THE +1245G/T POLYMORPHISMS IN THE COLLAGEN TYPE I ALPHA 1 (COL1A1) GENE IN POLISH SKIERS WITH ANTERIOR CRUCIATE LIGAMENT INJURY

Objectives

The aim of this study was to examine the association of +1245G/T polymorphisms in the COL1A1 gene with ACL ruptures in Polish male recreational skiers in a case-control study.

Methods

A total of 138 male recreational skiers with surgically diagnosed primary ACL ruptures, all of whom qualified for ligament reconstruction, were recruited for this study. The control group comprised 183 apparently healthy male skiers with a comparable level of exposure to ACL injury, none of whom had any self-reported history of ligament or tendon injury. DNA samples extracted from the oral epithelial cells were genotyped for the +1245G/T polymorphisms using real-time PCR method.

Results

Genotype distributions among cases and controls conformed to Hardy-Weinberg equilibrium (p = 0.2469 and p = 0.33, respectively). There was a significant difference in the genotype distribution between skiers and controls (p = 0.045, Fisher''s exact test). There was no statistical difference in allele distribution: OR 1.43 (0.91-2.25), p = 0.101 (two-sided Fisher''s exact test).

Conclusions

The risk of ACL ruptures was around 1.43 times lower in carriers of a minor allele G as compared to carriers of the allele T.     

A case-control study of anterior cruciate ligament volume,tibial plateau slopes and intercondylar notch dimensions in ACL-injured knees

The role played by anatomical factors in ACL injury remains elusive. In this study, objective methods were used to characterize ACL volume, tibial slopes and notch geometry from ACL-injured and matched-control subjects. The study tested four hypotheses: (1) the medial tibial plateau slope is steeper posteriorly in the injured group compared to the non-injured group, (2) the lateral tibial plateau slope is steeper posteriorly in the injured group compared to the non-injured group, (3) the femoral intercondylar notch dimensions are smaller in the injured group compared to the non-injured group and (4) the ACL volume, tibial plateau slopes and intercondylar notch dimensions are all independent of each other. Fifty-four subjects were divided into two groups, those who had suffered a non-contact ACL injury and those who still had two healthy ACLs, matched to the injured subjects by gender, age, height and weight. The lateral tibial plateaus in the uninjured contralateral knees of the injured subjects had a significantly steeper posterior slope (1.8° vs. ?0.3°), a factor that potentially contributed to the ACL injury in the opposite knee. The intercondylar notch dimensions were found to be smaller in the injured subjects, potentially putting the ACL at risk of impingement, and intercondylar notch volume was correlated to ACL volume (r=0.58). Discriminant analysis showed that the notch width at the inlet was the best single predictor of ACL injury.     

Association Study of Single Nucleotide Polymorphisms in XRCC1 Gene with the Risk of Gastric Cancer in Chinese Population

Gastric cancer is one of highly cancer-related deaths in the world. Previous evidence suggests that the X-ray repair cross-complementing group 1 gene (XRCC1) is one of the most important candidate genes for influencing gastric cancer risk. The objective of this study was to detect the potential association of genetic variants in XRCC1 gene with gastric cancer risk in Chinese Han population. In total, we enrolled 395 gastric cancer patients and 398 cancer-free controls in this study. The genotyping of c.910A>G and c.1804C>A genetic variants in XRCC1 gene were investigate by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and created restriction site-PCR (CRS-PCR) methods, respectively. We found the genotypes/alleles from these two genetic variants were statistically associated with the increased risk of gastric cancer (for c.910A>G, GG versus (vs.) AA: OR = 2.00, 95% CI 1.21-3.31; AG vs. AA: OR = 1.50, 95% CI 1.12-2.02; GG/AG vs. AA: OR = 1.59, 95% CI 1.20-2.10; GG vs. AG/AA: OR = 1.68, 95% CI 1.03-2.73; G vs. A: OR = 1.47, 95% CI 1.18-1.83; for c.1804C>A, AA vs. CC: OR = 2.68, 95% CI 1.46-4.94; AA vs. CA/CC: OR = 2.62, 95% CI 1.44-4.76; A vs. C: OR = 1.33, 95% CI 1.06-1.66). The allele-G of c.910A>G and allele-A of c.1804C>A genetic variants may contribute to gastric cancer susceptibility. These preliminary results indicate that these XRCC1 genetic variants are potentially related to gastric cancer susceptibility in Chinese Han population, and might be used as molecular markers.     

