Causal effect of serum 25 hydroxyvitamin D concentration on cardioembolic stroke: Evidence from two-sample Mendelian randomization.

BACKGROUND AND AIMS: The putative association between serum 25-hydroxyvitamin D concentration [25(OH)D] and the risk of cardioembolic stroke (CES) has been examined in observational studies, which indicate controversial findings. We performed Mendelian randomization (MR) analysis to determine the causal relationship of serum 25(OH)D with the risk of CES. METHODS AND RESULTS: The summary statistics dataset on the genetic variants related to 25(OH)D was used from the published GWAS of European descent participants in the UK Biobank, including 417,580 subjects, yielding 143 independent loci in 112 1-Mb regions. GWAS summary data of CES was obtained from GIGASTROKE Consortium, which included European individuals (10,804 cases, 1,234,808 controls). Our results unveiled a causal relationship between 25(OH)D and CES using IVW [OR = 0.82, 95% CI: 0.67-0.98, p = 0.037]. Horizontal pleiotropy was not seen [MR-Egger intercept = 0.001; p = 0.792], suggesting an absence of horizontal pleiotropy. Cochrane's Q [Q = 78.71, p-value = 0.924], Rucker's Q [Q = 78.64, p-value = 0.913], and I2 = 0.0% (95% CI: 0.0%, 24.6%) statistic suggested no heterogeneity. This result remained consistent using different MR methods and sensitivity analyses, including Maximum likelihood [OR = 0.82, 95%CI: 0.67-0.98, p-value = 0.036], Constrained maximum likelihood [OR = 0.76, 95%CI: 0.64-0.90, p-value = 0.002], Debiased inverse-variance weighted [OR = 0.82, 95%CI: 0.68-0.99, p-value = 0.002], MR-PRESSO [OR = 0.82, 95%CI 0.77-0.87, p-value = 0.022], RAPS [OR = 0.82, 95%CI 0.67-0.98, p-value = 0.038], MR-Lasso [OR = 0.82, 95%CI 0.68-0.99, p-value = 0.037]. CONCLUSION: Our MR analysis provides suggestive evidence that increased 25(OH)D levels may play a protective role in the development of cardioembolic stroke. Determining the role of 25(OH)D in stroke subtypes has important clinical and public health implications.

Association of baseline and changes in adiponectin, homocysteine, high-sensitivity C-reactive protein, interleukin-6, and interleukin-10 levels and metabolic syndrome incidence: Tehran lipid and glucose study.

Background: Metabolic syndrome (MetS) is accompanied by chronic low-grade inflammation, and inflammatory markers like high-sensitivity C-reactive protein(hs-CRP), interleukin-6(IL-6), and homocysteine(Hcy) contribute to inflammation, obesity, and insulin resistance. Adiponectin(AdipoQ) and interleukin-10(IL-10) are anti-inflammatory markers that play protective roles in MetS. This study aimed to investigate the association between these biochemical marker changes and MetS in a sample of the Tehranian population during six years of follow-up. Methods: In this longitudinal study, 340 adults at baseline and after a six-year follow-up, aged ≥18 years, were selected randomly from the Tehran Lipid and Glucose Study (TLGS). MetS was defined according to the Joint Interim Statement (JIS) criteria. Individuals were categorized into four groups based on their MetS status at baseline and follow-up: 1) non-MetS: participants who did not have MetS at both baseline and follow-up; 2) incident MetS: participants who did not have MetS at baseline but developed MetS during the follow-up ; 3) recovery MetS: participants who had MetS at baseline but no longer had MetS during the follow-up; 4) persistent MetS: participants who had MetS both at baseline and follow-up. Results: The mean follow-up time was 6.1 years. There were 176 subjects in the non-MetS group, 35 in the incident MetS group, 41 in the recovery MetS group, and 88 in the persistent MetS group. Increases in the levels of both hs-CRP 1.40 (95% CI: 1.15, 1.71, p = 0.001) and IL-6 1.09 (95% CI: 1.03, 1.17, p = 0.004) significantly increased the odds of the incident and persistent MetS, respectively. The area under the ROC curve (AUC) was more than 0.69 (p < 0.000) for hs-CRP in predicting MetS incidence and more than 0.86 (p < 0.000) for IL-6 in predicting MetS persistence. Conclusion: After a six-year average follow-up, hs-CRP and IL-6 levels were deemed more reliable predictors of MetS incidence and persistence, respectively.

