses. CONCLUSIONS: Our results contradict previous reports that have found a protective effect of the T allele of SNP rs2569190 (C-159T) against atopic disorders. Nevertheless, these results confirm the importance of polymorphisms in CD14 in the development of atopy, and future studies of this gene region will need to account for linkage disequilibrium and environmental exposures unique to the study population.     

Interleukin-7 Receptor Single Nucleotide Polymorphism rs6897932 (C/T) and the Susceptibility to Systemic Lupus Erythematosus

Emerging evidences were accumulated to support the view that aberrant interleukin-7 (IL-7) signaling might be associated with autoimmunity. Former studies demonstrated the single nucleotide polymorphism (SNP) rs6897932 C/T in the IL-7 receptor (IL-7R) gene was associated with susceptibility to autoimmune diseases, including multiple sclerosis and type I diabetes. Given these, this study was conducted to investigate whether an association existed between SNP rs6897932 and the susceptibility to systemic lupus erythematosus (SLE), a severe systemic autoimmune disease. In this context, 816 SLE patients and 816 controls from a Chinese population were recruited for this study, and the results showed that the major allele C of rs6897932 showed a higher frequency in SLE patients compared with controls (P?=?0.039, C versus T); significant difference was also detected under a recessive model with regard to the distribution of genotype frequencies between SLE patients and controls (P?=?0.041, CC versus CT + TT), which was not consistent with the results under a dominant model (P?=?0.349, CC + CT versus TT). Moreover, association studies were also performed contraposing the relationship between the SNP rs6897932 C/T and lupus nephritis as well as 10 clinical features of SLE; however, no significant association signal was found regarding the distribution of allele and genotype frequencies between SLE patients positive and negative for the presence of 11 sub-phenotypes. In conclusion, the major allele C of SNP rs6897932 may be associated with increased SLE risk in Chinese populations, and further studies are still encouraged to shed light on the true associations between SLE and its susceptibility genes with respect to IL-7R gene.     

IL28B gene variants and glucose metabolism in Type 2 Diabetes

Type 2 Diabetes (T2D) develops, when β-cell insulin response fails to compensate for insulin resistance. Recent studies reported associations between the IL28B polymorphisms (rs12979860 and rs8099917) and T2D development in Hepatitis C virus (HCV) patients. To identify possible association with T2D independent from virus infection, we investigated both IL28B polymorphisms in T2D patients and healthy controls (HC). No association was found comparing the genotype and allele frequencies of both IL28B polymorphisms between T2D patients and HC. However, higher glucose levels were found in T2D patients carrying the IL28B CT/TT rs12979860 and GT/GG rs8099917 HCV risk genotypes compared to those with the protective CC and TT genotype (p = 0.06 and p = 0.02, respectively). Moreover, T2D patients with CT/TT rs12979860 HCV risk genotypes possessed significantly higher HbA1c levels than CC carriers (p = 0.04). In conclusion, the IL28B HCV risk genotypes may influence glucose homeostasis in T2D patients without HCV.     