Relationship between Interleukin-10 ?1082A/G Polymorphism and Risk of Ischemic Stroke: A Meta-Analysis

Objective

To analyze the association between −1082A/G polymorphism in interleukin-10 (IL-10) gene and ischemic stroke (IS) risk by meta-analysis.

Methods

We carried out a systematic electronic search in PubMed, BIOSIS Previews, Science Direct, Chinese National Knowledge Infrastructure, Chinese Biomedical Database, Weipu database and WANGFANG Database. Pooled odds ratios (ORs) with 95% confidence intervals (95%CIs) were calculated to assess the strength of the association.

Results

7 studies were included. There was no significant association between IL-10 −1082A/G polymorphism and IS risk under all genetic models in overall estimates (A vs. G: OR = 1.23,95%CI = 0.85–1.79;AA vs. GG: OR = 1.01,95%CI = 0.47–2.19; AG vs. GG: OR = 0.76, 95%CI = 0.38–1.55; AA+AG vs. GG: OR = 0.89,95%CI = 0.46–1.73; AA vs. AG+GG: OR = 1.39, 95%CI = 0.91–2.13). Similarly, no associations were found in subgroup analysis based on ethnicity and source of controls. However, removing the study deviating from Hardy–Weinberg equilibrium (HWE) produced statistically significant associations for overall estimates under recessive model(AA VS. AG+GG OR 1.58, 95% CI 1.04–2.42) and among Asians in all genetic models (A VS.G OR 1.64, 95% CI 1.07–2.53; AA vs. GG OR1.91, 95% CI 1.31–2.80; AG vs. GG OR1.44, 95% CI 1.09–1.91; AA+AG vs. GG OR 1.54, 95% CI 1.18–2.01;AA VS. AG+GG OR 1.79, 95% CI 1.07–3.00). Even after Bonferroni correction, the associations were observed still significantly in Asians under the two models (AA vs. GG OR1.91, 95% CI 1.31–2.80, P = 0.0008; AA+AG vs. GG OR 1.54, 95% CI 1.18–2.01, P = 0.001).

Conclusion

This meta-analysis indicates that IL10 −1082 A/G polymorphism is associated with IS susceptibility in Asians and the −1082 A allele may increase risk of IS in Asians. Considering the sample size is small and between-study heterogeneity is remarkable, more studies with subtle design are warranted in future.     

Association between matrix metalloproteinase-3 polymorphism and anterior cruciate ligament ruptures

Anterior cruciate ligament (ACL) ruptures are considered to be the most severe joint injury in sports. However, the precise etiologies of ACL injuries are not fully understood. Recently, the gene encoding the matrix metalloproteinase-3 (MMP-3, stromelysin-1) was shown to be associated with anterior cruciate ligament ruptures. The 5A/6A polymorphism in the promoter of the MMP-3 gene affects the regulation of MMP-3 gene expression. We examined the association between polymorphism within -1612 of the MMP-3 gene and ACL rupture in an independent population. Eighty-six participants between 20 and 40 years of age with surgically diagnosed ACL ruptures and 100 healthy controls between 18 and 28 years of age without history of ligament or tendon injuries were recruited for the study. All participants were genotyped for the MMP-3 polymorphism (-1612 5A/6A). Statistical analyses of genotype frequencies between patients and healthy controls were performed by the chi-square test. A significant difference was found between ACL rupture subgroups in terms of genotype association (5A+ (5A/5A, 5A/6A): 37.5% in contact sports vs 20% in non-contact sports; P = 0.02). In allelic association, there were significant differences (6A: 81.2% in contact sports vs 89.1% in non-contact sports, 5A: 18.8% in contact sports vs 10.9% in non-contact sports, P = 0.01). The 5A+ genotype of MMP-3 was represented in ACL ruptures in contact sport participants. We propose that this sequence variant is a specific genetic element that should be included in a multifactorial model to understand the etiologies and risk factors for ACL rupture.     