Identifying new associated pleiotropic SNPs with lipids by simultaneous test of multiple longitudinal traits: An Iranian family-based study.

A number of genome-wide association studies (GWASs) have identified several genetic determinants of plasma lipids in European populations, in which analytical approaches have often been based on the linear regression models and the association test between a SNP and each lipid component individually in cross-sectional designs. Since lipid variations are correlated, the consideration of pleiotropy is necessary and using methods that can perform simultaneous association test of multiple longitudinal traits provides more information about the recognition of the pleiotropic variants. To identify new pleiotropic variants and to determine whether loci identified in previous GWASs can also exert the same effect on lipid concentrations in Iranian population, longitudinal measurements of lipid variations were used in a sample of Iranian population (16,353 individuals within 3100 families) that followed up every 3 years and using a two-step model, the associations of 20,036 available SNPs on chromosome 16 were assessed. Twenty variants within the AC009035.1, SLC12A3, CETP, NLRC5, ESRP2 and, C16orf95 genes showed strong evidence for association with HDL-C, cholesterol, and triglycerides with p-values ranging from 1.7 × 10-102 to 6.6 × 10-5. Since many genetic variants associated with lipids still remain to be determined, the results of the present study may provide valuable information on identifying the associations of new genetic loci with lipid variations in other populations.

Biochemical Assessment: Findings from 20 Years of the Tehran Lipid and Glucose Study.

CONTEXT: The Tehran Lipid and Glucose Study (TLGS) is a community-based study to reveal the frequency of non-communicable diseases (NCDs) in Tehran's population. This research consists of two main parts, a cross-sectional study on the prevalence of cardiovascular risk factors and a 20-year-ongoing prospective cohort study, which was initiated in 1999 in several phases with an approximate duration of 3.6 years, and is still ongoing. The aim of the present study is review the 20 year biochemical findings of the TLGS related to the NCDs in a large sample. METHODS: All articles on biochemical assessments derived from the TLGS from the earliest publications (2002) until 30 January 2018 were reviewed for their findings on different risk factors of NCDs. RESULTS: According to the TLGS findings high sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6), homocysteine (Hcy), age, smoking, hypertension, and obesity were the most important risk factors of cardiovascular diseases (CVD). It was illustrated that in subjects with abdominal obesity, the hs-CRP and IL-6 serum levels were higher than in normal subjects. The most appropriate prognostic indexes and associations were for hs-CRP, IL-6, and Hcy with abdominal obesity, waist circumference, WHtR, and wrist circumference, respectively. Previous studies have demonstrated a direct relationship between obesity and serum levels of inflammatory factors. CONCLUSIONS: According to the results of TLGS, serum levels of biochemical risk factors such as hs-CRP, IL-6, and Hcy could be beneficial in early diagnosis and effective treatment of cardiovascular, obesity and other metabolic diseases.

Cholesteryl ester transfer protein gene variations and macronutrient intakes interaction in relation to metabolic syndrome: Tehran lipid and glucose study.

