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 between polymorphisms of platelet membrane glycoprotein Ibα and risk of coronary heart disease in Han Chinese,Henan, China

Objective: To study the relationship between human platelet alloantigens-2 (HPA-2) polymorphism, Kozak sequence polymorphism, macroglycopeptide region variable number of tandem repeats (VNTR) polymorphism of GPIbα and coronary heart disease (CHD). Methods: In the present study, blood obtained from 403 patients with CHD and 500 healthy controls was detected by PCR or PCR-RFLP methods to analyze the genotypes of HPA-2, Kozak sequence and VNTR. Results: About HPA-2 polymorphism, there were significant differences between CHD group and control group in TM+MM genotype (13.15% vs. 8.60%, P < 0.05; OR 1.609; 95% CI 1.051 to 2.463) and M alleles distributions (6.58% vs. 4.40%, P < 0.05; OR 1.645; 95% CI 1.090 to 2.482). For Kozak sequence polymorphism, between control group and CHD group, the difference of CC genotype distribution is statistic significance (3.20% vs. 7.69%, P < 0.05; OR 2.000; 95% CI 1.076 to 3.718). The genotype analysis of VNTR in Han People of Henan (AC, BC, BD, CC, CD and DD) proved that no association between any genotypes or alleles and CHD. There weren’t any significant differences about haplotypes of these genes between control group and CHD group (P > 0.05). Conclusions: The M allele of HPA-2 could be an important risk factor for CHD; the CC genotype of Kozak sequence would be a biomarker of genetic susceptibility about CHD; and each genotype of VNTR is no associated with CHD. No significant differences between control group and CHD group about haplotypes of these genes.     

CXCL12 rs266085 and TNF-α rs1799724 polymorphisms and susceptibility to cervical cancer in a Chinese population

Further research is required to identify single nucleotide polymorphisms (SNPs) associated with cervical cancer. The aim of this study was to assess the association of TNF-α/rs1799724 and CXCL12/rs266085 polymorphisms with susceptibility to cervical cancer in Han Chinese population in Shandong Province. 348 patients with cervical squamous cell carcinoma, including CIS (121) and invasive carcinoma (227), and 351 healthy controls. Genomic DNA was isolated from peripheral blood and genotyping for TNF-α/rs1799724 and CXCL12/rs266085 was carried out using TaqMan SNP Genotyping Assays. TNF-α/rs1799724 polymorphism showed the C-allele was less prevalent among cases as compared to controls (74.3% vs. 92.0%), while the T-allele was more prevalent among cases (P=0.000, OR=3.99, 95% C.I.: 2.90-5.51). CXCL12/rs266085 polymorphism showed the C-allele was less prevalent among cases as compared to controls (41.2% vs. 49.7%), while the T-allele was more prevalent among cases (P=0.001, OR=1.41, 95% C.I.: 1.14-1.74). The genotype and allele frequencies of these two SNPs did not differ between CIS and invasive squamous cell carcinoma (P>0.05). Moreover, the allele frequencies of rs1799724 were significantly different between controls without or with HPV infection (P<0.05). Neither the genotype nor allele frequencies of rs266085 were statistically different between HPV-negative and positive controls. TNF-α/rs1799724 and CXCL12/rs266085 polymorphisms are associated with cervical cancer. C->T polymorphism of these two SNPs and HPV infection are linked to high risk for cervical cancer.     

Application of the back-error propagation artificial neural network （BPANN） on genetic variants in the PPAR-γ and RXR-α gene and risk of metabolic syndrome in a Chinese Han population