Association of XRCC1 Arg399Gln polymorphism with bladder cancer susceptibility: A meta-analysis

Genetic variations in DNA repair genes are thought to modify DNA repair capacity and may to be related to cancer susceptibility. However, epidemiological study results have been inconsistent. In this meta-analysis, we assessed 24 case–control studies of association between the X-ray repair cross complementing group 1 (XRCC1) Arg399Gln polymorphism and bladder cancer susceptibility in the general population and in Asian and non-Asian subgroups. A moderately significant association with bladder cancer risk was found for AG vs GG (OR = 1.110, 95% CI = 1.018–1.210). No significant associations with bladder cancer risk were found for AA vs GG (OR = 0.942, 95% CI = 0.823–1.077), the dominant model AA/AG vs GG (OR = 1.075, 95% CI = 0.990–1.167) and the recessive model AA vs AG/GG(OR = 0.890, 95% CI = 0.788–1.005). In subgroup analysis, a moderately significant association was also found for AG vs GG (OR = 1.091, 95% CI = 1.008–1.180) in non-Asian subgroup. The analysis suggests that the XRCC1 Arg399Gln polymorphism might be a moderate risk factor for bladder cancer, especially in non-Asian population.     

Quantitative assessment of the association between TAP2 rs241447 polymorphism and cancer risk

The findings regarding the relation of transporter associated with antigen processing (TAP) to cancer risk have been inconsistent. The aim of this study was to comprehensively evaluate the association between TAP2 rs241447 polymorphism and cancer susceptibility. A meta-analysis of nine investigations with 2800 cases and 1620 controls was conducted to gain a better understanding of the effect of TAP2 rs241447 polymorphism on cancer risk. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to evaluate the strength of the correlation between TAP2 gene polymorphism and cancer susceptibility. The pooled results from TAP2 rs241447 polymorphism showed a decreased risk of cancer in two dominant genetic models (GG + AG vs AA: OR = 0.86, 95% CI, 0.75-0.99; AG vs AA: OR = 0.85, 95% CI, 0.73-0.99). From the subgroup analysis, decreased cancer susceptibility was found in Caucasians (GG + AG vs AA: OR = 0.82, 95% CI, 0.68-0.99), especially among the subgroup of cervical carcinoma (GG + AG vs AA: OR = 0.82, 95% CI, 0.69-0.96; AG vs AA: OR = 0.83, 95% CI, 0.70-0.99). Overall, the results suggest that TAP2 rs241447 polymorphism contributes to decreased cancer susceptibility.     

Associations of Genetic Variants in the PSCA,MUC1 and PLCE1 Genes with Stomach Cancer Susceptibility in a Chinese Population

BackgroundSeveral genetic variants including PSCA rs2294008 C>T and rs2976392 G>A, MUC1 rs4072037 T>C, and PLCE1 rs2274223 A>G have shown significant association with stomach cancer risk in the previous genome-wide association studies (GWASs).MethodsTo evaluate associations of these SNPs in the Han Chinese, an independent hospital based case-control study was performed by genotyping these four polymorphisms in a total of 692 stomach cancer cases and 774 healthy controls acquired by using frequency matching for age and gender. False-positive report probability (FPRP) analysis was also performed to validate all statistically significant findings.ResultsIn the current study, significant association with stomach cancer susceptibility was observed for all the four polymorphisms of interest. Specifically, a significant increased stomach cancer risk was associated with PSCA rs2294008 (CT vs. CC: adjusted OR = 1.37, 95% CI = 1.07–1.74, and CT/TT vs.CC: adjusted OR = 1.30, 95% CI = 1.03–1.63), PSCA rs2976392 (AG vs. GG: adjusted OR = 1.30, 95% CI = 1.02–1.65, and AG/AA vs. GG: adjusted OR = 1.26, 95% CI = 1.00–1.59), or PLCE1 rs2274223 (AG vs. AA: adjusted OR = 1.48, 95% CI = 1.15–1.90, and AG/GG vs. AA: adjusted OR = 1.45, 95% CI = 1.14–1.84), respectively. In contrast, MUC1 rs4072037 was shown to decrease the cancer risk (CT vs. TT: adjusted OR = 0.77, 95% CI = 0.60–0.98). Patients with more than one risk genotypes had significant increased risk to develop stomach cancer (adjusted OR = 1.30, 95% CI = 1.03–1.64), when compared with those having 0–1 risk genotypes. Stratified analysis indicated that the increased risk was more pronounced in younger subjects, men, ever smokers, smokers with pack years ≤ 27, patients with high BMI, or non-cardia stomach cancer.ConclusionsThis study substantiated the associations between four previous reported genetic variants and stomach cancer susceptibility in an independent Han Chinese population. Further studies with larger sample size and different ethnicities are warranted to validate our findings.     