OBJECTIVES: There are controversial results regarding the effect of the interaction of CETP polymorphisms with dietary fats on the lipid profiles. The aim of this study was to examine the effect of CETP polymorphisms (rs5882 and rs3764261) and macronutrient intakes interaction in relation to metabolic syndrome (MetS) or its components. MATERIALS AND METHODS: In this nested case-control study, subjects were selected from among participants of the Tehran Lipid and Glucose Study. Cases (n=441) were individually matched with two controls (844 non-MetS subjects). DNA samples were genotyped with HumanOmniExpress-24-v1-0 bead chips, including 649,932 SNP loci. RESULTS: The mean ages at baseline were 38.1±10 and 37.0±10 years in women and 36.2±11 and 36.3±11 years in men, respectively in cases and controls. We did not find significant gene-diet interactions between rs5882 and dietary macronutrient intakes in relation to MetS risk. The risk of low HDL-C was lower in the first quartile of MUFA and total fat intake in G allele carriers, compared to AA genotype group. The risk of high BP appeared to increase significantly in higher quartiles of trans-fatty acid intakes (>1.81% of total energy intake) in G allele carriers compared with the AA genotype group. No significant interactions were found between rs3764261 and macronutrient intakes in association with MetS or its components. CONCLUSION: Our findings demonstrate that dietary fats modify the association of rs5882 and risk of low HDL-C and high blood pressure.

Increased Risk of CHD in the Presence of rs7865618 (A allele): Tehran Lipid and Glucose Study.

BACKGROUND: Recent genome-wide association studies (GWAS) in European populations have indicated that the rs12526453 polymorphism located in phosphatase and actin regulator 1 gene (PHACTR1), mapping to chromosome 6p24 and rs7865618 polymorphism in the cyclin-dependent kinase inhibitor B antisense RNA 1 gene (CDKN2B-AS1) on 9p21.3 are associated with coronary heart disease (CHD). This study was carried out to investigate the association of these polymorphisms and CHD in an Iranian population. METHODS: In the present case-control study, 420 patients with CHD events were recruited from the population of the Tehran lipid and glucose study (TLGS); 407 healthy controls matched for age and sex were selected from the same population. The SNPs rs12526453 and rs7865618 were genotyped using amplification refractory mutation system-polymerase chain reaction (ARMS-PCR). RESULTS: The allele frequency of both SNPs deviated from Hardy-Weinberg equilibrium. The C allele frequency of the rs12526453 (68.5%, P = 0.11) and A allele of the rs7865618 (68.8%, P = 0.09) were the most prevalent alleles in both the case and control groups. The results indicated a significant association between the presence of risk alleles of rs7865618 and CHD in the TLGS population (P = 0.03; OR: 1.73; CI95%: 1.04 - 2.88). CONCLUSION: Due to the importance of chromosome 9p21 region and its relation with cardiovascular disease, the allelic pattern of its variation should be studied in different populations. The relation between this polymorphism and cardiovascular disease in the studied population confirms the importance of this region.

Maternal Characteristics and Incidence of Overweight/Obesity in Children: A 13-Year Follow-up Study in an Eastern Mediterranean Population.

Objectives To investigate clustering of parental sociobehavioral factors and their relationship with the incidence of overweight and obesity in Iranian children. Methods Demographics, body weight, and certain medical characteristics of the parents of 2999 children were used to categorize parents by cluster; children's weights were assessed for each cluster. Specifically, survival analysis and Cox regression models were used to test the effect of parental clustering on the incidence of childhood overweight and obesity. Results Maternal metabolic syndrome, education level, age, body weight status, and paternal age had important roles in distinguishing clusters with low, moderate, and high risk. Crude incidence rates (per 10,000 person-years) of overweight and obesity were 416.8 (95% confidence interval (CI) 388.2-447.5) and 114.7 (95% CI 101.2-129.9), respectively. Children of parents with certain constellations of demographic and medical characteristics were 37.0 and 41.0% more likely to become overweight and obese, respectively. Conclusions for Practice The current study demonstrated the vital role of maternal characteristics in distinguishing familial clusters, which could be used to predict the incidence of overweight and obesity in children.

Identification of Sequence Variation in the Apolipoprotein A2 Gene and Their Relationship with Serum High-Density Lipoprotein Cholesterol Levels.