成都地区汉族人群PPARGC1A基因Thr394Thr位点G/A多态性与2型糖尿病及胰岛素抵抗的相关性研究

目的 了解中国成都地区汉族人群过氧化物酶体增殖物激活受体γ辅助激活因子-1α基因(peroxisome proliferator-activated receptor gamma,coactivator 1 alpha,PPARGC1A;又名PGC-1α)Thr394Thr位核苷酸G/A的基因型分布,探讨该多态性与2型糖尿病(type 2 diabetes mellitus,T2DM)、胰岛素抵抗及其他代谢异常的关系.方法 应用聚合酶链反应-限制性片段长度多态性技术检测151例无亲缘关系的T2DM患者和156名糖耐量正常对照者PPARGC1A基因Thr394Thr位核苷酸G/A多态性.所有研究对象均测定血糖、胰岛素、血脂,测量身高、体重、腰围、血压.结果 与正常对照组相比,T2DM组的体重指数、腰围、血压、甘油三酯水平均显著增高(P＜0.05),而高密度脂蛋白胆固醇(high density lipoprotein-cholesterol,HDL-C)水平显著降低(P＜0.05).A等位基因的频率在T2DM及正常对照组分别为22.5%、18.6%,AG基因型频率在两组分别为43.7%、37.2%,差异无统计学意义.在T2DM组中,AA+AG基因型的空腹胰岛素、稳态模型评估法胰岛素抵抗指数(homeostasis model aseessment-insulin resistance,HOMA-IR)及腰围明显高于GG基因型,HDL-C显著低于GG基因型(P＜0.05).无论T2DM和正常对照,A等位基因携带者HOMA-IR明显高于GG者.结论 PPARGC1A基因Thr394Thr位核苷酸G/A多态性与胰岛素抵抗存在明显相关,并可能与T2DM患者中心性肥胖及低HDL-C水平相关,其与T2DM发病的关系有待进一步研究.     

ATM基因rs227060位点单核苷酸多态性与肺癌易感性的相关性

目的:探讨共济失调毛细血管扩张症突变基因(ataxia telangiectasia mutated,ATM)rs227060位点单核苷酸多态性(single nucleotide polymorphisms,SNPs)与肺癌易感性之间的相关性.方法:采用聚合酶链反应-SNP敏感性分子开关方法,检测225例肺癌患者和128例健康体检者ATM基因rs227060多态位点等位基因以及基因型频率分布特点;并应用非条件Logistic回归法统计分析rs227060单核苷酸多态性与肺癌的相关性.结果:rs227060多态位点共检测出CC,CT,TT三种基因型和C,T两种等位基因,其在肺癌组与对照组的基因型分布频率为:CC基因型17.3％与29.7％、CT基因型61,4％与59.3％、TT基因型21.3％与11％,两组间基因型频率和等位基因频率分布差异均有统计学意义(P＜0.05).在对ATM rs227060基因型的多态性分析过程中发现:吸烟史在肺癌组与对照组相比差异无统计学意义(P＞0.05),而年龄、性别、肿瘤家族史在肺癌组与对照组相比差异均有统计学意义(P＜0.05);且以CC基因型作为对照,携带TT基因型的个体患肺癌的风险是携带CT基因型个体的3.49倍(OR=1.829;95％CI:1.045～3.199).结论:ATM基因rs227060位点单核苷酸多态性与肺癌易感性存在相关性,且携带TT基因型可增加肺癌的发病风险.     

Association of NOS3 gene variants and clinical contributors of hypoxic-ischemic encephalopathy

The aim of this study was to analyze the association of different clinical contributors of hypoxic-ischemic encephalopathy with NOS3 gene polymorphisms. A total of 110 children with hypoxic-ischemic encephalopathy and 128 control children were selected for this study. Association of gender, gestational age, birth weight, Apgar score, cranial ultrasonography, and magnetic resonance imaging findings with genotypic data of six haplotype-tagging single nucleotide polymorphisms and the most commonly investigated rs1800779 and rs2070744 polymorphisms was analyzed. The TGT haplotype of rs1800783, rs1800779, and rs2070744 polymorphisms was associated with hypoxic-ischemic encephalopathy. Children with the TGT haplotype were infants below 32 weeks of gestation and they had the most severe brain damage. Increased incidence of the TT genotype of the NOS3 rs1808593 SNP was found in the group of hypoxic-ischemic encephalopathy patients with medium and severe brain damage. The probability of brain damage was twice as high in children with the TT genotype than in children with the TG genotype of the same polymorphism. Furthermore, the T allele of the same polymorphism was twice as frequent in children with lower Apgar scores. This study strongly suggests associations of NOS3 gene polymorphism with intensity of brain damage and severity of the clinical picture in affected children.     