CYP2D6*4 Allele Polymorphism Increases the Risk of Parkinson’s Disease: Evidence from Meta-Analysis

Background

Many epidemiological studies have been conducted to explore the association between a single CYP2D6 gene polymorphism and Parkinson’s disease (PD) susceptibility. However, the results remain controversial.

Objectives

To clarify the effects of a single CYP2D6 gene polymorphism on the risk of PD, a meta-analysis of all available studies relating to CYP2D6*4 polymorphism and the risk of PD was conducted.

Methods

A comprehensive literature search of PubMed, EMBASE, and the China National Knowledge Infrastructure (CNKI) up to September 1, 2013 was conducted. Data were extracted by two independent authors and pooled odds ratio (OR) with 95% confidence interval (CI) were calculated. Meta-regression, Galbraith plots, subgroup analysis, sensitivity analysis, and publication bias analysis were also performed.

Results

Twenty-two separate comparisons consisting of 2,629 patients and 3,601 controls were included in our meta-analysis. The pooled analyses showed a significant association between CYP2D6*4G/A polymorphism and PD risk in all of the comparisons (A vs. G allele: OR = 1.28, 95% CI = 1.14–1.43, P = 0.001; AA vs. GG: OR = 1.43, 95% CI = 1.06–1.93, P = 0.018; AG vs. GG: OR = 1.22, 95% CI = 1.06–1.40, P = 0.006; AG+AA vs. GG: OR = 1.26, 95% CI = 1.10–1.44, P = 0.001; AA vs. AG+GG: OR = 1.37, 95% CI = 1.02–1.83, P = 0.036). In subgroup analysis stratified by ethnicity, significant associations were also demonstrated in Caucasians but not in Asians. No significant association was found in subgroup analysis stratified by age of onset or disease form.

Conclusions

We concluded that the CYP2D6*4G/A polymorphism denotes an increased genetic susceptibility to PD in the overall population, especially in Caucasians. Further large and well-designed studies are needed to confirm this association.     

Association of SNP rs6903956 on chromosome 6p24.1 with angiographical characteristics of coronary atherosclerosis in a chinese population

Objective

To explore the association between rs6903956 and severity of coronary artery disease (CAD) in a Chinese population.

Methods

A cohort of 1075 consecutive patients who underwent coronary arteriography for suspected or known coronary atherosclerosis was enrolled in our study. Coronary atherosclerosis severity was defined by Gensini''s Score System and counts of diseased vessels.

Results

Gensini score frequencies and counts of diseased vessels differed among GG, AG, AA genotype groups at the rs6903956 locus (p = 0.025 for Gensini score frequencies vs. p = 0.024 for counts of diseased vessels, respectively). A univariate logistic regression analysis revealed that the genotype distribution of this SNP was associated significantly with angiographical characteristics of coronary atherosclerosis risk (p = 0.030, odds ratio (OR) = 1.444, 95% confidence interval (CI) = 1.036∼2.013 for AG vs. GG; p = 0.021, OR = 5.896, 95% CI = 1.299∼26.750 for AA vs. GG and p = 0.007, OR = 1.564, 95% CI = 1.132∼2.162 for combined (AG+AA) vs. GG). A multivariate logistic regression analysis indicated that the genotype distribution of the rs6903956 polymorphism be associated significantly with the angiographical characteristics of coronary atherosclerosis risk (p = 0.004, OR = 1.578, 95% CI = 1.155∼2.154 for GG vs. AG vs. AA; p = 0.013, OR = 1.541, 95% CI = 1.097∼2.163 for GG vs. GA+ AA). A stratification analysis revealed that male subjects and smoking subjects had a higher frequency of the rs6903956 heterozygous mutant among higher Gensini score subjects than among lower Gensini score subjects (p = 0.023, OR = 1.579, 95% CI = 1.064∼2.344 for male subgroup; p = 0.005, OR = 2.075, 95% CI = 1.249∼3.448 for smoking subgroup).