BACKGROUND: Apolipoprotein A2 (APOA2) is the second major apolipoprotein of the high-density lipoprotein cholesterol (HDL-C). The study aim was to identify APOA2 gene variation in individuals within two extreme tails of HDL-C levels and its relationship with HDL-C level. METHODS: This cross-sectional survey was conducted on participants from Tehran Glucose and Lipid Study (TLGS) at Research Institute for Endocrine Sciences, Tehran, Iran from April 2012 to February 2013. In total, 79 individuals with extreme low HDL-C levels (≤5th percentile for age and gender) and 63 individuals with extreme high HDL-C levels (≥95th percentile for age and gender) were selected. Variants were identified using DNA amplification and direct sequencing. RESULTS: Screen of all exons and the core promoter region of APOA2 gene identified nine single nucleotide substitutions and one microsatellite; five of which were known and four were new variants. Of these nine variants, two were common tag single nucleotide polymorphisms (SNPs) and seven were rare SNPs. Both exonic substitutions were missense mutations and caused an amino acid change. There was a significant association between the new missense mutation (variant Chr.1:16119226, Ala98Pro) and HDL-C level. CONCLUSION: None of two common tag SNPs of rs6413453 and rs5082 contributes to the HDL-C trait in Iranian population, but a new missense mutation in APOA2 in our population has a significant association with HDL-C.

Ischemic postconditioning provides cardioprotective and antiapoptotic effects against ischemia-reperfusion injury through iNOS inhibition in hyperthyroid rats.

Ischemic postconditioning (IPost) is a strategy to provide protection against ischemia-reperfusion (IR) injury. The cardioprotective effects of IPost in cases of ischemic heart disease along with co-morbidities like hyperthyroidism remain unknown. The aim of this study was to investigate the effects of IPost on expression of eNOS, iNOS, Bax, and Bcl-2 genes in hyperthyroid male rats, subjected to myocardial IR. Hyperthyroidism was induced by adding thyroxine to drinking water for a period of 21 days. Using the Langendorff device hearts were perfused, then subjected to a 30-minute global ischemia which was followed by 120 min of reperfusion; subsequently IPost was induced immediately after ischemia. Results indicated that following IR, expression of eNOS and Bcl-2 decreased, whereas expression of iNOS and Bax increased in both the control and hyperthyroid groups. In hyperthyroid animals, IPost significantly increased expression of eNOS by 3.19 fold and Bcl-2 by 3.66 fold; it also decreased expression of Bax by 51%, and reduced IR-induced DNA laddering pattern and infarct size (45.7 ± 1.82% vs. 59.3 ± 1.83%, p<0.05) in the presence of aminoguanidine (AG), a selective iNOS inhibitor. In conclusion, IPost per se could not provide cardioprotection against myocardial ischemia in hyperthyroid rats, a loss of which however was restored by the combination of IPost and iNOS inhibition that acts by a decrease in Bax and an increase in both eNOS and Bcl-2 expression.

Association of Lecithin Cholesterol Acyltransferase rs5923 Polymorphism in Iranian Individuals with Extremely Low High-Density Lipoprotein Cholesterol: Tehran Lipid and Glucose Study.

BACKGROUND: The serum concentration of high-density lipoprotein cholesterol (HDL-C) is one of the important heritable risk factors for cardiovascular disease and is a target for therapeutic intervention. In this study, we aimed to evaluate the effects of lecithin cholesterol acyltransferase (LCAT) gene polymorphism rs5923 on LCAT enzyme activity and serum HDL-C concentration. METHODS: The study population was selected from consecutive individuals with HDL-C ≤ 5th percentile (n = 73) and extremely high HDL-C ≥ 95th percentile (n = 57) who had participated in the Tehran Lipid and Glucose Study. The rs5923 polymorphism was genotyped using direct sequencing. LCAT activity was measured by fluorometric assay kit, and lipid concentrations were measured using the enzymatic colorimetric method. RESULTS: The genotype frequencies were significantly different between the high HDL-C group (CC 94.7%, CT 5.3%) and the low HDL-C group (CC 83.6%, CT 16.4%) (P = 0.048). The T-allele frequencies in subjects with low and high HDL-C were 0.082 and 0.026, respectively (P = 0.16). The association of the single-nucleotide polymorphism rs5923 with low HDL-C was not statistically significant after adjustment for age, sex, and BMI (odd ratio = 2.65, 95% confidence interval = 0.32-21.5, P = 0.36, regression logistic analysis). Also, the effects of LCAT enzyme activity did not depend on the HDL-C level (P = 0.24). CONCLUSION: rs5923 polymorphism is not associated with low HDL-C levels in Iranian population.