AMPKα2基因多态性与2型糖尿病及脂联素、抵抗素的关系

目的 研究甘肃地区汉族人群AMPKα2基因多态性与T2DM、胰岛素抵抗及血清脂联素、抵抗素水平的关系.方法 选取T2DM患者188例和非糖尿病正常人群179例,用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)法,检测AMPK-rs2796516G/A基因型.用酶联免疫法(ELISA)测定血清脂联素、抵抗素浓度,...     

Relationship between the single nucleotide polymorphisms of β2-adrenergic receptor 5’-regulatory region and essential hypertension in Chinese Kazakh ethnic minority group

Objective: To study the correlation of β₂-AR gene 5’-regulatory region SNPs and essential hypertension (EH) in Chinese Kazakh ethnic minority group. Methods: The Sequenom MassArray^® SNP detection technology was used to detect β₂-AR gene 5’-regulatory region SNPs in 150 Xinjiang Kazakh EH patients and 150 controls. Biochemical analyzer was used to detect lipid and other related biochemical parameters. SHEsis and other software were used to analyze linkage disequilibrium and haplotype. Results: Six loci rs205304 (-1023G/A), rs17108803 (-893T/G), rs12654778 (-654G/A), rs11168070 (-468C/G), rs11959427 (-367C/T) and rs2895795 (-1429T/A) polymorphisms of β₂-AR gene 5’-regulatory region were found in the Xinjiang Kazakh populations. While, there was no significant difference between EH group and NH in genotypes and allele frequency of rs2053044, rs12654778, rs2895795, rs17108803 and rs11959427 (P>0.05). However; significant differences were detected of rs11168070 genotypes and allele frequency in two groups (P<0.05). Analysis of the linkage disequilibrium and haplotype in Kazakh population, there is a strong linkage disequilibrium of rs11168070, rs2053044, rs2895795 gene polymorphism in the EH group, and rs11168070, rs12654778, rs17108803 gene polymorphism in controls. Frequency of haplotype GTCCAT, GACTGT and ATGCGT in EH group was higher (P<0.05), while frequency of ATCTGT, ATGTGT, GTCCGT, GTCTAT, GACCAT and GTCTGT in the EH group was significantly lower than the control (P<0.05). Conclusions: β₂-AR gene 5’-regulatory region of rs11168070, rs2053044, rs17108803, rs12654778, rs11959427 and rs2895795 genetic polymorphism exists in Kazakh. Among them, rs11168070 locus genotype and allele frequency distribution in the two groups are significant differences. In six polymorphic loci, there is a strong linkage disequilibrium, which haplotypes GTCCAT, GACTGT, ATGCGT are risk factors of EH, and the ATCTGT, ATGTGT, GTCCGT, GTCTAT, GACCAT, GTCTGT are protective factors.     

Thymic stromal lymphopoietin (TSLP) secretion from human nasal epithelium is a function of TSLP genotype

Recent candidate gene and genome-wide association studies have identified “protective” associations between the single-nucleotide polymorphism (SNP) rs1837253 in the TSLP gene and risk for allergy, asthma, and airway hyperresponsiveness. The absence of linkage disequilibrium of rs1837253 with other SNPs in the region suggests it is likely a causal polymorphism for these associations, having functional consequences. We hypothesized that rs1837253 genotype would influence TSLP secretion from mucosal surfaces. We therefore evaluated the secretion of TSLP protein from primary nasal epithelial cells (NECs) of atopic and nonatopic individuals and its association with rs1837253 genotype. We found that although atopic sensitization does not affect the secretion of TSLP from NECs, there was decreased TSLP secretion in NECs obtained from heterozygous (CT; 1.8-fold) and homozygous minor allele (TT; 2.5-fold) individuals, as compared with NECs from homozygous major allele individuals (CC; P<0.05), after double-stranded RNA (dsRNA) stimulation (50 μg ml⁻¹). Our novel results show that rs1837253 polymorphism may be directly involved in the regulation of TSLP secretion. This may help explain the protective association of this genetic variant with asthma and related traits. Identifying functional consequences of SNPs in genes with previously reported clinical associations is critical in understanding and targeting allergic inflammation.