This study was aimed to explore the associations between the combined effects of several polymorphisms in the PPAR-γ and RXR-α gene and environmental factors with the risk of metabolic syndrome by back-error propaga- tion artificial neural network （BPANN）. We established the model based on data gathered from metabolic syndrome patients （n = 1012） and normal controls （n = 1069） by BPANN. Mean impact value （MIV） for each input variable was calculated and the sequence of factors was sorted according to their absolute MIVs. Generalized multifactor dimensionality reduction （GMDR） confirmed a joint effect of PPAR-9＂ and RXR-a based on the results from BPANN. By BPANN analysis, the sequences according to the importance of metabolic syndrome risk fac- tors were in the order of body mass index （BMI）, serum adiponectin, rs4240711, gender, rs4842194, family history of type 2 diabetes, rs2920502, physical activity, alcohol drinking, rs3856806, family history of hypertension, rs1045570, rs6537944, age, rs17817276, family history of hyperlipidemia, smoking, rs1801282 and rs3132291. However, no polymorphism was statistically significant in multiple logistic regression analysis. After controlling for environmental factors, A1, A2, B1 and B2 （rs4240711, rs4842194, rs2920502 and rs3856806） models were the best models （cross-validation consistency 10/10, P = 0.0107） with the GMDR method. In conclusion, the interaction of the PPAR-γ and RXR-α gene could play a role in susceptibility to metabolic syndrome. A more realistic model is obtained by using BPANN to screen out determinants of diseases of multiple etiologies like metabolic syndrome.     

<Emphasis Type="Italic">RET</Emphasis> polymorphisms and the risk of Hirschsprung’s disease in a Chinese population

Hirschsprung's disease (HSCR) is a congenital disorder characterized by intestinal obstructions due to the absence of enteric ganglia along variable lengths of the intestinal tract. RET coding mutations have been found in approximately 50% of familial cases, but they only explain a minority of sporadic cases. Here, we report our investigation of a possible role of RET non-coding mutations in sporadic HSCR patients. The haplotypes of seven single nucleotide polymorphisms (SNPs), all located in a region 4 kb upstream of the gene through to 23 kb of intron 1, and one SNP in exon 2 were constructed in 125 Han Chinese patients with sporadic HSCR and in 148 Han Chinese controls. Our results indicated that eight SNPs were significantly associated with HSCR (P < 0.0001). The C allele of rs2505535 would appear to represent a protecting allele for the Chinese population. One single haplotype composed of these eight markers was present in 59.6% of patients, versus 18.1% of controls. Based on our results, we conclude that non-coding mutations in RET have important roles in the development of HSCR. The unknown functional disease variant(s), with a dosage-dependent effect in HSCR, is likely to be located in the 5'-region of the RET gene.     

Relationship of IL-1 and TNF-α polymorphisms with Helicobacter pylori in gastric diseases in a Brazilian population

It is well known that the risk of development of gastric cancer (GC) in Helicobacter pylori-infected patients depends on several factors. Thus, the aim of this study was to investigate the effect of proinflammatory cytokine gene polymorphisms for IL-1β, IL-1RN and TNF-α on the development of GC in a Brazilian population. A total of 202 biopsies obtained from Brazilian patients with chronic gastritis and GC were included in the study. Infection with H. pylori cagA⁺ was determined by the polymerase chain reaction (PCR) as previously described. IL-1β, IL-1RN and TNF-α polymorphism genotyping was performed by restriction fragment length polymorphism PCR. Associations between gene polymorphisms, clinical diseases and virulence markers were evaluated using either the X² test or the Fisher exact test. Our results demonstrated that the IL-1β -511 C/C and IL-1β -511 C/T alleles were associated with chronic gastritis in H. pylori-positive patients (P = 0.04 and P = 0.05, respectively) and the IL-1β -511 C/C genotype was associated with GC (P = 0.03). The frequency of IL-1RN alleles from patients with chronic gastritis and GC indicated that there was no difference between the genotypes of the groups studied. Similar results were found for TNF-α -308 gene polymorphisms. Our results indicate that the IL-1β -511 C/C and C/T gene polymorphisms are associated with chronic gastritis and GC development in H. pylori-infected individuals.     

Association of IL8 -251A/T, IL12B -1188A/C and TNF-α -238A/G polymorphisms with Tourette syndrome in a family-based association study in a Chinese Han population