The association between inflammatory markers and obesity-related factors in Tehranian adults: Tehran lipid and glucose study.

OBJECTIVES: Obesity considered being a low-grade inflammatory disease. The objective of this study was to examine the association between inflammatory markers (IM) including C-reactive protein (hs-CRP), Interleukin-6 (IL-6), and homocystein (Hcy) and obesity-related factors (e.g. BMI, waist, hip) in adult participants of Tehran lipid and glucose study (TLGS). MATERIALS AND METHODS: In this cross-sectional study, 352 individuals (132 men and 220 women), age ≥19 years, were randomly recruited from participants of TLGS population. The serum levels of hs-CRP, IL-6, Hcy were determined using the enzyme linked immunosorbent assay (ELISA) method. Variables were compared by sample t-test. Bivariate linear correlation was estimated using Pearson's correlation coefficient. Linear regression analysis was applied to investigate the association between IMs and anthropometric and biochemical variables. RESULTS: The mean age of participants was 46.1±16.1 years. abdominal obesity was present in 199(56.5%) individuals. levels of hs-CRP and IL-6 increased in the abdominally obese group (1507±3.3 vs. 577.8±4.3 ng/ml P<0.001) (3.6±3.3 vs. 1.9±3.8 pg/ml P< 0.001), and in the same group, the best predictors for hs-CRP, IL-6 and Hcy were waist (WC), waist to height ratio (WHtR) and wrist respectively; hip and WHtR were the best predictors for Hcy and hs-CRP in the normal group. A linear augmentation in hs-CRP and IL-6 levels was observed in association with obesity categorizes. CONCLUSION: This study provides evidence that abdominally obese individuals had higher levels of IMs. Wrist, waist and WHtR were the best predictors for Hcy, hs-CRP and IL-6 respectively in this group.

Recurrence risk ratio of siblings and familial aggregation of the metabolic syndrome among Tehranian population.

BACKGROUND: In this study, we aimed to determine the extent of possible genetic influence on cardio-metabolic risk factors, evaluate the familial aggregation of MetS and estimate the siblings' recurrence risk ratios in a Tehrani population. METHODS: In a cross-sectional observational study, we made anthropometric, blood pressure, and biochemical measurements in each member of 566 Tehrani nuclear families. RESULTS: Grandmothers had the highest incidence of atherosclerotic risk factors. Four factors were found which accounted for 77.7% of the overall variance. Recurrence risk ratio among siblings was 5.61 (95% confidence interval [CI]: 3.15-9.97). The adjusted odds ratio (OR) of proband's MetS status was 1.33 (95% CI: 1.06-1.67). The adjusted OR for the four factors to predict MetS were all significant, with obesity having the highest risk (OR: 7.50, CI: 5.91-9.52), followed by dyslipidemia/hyperglycemia (OR: 4.86, CI: 4.03-5.87), and blood pressure (OR: 4.20, CI: 3.51-5.02). CONCLUSION: A high risk of MetS (five-fold) was found in siblings with MetS proband. Moreover, findings confirm the importance of obesity for the aggregation of MetS by nearly seven-fold in the study population.

Identification of genetic variants of lecithin cholesterol acyltransferase in individuals with high HDL­C levels.