Conclusions

Allele A is a risk factor for CAD and the G-to-A allele substitution may underlie the association between rs6903956 and CAD.     

BTNL2 Gene Polymorphism and Sarcoidosis Susceptibility: A Meta-Analysis

Background

Butyrophilin-like 2 (BTNL2) rs2076530 gene polymorphism has been implicated in susceptibility to sarcoidosis. However, results from previous studies are not consistent. To assess the association of BTNL2 polymorphism and sarcoidosis susceptibility, a meta-analysis was performed.

Methods

PubMed, Embase were searched for eligible case-control studies. Data were extracted and pooled odds ratios (OR) with 95% confidence intervals (CI) were calculated.

Results

Ten studies involving a total of 3303 cases and 2514 controls were included in this meta-analysis. Combined data indicated that BTNL2 rs2076530 polymorphism was associated with sarcoidosis susceptibility in allelic model (A vs. G, OR = 1.59, 95%CI: 1.47–1.72), dominant model (AA + AG vs. GG, OR = 2.10, 95%CI: 1.67–2.65), and recessive model (AA vs. AG + GG, OR = 1.93, 95%CI: 1.49–2.50).

Conclusions

This meta-analysis indicates that BTNL2 rs2076530 polymorphism contributes to the risk of sarcoidosis.     

Variant in sulfonylurea receptor-1 gene is associated with high insulin concentrations in non-diabetic Mexican Americans: SUR-1 gene variant and hyperinsulinemia

The high-affinity sulfonylurea receptor (SUR1) gene regulates insulin secretion and may play a role in type 2 diabetes. A silent variant in exon 31 of SUR1 (AGG→AGA) was detected by single-strand conformational polymorphism and genotypes were determined for 396 Mexican American subjects (289 non-diabetic). The normal and mutant alleles were designated G and A, respectively. Among non-diabetics, those with the AA genotype had higher fasting insulin values than those with the AG and GG genotypes (113.4 pmol/l for AA vs 82.8 pmol/l for AG/GG, P=0.043). Similar results were observed for 2-h insulin (849.6 pmοl/l for AA vs 498.6 pmol/l for AG/GG, P=0.0003) and for the proinsulin to specific insulin ratio (0.068 for AA vs 0.056 for AG/GG, P=0.030). Specific insulin levels also differed significantly across the three genotypic classes (P=0.021). No differences in fasting glucose, body mass index, or waist circumference according to genotype were noted. Two-hour glucose was modestly higher in individuals with the AA genotype. Since we have previously reported linkage between SUR1 and hyperglycemia, the present association between a SUR1 variant and hyperinsulinemia in normal individuals from a high diabetes risk ethnic group raises the possibility of primary insulin hypersecretion as an antecedent of type 2 diabetes in at least some individuals from this population. Received: 3 April 1998 / Accepted: 5 June 1998     

Programmed Cell Death-1 Polymorphisms Decrease the Cancer Risk: A Meta-Analysis Involving Twelve Case-Control Studies

