ABCA1 single nucleotide polymorphisms on high-density lipoprotein-cholesterol and overweight: the D.E.S.I.R. study

The adenosine triphosphate-binding cassette A1 (ABCA1) gene plays a key role in reverse cholesterol transport. Some ABCA1 gene polymorphisms have been associated with high-density lipoprotein-cholesterol (HDL-C) concentrations. The aim of this study was to assess the effect of three polymorphisms, C69T, G378C, and G1051A (R219K), on HDL-C levels and their interaction with BMI in more than 5000 French whites from the D.E.S.I.R. (Data from an Epidemiological Study on the Insulin Resistance syndrome) cohort study. The T allele of the C69T single nucleotide polymorphism (SNP) was associated with higher HDL-C levels in normal-weight men (BMI <25 kg/m(2)). The C allele of the G378C SNP was associated with lower HDL-C in overweight subjects (BMI > or =25 kg/m(2)). For the G1051A SNP, in the normal-weight group, the minor A allele was significantly associated with higher HDL-C levels. In contrast, in overweight people, the minor allele was associated with lower HDL-C levels. After accounting for multiple testing, empiric p values remained significant for the associations between G378C SNP and HDL-C in the overweight group and between G1051A SNP and HDL-C in the normal-weight group. This study suggests that ABCA1 gene polymorphisms modulate HDL-C concentrations, in interaction with BMI, and, thus, they might influence cardiovascular risk in the general population.     

P2Y12 receptor gene polymorphisms are associated with epilepsy

The basic research indicated that microglial P2Y12 receptors (P2Y12Rs) are involved in the pathophysiology of epilepsy through regulated microglial-neuronal interactions, aberrant neurogenesis, or immature neuronal projections. However, whether the clinic case of epilepsy would be associated with P2Y12 receptor gene polymorphisms is presented with few data. In our study, a total of 176 patients with epilepsy and 50 healthy controls were enrolled. Two single-nucleotide polymorphisms, namely rs1491974 and rs6798347, were selected for analysis. The results revealed that carriers of the G allele of rs1491974 G>A or rs6798347 G>A may be associated with an increased risk of epilepsy (OR = 0.576, 95% CI = 0.368–0.901, p = 0.015; OR = 0.603, 95% CI = 0.367–0.988, p = 0.043). Interestingly, we found that the rs1491974 G>A genotype and allele frequencies have only a significant difference in female instead of male case (p = 0.004 for genotype; p = 0.001 for allele). The subgroup analysis demonstrated that individuals with the rs1491974 G>A genotype might have more frequent seizure (OR = 0.476, 95% CI = 0.255–0.890; p = 0.019). These data implied that both rs1491974 and rs6798347 polymorphisms of P2Y12R would be able to play import roles in epilepsy susceptibility, whereas the rs1491974 polymorphism may be specifically related to seizure frequency.     

ESR1 polymorphism is associated with plasma lipid and apolipoprotein levels in Caucasians of the Rochester Family Heart Study

We evaluated six estrogen receptor 1 (ESR1) polymorphisms for association with ten plasma lipid and apolipoprotein traits in 1,847 individuals (941 females and 906 males) in the multi-generation Rochester Family Heart Study using a generalized estimating equation approach. Apolipoprotein A-I (apoA-I), apoA-II, and HDL-cholesterol (HDL-C) were associated with exon 4 rs1801132 (Pro325Pro) genotype (P = 0.0044, P = 0.0048, and P = 0.0035, respectively). Positive correlation between levels of apoA-I, apoA-II, and HDL-C and the number of G alleles was observed in females (P = 0.0120, P = 0.0032, and P = 0.0030), but not males (P > 0.05). Because few studies have evaluated the effect of ESR1 gene polymorphisms on lipid traits in children, we also stratified our sample at the age of 15 years. There was evidence of association between intron 1 single-nucleotide polymorphisms rs9322331 and rs9340799 and apoC-II, and triglycerides (TGs) in youths 15 years and younger. In youths, evidence of association between rs9322331 and rs9340799 and apoC-II was stronger in males (P = 0.0036 and P = 0.0124) than in females (P > 0.05), whereas evidence of association with TG was stronger in females (P = 0.0030 and P = 0.0024) than in males (P > 0.05). These findings suggest that ESR1 variation plays an age- and sex-dependent role in determining plasma lipid and apolipoprotein levels.     