Among the most common lipid abnormalities, a low level of high-density lipoprotein-cholesterol (HDL­C) is one of the first risk factors identified for coronary heart disease. Lecithin cholesterol acyltransferase (LCAT) has a pivotal role in the formation and maturation of HDL-C and in reverse cholesterol transport. To identify genetic loci associated with low HDL-C in a population-based cohort in Tehran, the promoter, coding regions and exon/intron boundaries of LCAT were amplified and sequenced in consecutive individuals (n=150) who had extremely low or high HDL-C levels but no other major lipid abnormalities. A total of 14 single-nucleotide polymorphisms (SNPs) were identified, of which 10 were found to be novel; the L393L, S232T and 16:67977696 C>A polymorphisms have been previously reported in the SNP Database (as rs5923, rs4986970 and rs11860115, respectively) and the non-synonymous R47M mutation has been reported in the Catalogue of Somatic Mutations in Cancer (COSM972635). Three of the SNPs identified in the present study (position 6,531 in exon 5, position 6,696 in exon 5 and position 5,151 in exon 1) led to an amino acid substitution. The most common variants were L393L (4886C/T) in exon 6 and Q177E, a novel mutation, in exon 5, and the prevalence of the heterozygous genotype of these two SNPs was significantly higher in the low HDL-C groups. Univariate conditional logistic regression odds ratios (ORs) were nominally significant for Q177E (OR, 5.64; P=0.02; 95% confidence interval, 1.2­26.2). However, this finding was attenuated following adjustment for confounders. Further studies using a larger sample size may enhance the determination of the role of these SNPs.

The age effect on the association between the scavenger receptor class B type I (SR-BI) polymorphism and HDL-C level: Tehran Lipid and Glucose Study.

INTRODUCTION: The scavenger receptor class B type I (SR-BI) is a key component in the reverse cholesterol transportation. The aim of this study was to assess the association between exon1 (G → A) polymorphism of SR-BI gene and lipid profiles among the Tehran Lipid and Glucose Study (TLGS) population. MATERIALS AND METHODS: This cross-sectional study included 774 adults (322 males and 452 females) aged 20-70 years who were randomly selected from among TLGS population. Anthropometrical and biochemical variables for participants were measured. Selected SR-BI gene polymorphism was determined with restriction fragment length polymorphism, via Alu restriction enzyme. RESULTS: Minor allele frequency for SR-BI polymorphism in the selected population was 0.159. Allele frequencies were in conformity with Hardy-Weinberg equilibrium. Association between (G → A) SR-BI polymorphism and high density lipoprotein cholesterol (HDL-C) and HDL3 was significant only after adjustment for age as a potential covariate (p = 0.046, 0.041, respectively); however, the results did not improve after adjustment for sex. DISCUSSION: The result of this study confirms the role of age as a potential confounder which could modify the association between the SR-BI single nucleotide polymorphism and HDL-C level.

Genetic polymorphisms in the APOA1 gene and their relationship with serum HDL cholesterol levels.

Low high density lipoprotein cholesterol (HDL-C) is a known risk factor of coronary artery disease. Apolipoprotein A1 (APOA1) is the most abundant component of HDL-C. This study aimed at identifying sequence variations (rare and common) in the APOA1 gene and its association with serum HDL-C levels. This study was conducted from April 2012 to February 2013 on 79 Tehranians (participants of Tehran Lipid and Glucose Study) with extremely low HDL-C (within the 5th percentile) and 63 individuals with extremely high HDL-C (within the 95th percentile) levels. After DNA amplification by PCR, DNA sequencing of all three exons and 700 bps of promoter region of the APOA1 gene was performed. Sequence results were analyzed and interpreted using the appropriate software and variants were identified. After sequencing 42 common and rare variants were identified, 11 of which were known variants and the others had been unreported so far. Of the exonic variants, 11 were missense, 6 were synonymous and 1 was nonsense. There was a significant association between serum HDL-C and variant of rs2070665 as well as variants Chr.11:116707788, Chr.11:116708059, Chr.11:116708036, Chr.11:116707729, rs201148448, Chr.11:116707018, Chr.11:116707801, Chr.11:116708530, Chr.11:116708088, rs121912724 and Chr.11:116706966 (p < 0.001). Variants Chr.11:116707018, rs121912724 and 2070665 were independent predictors of the HDL-C level (p < 0.001). SNP Chr.11:116707018 was the strongest predictor of the HDL-C level (OR 7.527, p < 0.001). This study identified 42 variants in APOA1 gene, 31 of which were new variants. Three variants of rs2070665, rs121912724 and Chr.11:116707018 could predict the HDL-C level independently. Variant rs2070665 was protective against low-HDL-C levels while variants rs121912724 and Chr.11:116707018 were risk factors for that in our population.