An earlier study indicated a possible relationship between Tourette syndrome (TS) and the cytokines. To explore this further, we analyzed the association of the polymorphisms, IL8 -251A/T, IL12B -1188A/C and TNF-α -238A/G, in the IL8, IL12B and TNF-α cytokine genes with TS in a Chinese Han population. A total of 108 patients diagnosed with TS and their parents were recruited for the study. The genetic contributions of the IL8 -251A/T, IL12B -1188A/C, and TNF-α -238A/G polymorphisms were evaluated using polymerase chain reaction and restriction enzyme digestion (PCR-RFLP) and haplotype relative risk (HRR) and transmission disequilibrium test (TDT) statistics. Our results revealed no significant associations between the IL8 -251A/T, IL12B -1188A/C and TNF-α -238A/G polymorphisms and TS (for IL8 -251A/T, TDT=0.418, df=1, P=0.518; HRR=2.17, X(2)=3.000, P=0.083, 95%CI: 0.900-5.230; for IL12B -1188A/C, TDT=1.131, df=1, P=0.288; HRR=1.27, X(2)=0.35, P=0.549, 95%CI: 0.580-2.790; for TNF-α -238A/G, TDT=2.793, df=1, P=0.095; HRR=0.27, X(2)=2.90, P=0.089, 95%CI: 0.061-1.217). This result was confirmed using haplotype-based haplotype relative risk (HHRR) which allows the two alleles in each genotype to be considered separately. Our data suggests that the IL-8 -251A/T, IL-12B -1188A/C and TNF-α -238A/G polymorphisms may not be associated with susceptibility to TS in the Chinese Han population studied. However, these results need to be replicated using larger datasets collected from different populations.     

Association of IL-1β and IL-6 gene polymorphisms with recurrent spontaneous abortion in a Chinese Han population

As certain cytokines may play a role in unexplained recurrent spontaneous abortion (RSA) and also some cytokine gene polymorphisms may affect the level of cytokine production, the aim of this study was to investigate the relationship between Chinese RSA and polymorphisms of the genes coding for interleukin (IL)-1β (-31C/T, -511C/T, +3954C/T) and IL-6 (-634C/G). Women (n = 162) with at least three consecutive spontaneous abortions and 156 ethnically matched healthy women with at least one successful pregnancy were included. Genotypes were determined using restriction fragment length polymorphism analysis of polymerase chain reaction products. No significant differences were found in the IL-1β-31T, -511T and +3954T distributions between the RSA group and the control group. On the other hand, the frequencies of the IL-6-634GG genotype and -634G allele were significantly decreased in the RSA group versus the control group (genotype: P = 0.0003; allele: P = 0.002), suggesting the IL-6-634C/G polymorphism might be a possible genetic protective factor for RSA.     

TNF-α promoter single nucleotide polymorphisms and haplotypes associate with susceptibility of immune thrombocytopenia in Chinese adults

Objective

Tumor necrosis factor-alpha (TNF-α) participates as a candidate susceptibility factor for immune thrombocytopenia (ITP). This study attempted to investigate the association between five single nucleotide polymorphisms (SNPs) spanning the TNF-α promoter and the susceptibility of primary ITP in Chinese Han adults.

Methods

In 215 adult primary ITP patients and 206 healthy controls, SNPs were detected by PCR-RFLP and PCR-SSP. The χ² test or fisher’s exact test was used to compare frequencies of genotypes and alleles between patients and controls. Haplotypes were analyzed with the SHEsis online program. TNF-α, IFN-γ and Galectin-9 mRNA of 35 newly diagnosed adult ITP patients and 35 healthy controls were detected by qRT-PCR.

Results

The haplotype GGC (−238G/−308G/−857C) of TNF-α promoter was significantly associated with a decreased susceptibility of primary ITP, especially in males. The relative levels of mRNA expression of TNF-α, IFN-γ and Gal-9 in adult active primary ITP patients was significantly up-regulated compared with patients in remission and controls.

Conclusions

This study represented the first report that the haplotype GGC of TNF-α was differentially associated with the susceptibility of primary ITP in Chinese Han adults. The up-regulation of TNF-α, IFN-γ and Galectin-9 was significantly correlated with active primary ITP in adult patients.     