Programmed cell death-1 (PD-1) plays an important inhibitory role in anti-tumor responses, so it is considered as a powerful candidate gene for individual’s genetic susceptibility to cancer. Recently, some epidemiological studies have evaluated the association between PD-1 polymorphisms and cancer risk. However, the results of the studies are conflicting. Therefore, a meta-analysis was performed. We identified all studies reporting the relationship between PD-1 polymorphisms and cancers by electronically searches. According to the inclusion criteria and the quality assessment of Newcastle-Ottawa Scale (NOS), only high quality studies were included. A total of twelve relevant studies involving 5,206 cases and 5,174 controls were recruited. For PD-1.5 (rs2227981) polymorphism, significantly decreased cancer risks were obtained among overall population, Asians subgroup and population-based subgroup both in TT vs. CC and TT vs. CT+CC genetic models. In addition, a similar result was also found in T vs. C allele for overall population. However, there were no significant associations between either PD-1.9 (rs2227982) or PD-1 rs7421861 polymorphisms and cancer risks in all genetic models and alleles. For PD-1.3 (rs11568821) polymorphism, we found different cancer susceptibilities between GA vs. GG and AA vs. AG+GG genetic models, and no associations between AA vs. GG, AA+AG vs. GG genetic models or A vs. G allele and cancer risks. In general, our results firstly indicated that PD-1.5 (rs2227981) polymorphism is associated a strongly decreased risk of cancers. Additional epidemiological studies are needed to confirm our findings.     

Association study of microRNA polymorphisms with risk of idiopathic recurrent spontaneous abortion in Korean women

Aim

The aim of this study was to investigate the association of microRNA polymorphisms (miR-146aC>G, miR-149T>C, miR-196a2T>C, and miR-499A>G) in Korean patients with recurrent spontaneous abortion (RSA).

Methods

We conducted a case-control study of 564 Korean women: 330 patients with at least two unexplained consecutive pregnancy losses and 234 healthy controls with at least one live birth and no history of pregnancy loss.

Results

RSA patients exhibited significantly different frequencies of the miR-196a2CC (TT+TC vs. CC; adjusted odds ratio [AOR], 1.587; 95% confidence interval [CI], 1.042-2.417) and miR-499AG+GG genotypes (AOR, 1.671; 95% CI, 1.054-2.651) compared with the control group. The combination of miR-196a2CC and miR-499AG+GG showed synergistic effects (AOR, 3.541; 95% CI, 1.645-7.624).

Conclusion

miR-196a2CC, miR-499AG+GG, and the miR-196a2CC/miR-499AG+GG combination are significantly associated with idiopathic RSA in Korean women.     

Quadriceps and hamstrings prelanding myoelectric activity during landing from different heights among male and female athletes

ACL tear is a major concern among athletes, coaches and sports scientists. More than taking the athlete away from training and competition, ACL tear is a risk factor for early-onset of knee osteoarthritis, and, therefore addressing strategies to avoid such injury is pertinent not only for competitive athletes, but for all physically active subjects. Imbalances in the prelanding myoelectric activity of the hamstrings and quadriceps muscles have been linked to ACL injuries. We investigated the effect of landing from different heights on prelanding myoelectric activity of the hamstrings and quadriceps muscles in recreational athletes. Thirty recreational athletes (15 male and 15 female) performed three bilateral drop jumps from two different heights; 20 cm and 40 cm while myoelectric activity of the vastus medialis, rectus femoris, biceps femoris and medial hamstrings were collected. When increasing the height of drop landing tasks prelanding normalized myoelectric activity of the quadriceps was increased by 15–20% but no significant changes were found for the hamstrings. Female athletes exhibited higher activity of the medial hamstrings compared to their male counterparts. We concluded that increasing the height of drop landing tasks is associated with increased myoelectric activity of the quadriceps but not the hamstrings in recreational athletes. These differences in muscle activity may be related to increased risk for ACL injury when the height is increased. Female athletes demonstrated higher recruitment of the medial hamstrings.     

Next-Generation Sequencing of Connective Tissue Genes in Patients with Classical Ehlers-Danlos Syndrome

Background: Ehlers-Danlos syndrome (EDS) is a common non-inflammatory, congenital connective tissue disorder. Classical type (cEDS) EDS is one of the more common forms, typically caused by mutations in the COL5A1 and COL5A2 genes, though causative mutations in the COL1A1 gene have also been described. Material and methods: The study group included 59 patients of Polish origin, diagnosed with cEDS. The analysis was performed on genomic DNA (gDNA) with NGS technology, using an Illumina sequencer. Thirty-five genes related to connective tissue were investigated. The pathogenicity of the detected variants was assessed by VarSome. Results: The NGS of 35 genes revealed variants within the COL5A1, COL5A2, COL1A1, and COL1A2 genes for 30 of the 59 patients investigated. Our panel detected no sequence variations for the remaining 29 patients. Discussion: Next-generation sequencing, with an appropriate multigene panel, showed great potential to assist in the diagnosis of EDS and other connective tissue disorders. Our data also show that not all causative genes giving rise to cEDS have been elucidated yet.     