Association of Hepatocyte Nuclear Factor 4 Alpha Polymorphisms with Type 2 Diabetes With or Without Metabolic Syndrome in Malaysia

This study investigated the association of hepatocyte nuclear factor 4 (HNF4) alpha single nucleotide polymorphisms (SNPs) with type 2 diabetes with or without metabolic syndrome in Malaysia. Nine HNF4 alpha SNPs were genotyped in 390 type 2 diabetic subjects with metabolic syndrome, 135 type 2 diabetic subjects without metabolic syndrome, and 160 control subjects. The SNPs rs4810424, rs1884613, and rs2144908 were associated with protection against type 2 diabetes without metabolic syndrome (recessive P = 0.018, OR 0.32; P = 0.004, OR 0.25; P = 0.005, OR 0.24, respectively). The 6-SNP haplotype2 CCCGTC containing the risk genotype of these SNPs was associated with higher risk for type 2 diabetes with or without metabolic syndrome (P = 0.002, OR 2.2; P = 0.004, OR 3.1). These data suggest that HNF4 alpha SNPs and haplotypes contributed to increased type 2 diabetes risk in the Malaysian population.     

Two genetic variants in FABP1 and susceptibility to non-alcohol fatty liver disease in a Chinese population

Liver fatty acid-binding protein (FABP1) serves as a key regulator of hepatic lipid metabolism, and polymorphisms within the FABP1 gene have been associated with several metabolic traits. To investigate the association between FABP1 polymorphisms and the risk of non-alcohol fatty liver disease (NAFLD) in a Chinese population, the genotypes and haplotypes of FABP1 (rs2241883 T/C and rs1545224G/A) were determined in 553 patients with NAFLD and 553 healthy controls. The results showed that individuals with at least one copy of the rs2241883 C allele (TC or CC genotype) had an elevated risk for developing NAFLD (odds ratio [OR]=1.32, 95% CI: 1.01-1.71), and individuals with at least one copy of the rs1545224 A allele (GA or AA genotype) also had a significantly increased risk for NAFLD (OR=1.52, 95% CI: 1.14-2.02). Cumulative effect analysis of the two SNPs revealed that individuals with two risk genotypes were at significantly higher risk of NAFLD than those without risk genotype, and a significant trend of increased risk with increasing numbers of risk genotype was observed. Stratification analysis showed that the rs2241883 C allele carriers had higher level of LDL-C and the rs1545224 A allele carriers had higher level of FPG than those without this allele. In addition, haplotype analysis revealed that the one composed of the rs1545224 A and rs2241883 C variants was significantly associated with an increased risk for NAFLD (OR=1.34; 95% CI=1.05-1.40) compared to the GT haplotype. Taken together, the present study suggests that genetic variations within FABP1 influence susceptibility to NAFLD independently or jointly.     

A polymorphism at the IL6ST (gp130) locus is associated with traits of the metabolic syndrome

The interleukin 6 signal transducer (IL6ST, also known as gp130) is a ubiquitously expressed intermediate of the interleukin-6 signaling pathway. We investigated whether genetic variability at the IL6ST locus is involved in the modulation of metabolic traits and the etiology of the metabolic syndrome (MS). Four haplotype-tagging single nucleotide polymorphisms were typed in two populations of non-diabetic subjects, one from Northern Italy (Padua (PD), n = 630), the other from Southern Italy (San Giovanni Rotondo (SGR), n = 553). In the PD population, a nominally significant association was observed between fasting glucose and rs715180 (P = 0.02), rs3729960 (P = 0.02), and rs10940495 (P = 0.05), between homeostasis model assessment index (HOMA(IR)) and rs715180 (P = 0.04), and between triglycerides and rs3729960 (P = 0.03). In the SGR population, high-density lipoprotein (HDL) levels were associated with rs715180 (P = 0.01), systolic blood pressure and waist circumference with rs3729960 (P = 0.005 and 0.02, respectively). The frequency of rs715180 minor allele carriers progressively decreased from individuals with no MS components to those with three or more components (P for trend = 0.006 in the two populations combined). Compared to major allele homozygotes, minor allele carriers had 40% lower odds of having at least one MS component (Odds ratio = 0.6, 95% confidence interval 0.4-0.8, P = 0.005). These findings point to IL6ST variants as possible determinants of impaired glucose metabolism and other abnormalities of MS.     

Relationship of high density lipoprotein cholesterol to cholesterol metabolism in the baboon (Papio sp.)

Genetic effects on serum high density lipoprotein (HDL) cholesterol concentration and several parameters of a two-pool model of cholesterol metabolism were investigated in 79 baboons, the progeny of 6 sires. Significant differences (P less than 0.05) were observed among the sire progeny groups for HDL cholesterol (HDL-C), cholesterol production rate, cholesterol mass of pool A, and the rate constants KA and KAB. Rank correlations (rs) revealed that the sire progeny group means for HDL-C are closely correlated with those for the cholesterol mass of pool A (rs = 0.89), KA (rs = -0.78), and KAB (rs = -0.94). These strong correlations suggest that pool A, KA, and KAB are influenced to a large degree by the same genes that regulate HDL-C concentration. The strong inverse relationship (rs = -0.78) between HDL-C and KA suggests that the differences among these sire progeny groups for HDL-C are due chiefly to those metabolic processes which regulate cholesterol excretion from pool A. This conclusion is consistent with reports that HDL-C is a preferred precursor for bile acid synthesis.     