Single nucleotide polymorphisms of ERβ and coronary atherosclerotic disease in Chinese Han women

Background: Growing evidence has shown that with the increase of age, the incidence of coronary atherosclerotic disease (CAD) in women increases to equal that of men. Several studies on the single nucleotide polymorphisms [SNPs] seem to provide evidence in support of the protective role estrogen receptor β (ERβ) has in reducing the risk of CAD. Objective: To determine the association of ERβ SNPs rs1256049 RsaI 1082 A > G and rs4986938 AluI 1730 G > A with coronary atherosclerotic disease in Chinese Han women. Methods: We designed a nested case-control research, in which 120 case women and 30 control women were selected from the Forensic Medicine Department of Tongji Medical College, HUST. We isolated DNA from their lung paraffin blocks, and then screened for these two SNPs for each DNA sample. Post-statistical analysis of their genotypes and haplotypes was used to figure out the targeted association. Results: We found no significant difference between the genotypes or haplotypes of the two SNPs and the risk of CAD. However, the rs4986938 heterozygote AG variant was correlated with a significantly lower risk for CAD than did homozygote GG variant in the group of less than 40 years old. Haplotype AA of the two SNPs was correlated with a higher risk for CAD in the same group. Conclusion: The rs4986938 AluI 1730 G > A seems to be quite involved in the genetic basis of the disease and needs more attention in future studies. Meanwhile, this very association made between CAD and the mentioned SNP seems to be affected quite a bit by age.     

PPARα polymorphisms as risk factors for dyslipidemia in a Brazilian population

Background and aimsPeroxisome proliferator-activated receptor α is a nuclear receptor involved in the regulation of several biochemical pathways. Polymorphisms within its gene have been associated with several metabolic traits. We aimed to investigate the association of L162V and Intron 7G > C polymorphisms with serum level markers and common morbidities affecting an older adult/elderly cohort from Cuiaba City, Mato Grosso State, Brazil, as well as to compare the results with a previously studied population from São Paulo City, Brazil.Methods and resultsThe studied population consisted of 570 subjects from Cuiaba City, Brazil, who were subjected to clinical interviews and blood collection for laboratory examinations and DNA extraction. Dyslipidemia was defined when participants were taking oral hypolipemiants or those with total cholesterol above 200 mg/dL, HDL-c below 40 mg/dL, LDL-c above 130 mg/dL and TG above 150 mg/dL. Restriction fragment length polymorphism polymerase chain reaction (RFLP-PCR) was used for polymorphism genotyping. Individual polymorphism and haplotype data were available for analyses. In the studied sample, allele frequencies were 0.052 and 0.292 for 162V and Intron 7C, respectively. In brief, 162V allele was associated with dyslipidemia (p = 0.025), and after correction for alcohol consumption and waist-to-rip ratio, a tendency of association could still be observed (p = 0.050). In addition, Intron 7C allele was associated with dyslipidemia even after correction for the same variables (p = 0.029). When compared to our previous study from São Paulo, we found some divergences regarding these results, which may be explained by differences between the two populations. Haplotype association analyses revealed an association between L/C haplotype and dyslipidemia (p = 0.021) and between V/C haplotype and lower LDL-c levels when compared to L/G haplotype (p = 0.044).ConclusionThese results may help to clarify the role of PPARα gene in lipid and lipoprotein metabolism and the evaluation of its polymorphisms and haplotypes as being characterized as genetic risk factors for metabolic disturbances.     

Association study of rs924080 and rs11209032 polymorphisms of IL23R-IL12RB2 in a Northern Chinese Han population with Behcet’s disease

ObjectivesTwo genome-wide association studies (GWAS) have identified the IL-23 receptor- IL-12 receptor β2 (IL23R-IL12RB2) as the susceptibility genetic region in Turkish and Japanese population with Behçet’s disease (BD). We investigated the association of this region with BD in a Northern Chinese Han population.MethodsA total of 407 patients with BD and 421 healthy controls were genotyped for single nucleotide polymorphisms (SNPs) rs924080 and rs11209032 using the Sequenom MassArray system.ResultsStatistically significant associations with BD were detected at two SNPs namely, rs924080 and rs11209032, both, by allele analysis (OR = 1.58, 95% CI = 1.25–2.00, P_c = 2.52 × 10⁻⁴, and OR = 1.45, 95% CI = 1.19–1.76, P_c = 3.46 × 10⁻⁴, respectively), and genotype analysis (P_c = 1.22 × 10⁻³ and P_c = 1.77 × 10⁻³, respectively). Significant differences were observed in the genotype frequency distribution for these SNPs under the additive, dominant and recessive models (all P_c < 0.05). The haplotypes (AT and GC) formed by the two SNPs were associated with BD (all permutation P < 0.05). A meta-analysis also appeared to support the association of the two SNPs with BD.ConclusionSNPs (rs924080 and rs11209032) of the IL23R-IL12RB2 region were found to be associated with BD in a Northern Chinese Han population.     