rs4215 SNP in zinc-α2-glycoprotein gene is associated with obesity in Chinese north Han population

Objective

Zinc-α2-glycoprotein (ZAG) has been identified recently as a novel adipokine due to its close link with lipid and glucose metabolism, as well as regulation of body weight. The aim of our present study is to investigate the ZAG genetic polymorphism association with obesity in Chinese north Han population.

Design and methods

Five SNPs of ZAG gene including rs2247607 (A>T), rs4727442 (G>T), rs4215 (A>G), rs2527923 (C>T) and rs2527882 (C>T) were genotyped in 648 overweight/obese patients and 313 healthy controls by TaqMan-PCR methods. Crosstabs statistical analysis method with subjects stratifying by age (≦ 30 y, 31–45 y, ≧ 46 y) and gender was used.

Results

The results showed the constitution of three genotype frequencies in rs4215 (A>G) site significantly differs in male subgroup (aged 31–45 y) between overweight/obese and healthy control group (χ² = 6.401, P = 0.041). GG genotype frequency in overweight/obese group is 19.3% which is much higher than 6.1% in healthy control group. Further statistical analysis under a recessive inheritance model demonstrated odd ratio (OR) for GG vs. AA+AG in overweight/obese group was 3.674 (95% CI 1.049–12.866; P = 0.035). Among three genotypes of rs4215, the subjects with GG genotype have much more higher body weight, BMI, waist circumference and SBP.

Conclusion

Our data, for the first time, suggest the genotypes of rs4215 in ZAG gene are significantly associated with obesity in Chinese north Han population. GG genotype subjects in rs4215 site have an increased susceptibility to obesity when compared with the AA+AG genotype subjects.     

Association study of the β2-adrenergic receptor gene polymorphisms and hypertension in the Northern Han Chinese

Background

The β2-adrenergic receptor (ADRB2) gene has been widely researched as a candidate gene for essential hypertension (EH), but no consensus has been reached in different ethnicities. The aim of the present study was to evaluate the possible association between the ADRB2 gene polymorphisms and the EH risk in the Northern Han Chinese population.

Methodology/Principal Findings

This study included 747 hypertensive subjects and 390 healthy volunteers as control subjects in the Northern Han Chinese. Genotyping was performed to identify the C-47T, A46G and C79G polymorphisms of the ADRB2 gene. G allelic frequency of A46G polymorphism was significantly higher in hypertensive subjects (P = 0.011, OR = 1.287, 95%CI [1.059–1.565]) than that in controls. Significant association could also be found in dominant genetic model (GG+AG vs. AA, P = 0.006, OR = 1.497, 95%CI [1.121–1.998]), in homozygote comparison (GG vs. AA, P = 0.025, OR = 1.568, 95%CI [1.059–2.322]), and in additive genetic model (GG vs. AG vs. AA, P = 0.012, OR = 1.282, 95%CI [1.056–1.555]). Subgroup analyses performed by gender suggested that this association could be found in male, but not in female. Stratification analyses by obesity showed that A46G polymorphism was related to the prevalence of hypertension in the obese population (GG vs. AG vs. AA, P<0.001, OR = 1.645, 95%CI [1.258–2.151]). Significant interaction was found between A46G genotypes and body mass index on EH risk. No significant association could be found between C-47T or C79G polymorphism and EH risk. Linkage disequilibrium was detected between the C-47T, A46G and C79G polymorphisms. Haplotype analyses observed that the T-47-A46-C79 haplotype was a protective haplotype for EH, while the T-47-G46-C79 haplotype increased the risk.

Conclusions/Significances

We revealed that the ADRB2 A46G polymorphism might increase the risk for EH in the Northern Han Chinese population.