Genetic polymorphism of vitamin D receptor gene affects the phenotype of PCOS.

AIMS: Polycystic ovary syndrome (PCOS), a common female endocrine disorder, represents a wide range of clinical manifestations and disease severity. Recent studies suggest an association between gene variants involved in vitamin D metabolism and common metabolic disturbances in PCOS. We aimed to examine the association of vitamin D receptor (VDR) gene variant with PCOS susceptibility and the severity of disease phenotype. METHODS: All participants, including 260 PCOS women (cases) and 221 normoovulatory women (controls), were recruited from a reproductive endocrinology clinic. Cases were divided into the severe and mild PCOS phenotype groups, based on their clinical and paraclinical features. An adenosine to guanine single nucleotide polymorphism of VDR gene (rs757343) was genotyped using the PCR-RFLP method. RESULTS: Distributions of genotypes and alleles did not differ between cases and controls, indicating that this SNP is not associated with increased risk for PCOS. However, this SNP was found to be associated with the severity of the PCOS phenotype. In particular, presence of the A allele is associated with a 74% increased risk of severe phenotype development (OR, 1.74; 95% CI, 1.07-2.82). CONCLUSION: The genetic variant of the VDR was found to have an association with severity of clinical features of PCOS, but none with disease risk.

Logic regression analysis of association of gene polymorphisms with low HDL: Tehran Lipid and Glucose Study.

INTRODUCTION: Logic regression is a generalized regression method that can recognize complex Boolean interactions of binary variables. It has been successfully applied to single-nucleotide polymorphism (SNP) data because of the importance of interactions in SNP association studies. The objective of this study is to assess the association between high-density lipoprotein (HDL) function and some related gene polymorphisms after adjusting for potential confounders using logic regression. METHODS: Subjects in this cross-sectional study were randomly selected from among participants of the Tehran Lipid and Glucose Study (TLGS). A total of 436 subjects (172 men and 264 women), aged ≥20 years, were selected to be included in the current study. Logic regression analysis was used in order to recognize the combination of genetic main effects and possible interactions associated with HDL-C level. Cross validation and randomization test were carried out to avoid over fitting of the models. RESULTS: The cross validation test suggested three Boolean combinations with four predictors for a fully-adjusted logic model. The fully adjusted model showed that those who carry an Apo E gene E3 allele or have high TG level have an odds ratio of 2.35 (95% CI:1.3-4.25) for having low HDL compared to other subjects. In addition, subjects with high TG level have an odds ratio of 2.73 (95% CI: 1.65, 4.53) for having low HDL. CONCLUSION: The results showed that logic regression is a powerful method to find the interaction between high TG level and Apo E polymorphism associated with low HDL.

The relationship between metabolic syndrome, cardiometabolic risk factors and inflammatory markers in a Tehranian population: the Tehran Lipid and Glucose Study.