Genetic association of cyclooxygenase-2 gene polymorphisms with Parkinson’s disease susceptibility in Chinese Han population

Objective: The aim of this study was to explore the genetic association of cyclooxygenase-2 (COX2) gene promoter region polymorphisms with Parkinson’s disease (PD) susceptibility in Chinese Han population. Methods: The genotyping of COX2 gene polymorphisms was conducted by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) in 122 patients with PD and 120 healthy persons. The association strength of gene polymorphism with disease was measured by odds ratio (OR) and 95% confidence interval (95% CI) calculated using χ² test which also evaluated the Hardy-Weinberg equilibrium (HWE) of gene polymorphism in controls. The linkage disequilibrium and haplotype were also analyzed as evidence in the analysis of association. Results: On condition that the genotypes distributions of COX2 -1290A>G, -1195G>A, -765G>C in the control group all conformed to HWE, however, only the homozygous genotype AA of -1195G>A polymorphism showed an association with PD (OR=0.432, 95% CI=0.196-0.950). In addition, in haplotype analysis, G-A-C haplotype frequency in cases was significantly lower than the controls, compared with the common haplotype A-G-G (P=0.031, OR=0.375, 95% CI=0.149-0.940). Conclusions: COX2 -1195G>A polymorphism might play a protective role in the onset of PD and G-A-C haplotype in this three promoter region polymorphisms also showed a negative association.     

PvuII and XbaI polymorphisms of estrogen receptor-α and the results of estroprogestagen therapy in girls with functional hypothalamic amenorrhea – preliminary study

Introduction

The aim of this study was the long-term prospective evaluation of the effects of estroprogestagen (EP) therapy on the bone mineral density (BMD) of girls with functional hypothalamic amenorrhea (FHA) carrying various PvuII and XbaI polymorphisms of ER-α.

Material and methods

Prospective observation included 84 FHA girls and 50 controls. The FHA patients were subjected to 4-year sequential therapy with 17β estradiol (2 mg from the 2^nd to 25^th day of the menstrual cycle) and dydrogesterone (10 mg from the 16^th to the 25^th day). Hormonal parameters, serum concentration of the bone fraction of alkaline phosphatase (BALP), urine concentration of cross-linked n-telopeptide of type I collagen (Ntx) and BMD were determined before and after the treatment.

Results

Six-month treatment resulted in a marked increase in estradiol (p = 0.001), testosterone and prolactin levels (p = 0.01 both) and a significant decrease in BALP and Ntx (p = 0.001 both). Patients with the PP polymorphism had significantly lower baseline BMD compared to carriers of other polymorphic variants of PvuII (p = 0.003). A significant increase in BMD was observed throughout the entire therapy period, with no significant differences in the yearly dynamics of BMD changes observed amongst various polymorphic variants and haplotypes of ER-α.

Conclusions

The EP therapy is effective in the treatment of BMD disorders associated with FHA, and treatment results do not depend on PvuII and XbaI polymorphisms of ER-α.     

Association of IL-27 gene three polymorphisms with Crohn’s disease susceptibility in a Chinese Han population

Objective: To investigate the association of three polymorphisms in the Interleukin-27 (IL-27) gene with CD risk in Chinese population. Methods: This case-control study involved 312 CD patients and 479 age- and sex-matched healthy controls. Genotyping was performed using PCR-LDR method. Data were analyzed using Haplo. Stats program. Results: There were significant differences between patients and controls in allele distributions of rs153109 (P_allele = 0.036). The risk for CD associated with the rs153109-G mutant allele was increased by 26% (95% CI [confidence interval]: 1.02-1.56; P = 0.03) under the additive model and by 45% (95% CI: 1.07-1.97; P = 0.02) under the dominant model. In haplotype analysis, haplotype T-T-G (in order of rs17855750, rs181206 and rs153109) increased the odds of CD by 37% (95% CI: 1.04-1.81; P = 0.028). Conclusions: In conclusion, genetic defects in IL-27 gene showed remarkable associations with CD in Chinese.     