OBJECTIVE: The aim of this study was to investigate the relationship between the high sensitivity C-reactive protein (hsCRP), interleukin-6 (IL-6) and homocysteine (Hcy) levels and cardiometabolic risk factors in subjects with and without metabolic syndrome (MetS) in a sample of the Tehranian population. METHODS: In this cross-sectional study, 365 individuals aged ≥ 19 years were randomly selected from among participants of the Tehran Lipid and Glucose Study (TLGS). The serum levels of IL-6, hsCRP and Hcy were determined using the Enzyme Linked Immunosorbent Assay (ELISA) method. RESULTS: Of the 365 subjects, aged a mean of 46.1 ± 16.1 years, MetS was present in 160 (43.8%) individuals. The levels of hsCRP, Hcy and IL-6 were higher in the subjects with MetS. A gradual and significant increase in the levels of hsCRP was found in association with increasing numbers of MetS components after adjusting for sex and age. A strong linear augmentation in the hsCRP levels was observed as the numbers of MetS components increased. Additionally, an increase of 0.40 was observed in the hsCRP levels in association with increases in each component of MetS adjusted for age and sex. The best predictors for the levels of hsCRP, IL-6 and Hcy in the subjects with MetS were hip, waist to height ratio (WHtR) and height, respectively. CONCLUSION: Hip and WHtR are significant predictors of elevated levels of hsCRP and IL-6 associated with MetS, respectively.

Association between TPO gene polymorphisms and Anti-TPO level in Tehranian population: TLGS.

INTRODUCTION: Thyroid peroxidase (TPO) gene variations are one cause of thyroid autoimmune diseases. The aim of this study was to examine the association between the T1936C, T2229C and A2257C polymorphisms of the TPO gene and Anti-TPO level. MATERIALS AND METHODS: In this case-control study, 188 individuals (86 males and 102 females), aged 20-80 years, were randomly selected from among the Tehran Lipid and Glucose Study (TLGS) population. A2257C and T2229C SNPs were detected with RFLP by use of BsrI and Eco57I as the restriction enzymes respectively, while the T1936C SNP was determined with ARMS-PCR. RESULTS: In the presence of the C allele of T1936C, Anti-TPO level was significantly increased (CC: 238±43.3, CT: 47.7±15.9, TT: 74.1±11.3 IU/L p=0.002); however, this association was attenuated after adjustment for sex and age (p=0.059). No significant difference, before and after adjustment, was found in Anti-TPO level in the presence of T2229C SNP (CC: 129.1±24.5, CT: 43.5±12.6, TT: 126.5±13.8 IU/L p=0.196). The association between A2257C and Anti-TPO level was only significant after adjustment for potential confounders (p=0.007). The association between ATC and CTT haplotypes and Anti-TPO level was significant (p=0.023, 0.021 respectively), the association between CTT and Anti-TPO concentration was also significant after adjustment for sex (p=0.014). CONCLUSION: The results of the present study confirmed the association between TPO gene polymorphisms and Anti-TPO level in the Tehranian population.

Haplotype frequency distribution for 7 microsatellites in chromosome 8 and 11 in relation to the metabolic syndrome in four ethnic groups: Tehran Lipid and Glucose Study.

INTRODUCTION: Different variants of haplotype frequencies may lead to various frequencies of the same variants in individuals with drug resistance and disease susceptibility at the population level. MATERIALS AND METHODS: In this study, the haplotype frequencies of 4 STR loci including the D8S1132, D8S1779, D8S514 and D8S1743, and 3 STR loci including D11S1304, D11S1998 and D11S934 were investigated in 563 individuals of four Iranian ethnic groups in the capital city of Iran, Tehran. One hundred thirty subjects had the metabolic syndrome. Haplotype frequencies of all markers were calculated. RESULTS: There were significant differences in the haplotype frequencies in short and long alleles between the metabolic affected subjects and controls. In addition, haplotype frequencies were significant in the four ethnic groups in both chromosomes 8 and 11. CONCLUSION: Our findings show a relation between the short allele of D8S1743 in all related haplotype frequencies of subjects with metabolic syndrome. These findings may require more studies of some candidate genes, including the lipoprotein lipase gene, in this chromosomal region.