Genetics pathway-based imaging approaches in Chinese Han population with Alzheimer’s disease risk

The tau hypothesis has been raised with regard to the pathophysiology of Alzheimer’s disease (AD). Mild cognitive impairment (MCI) is associated with a high risk for developing AD. However, no study has directly examined the brain topological alterations based on combined effects of tau protein pathway genes in MCI population. Forty-three patients with MCI and 30 healthy controls underwent resting-state functional magnetic resonance imaging (fMRI) in Chinese Han, and a tau protein pathway-based imaging approaches (7 candidate genes: 17 SNPs) were used to investigate changes in the topological organisation of brain activation associated with MCI. Impaired regional activation is related to tau protein pathway genes (5/7 candidate genes) in patients with MCI and likely in topologically convergent and divergent functional alterations patterns associated with genes, and combined effects of tau protein pathway genes disrupt the topological architecture of cortico-cerebellar loops. The associations between the loops and behaviours further suggest that tau protein pathway genes do play a significant role in non-episodic memory impairment. Tau pathway-based imaging approaches might strengthen the credibility in imaging genetic associations and generate pathway frameworks that might provide powerful new insights into the neural mechanisms that underlie MCI.     

Impact of TNF-α and LTα gene polymorphisms on genetic susceptibility in Indian SLE patients

The promoter polymorphisms of tumour necrosis factor-α (TNF-α) and intronic Lymphotoxin-α (LTα) have been implicated as genetic risk factors for systemic lupus erythematosus (SLE) in various ethnic groups. The aim of this study was to investigate an impact of TNF-α (?308G/A; 238G/A) and LTα (+252A/G) gene polymorphisms in disease susceptibility among Indian 200 SLE patients along with 201 healthy controls. The gene polymorphisms were studied by using direct DNA sequencing and Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP) methods. Serum levels were measured by multiplex assay. Allelic frequencies of TNF-α ?308A (OR = 2.3, p = 0.0001, Pc = 0.0003) and LTα +252G (OR = 2.1, p < 0.0001, Pc < 0.001) were significantly higher in SLE patients. Frequency of haplotype-AGG was found to be higher in patients than controls (OR = 12.2, p = 0.0050). Serum levels of TNF-α and LTα also were found to be significantly higher in patients showing variant alleles. TNF-α ?308G/A + A/A genotypes (p < 0.01) and LTα +252 A/G + G/G genotypes (p < 0.02) were significantly associated with renal disorders and haematological manifestations. SLE patients with ?308G/A + A/A genotypes showed higher prevalence of anti-dsDNA antibodies (OR = 3.9, p = 0.0014, Pc = 0.0098) and anti-Sm antibodies (OR = 4.1, p = 0.0002, Pc = 0.0014). The present study suggests TNF-α ?308A and LTα +252G as risk alleles for disease susceptibility associated with higher serum levels of TNF-α and LTα and concomitant discrete clinical features among Indian SLE patients.     

Association of LXRα polymorphisms with obesity and obesity-related phenotypes in an Iranian population

Background: Obesity is a multifactorial disorder due to the complex interaction between genetic and environmental factors. Liver X receptor alpha (LXRα), encoded by the gene NR1H3, is involved in lipoprotein metabolism and its genetic variations may also play a role in the aetiology of obesity.

Aim: To assess the association of two NR1H3 polymorphisms (rs11039155 and rs2279238) and their haplotypes with obesity in an Iranian population.

Subjects and methods: A total of 447 unrelated subjects (including 206 overweight, 162 obese and 79 controls) were enrolled in the study and were genotyped by TaqMan assay using DNA from peripheral blood. The association of these two LXRα polymorphisms with the presence of obesity and overweight was assessed.

Results: There was no significant association between the two SNPs and obesity, even after adjustment for age and sex. By logistic regression using a dominant model, the odds ratios for obesity were: 1.32 (0.85–2.74) for rs11039155 and 0.77 (0.30--1.99) for rs2279238. Haplotype analyses identified three common haplotypes GC, GT and AC with frequency greater than 1%, but none of the haplotypes was associated with the risk of obesity.

Conclusions: This study revealed that there was no significant association between LXRα polymorphisms and the presence of obesity in an Iranian population and suggests that these two SNPs are not major contributors to obesity risk in this population.