Association of rs11801299 and rs1380576 polymorphisms at MDM4 with risk,clinicopathological features and prognosis in patients with retinoblastoma

Backgroundrs11801299 and rs1380576, two novel polymorphisms in MDM4 gene, have been investigated in several different cancer types. However, the role of these two polymorphisms in retinoblastoma (RB) remains unclear.MethodsA total of 126 patients with primary RB and 148 age-/gender-matched controls were included in this retrospective study. The frequency of rs11801299 and rs1380576 were determined between RB patients and controls. The association of these two polymorphisms with clinicopathological characteristics, prognosis were further evaluated.ResultsAA genotype at rs11801299 was significantly associated with an increased risk of developing RB (OR = 2.06, 95%CI 1.09–3.90). The possibility of developing RB was also significantly increased in individuals with A allele at rs11801299 (OR = 1.49, 95%CI 1.06–2.08). RB patients carrying AA genotype and A allele at rs11801299 were more likely to have tumor invasion and poor differentiation. As for rs1380576, a significantly lower risk of developing RB was observed in patients with G allele (CG + GG) compared with wild-type CC genotype (OR = 0.59, 95%CI 0.36–3.95). RB patients with GG genotype or G allele had a lower risk of developing highly aggressive cancer. Kaplan-Meier curves and log-rank results revealed that RB patients carrying AA genotype or A allele (AA + GA) at rs11801299 had significantly poorer prognosis. Multivariate COX analysis showed that the rs11801299 G allele was associated with decreased survival but was not an independent prognostic factor.Conclusionrs11801299 was significantly associated with RB risk, pathological differentiation, tumor aggressiveness and poor prognosis.     

Influence of b2 adrenergic receptor polymorphism (rs1042713 and rs1042714) on anthropometric,hormonal and lipid profiles in polycystic ovarian syndrome

BackgroundPolycystic ovarian syndrome (PCOS) is a frequently encountered disorder. This study aimed to identify polymorphisms in ADRB2 in Saudi PCOS development and to study its influence on lipids, hormones, and anthropometric parameters.MethodsSaudi females (100) suffering from PCOS and healthy controls (100) were investigated. The estimation of cholesterol, triglycerides, high-density lipoprotein (HDL-C), low-density lipoprotein (LDL-C), plasma glucose, leptin Insulin, and ghrelin were carried out. The DNA was extracted, and ADRB2 fragment carrying the exon 1 was amplified and sequenced.ResultsThe waist, W/H ratio, lipids, glucose, and insulin were significantly higher in the obese PCOS compared to the normal weight group. The leptin and ghrelin were not different. Two single nucleotide polymorphisms (SNPs): rs1042713 (Arg16Gly; A>G) and rs1042714 (Gln27Glu; C>G) were identified. The genotype and allele frequency of rs1042713 did not differ in the total PCOS and normal weight, and obese PCOS compare to the controls. However, rs1042714 was significantly associated with PCOS development, where the minor G allele was protective against PCOS development.ConclusionsThe rs1042714 polymorphism of the ADRB associates with PCOS development in Saudis, while rs1042713 does not. However, the GG genotype of rs1042713 associates significantly with elevated BMI, waist, hip, W/H, and leptin, and decreased ghrelin. On the other hand, rs1042714 genotypes do not associate with any abnormality except the homozygous GG have higher triglycerides and lower HDL-C. Interestingly, glucose showed different correlation patterns in individuals carrying different genotypes of the two studied SNP, indicating clearly that the metabolic responses to a normal nutrient are significantly influenced by the genotypes of the SNPs in ADRB2.     

The effect of ponderal index at birth on the relationships between common LEP and LEPR polymorphisms and adiposity in adolescents

This study examined the effect of ponderal index (PI) at birth on the relationships between eight common polymorphisms of the leptin (LEP) and leptin receptor (LEPR) genes and adiposity in adolescents. A total of 823 European adolescents (45.4% girls) aged 14.8 ± 1.4 years were genotyped for the LEP (rs2167270, rs12706832, rs10244329, rs2071045, and rs3828942) and LEPR (rs1137100, rs1137101, and rs8179183) polymorphisms. The PI was calculated from parental reports of birth weight and length. Fat mass index (FMI) was calculated. Analyses were adjusted for relevant confounders. An "adiposity-risk-allele score" based on genotypes at the three single-nucleotide polymorphisms (SNPs) associated with adolescents' FMI in adolescents within the lower tertile of PI was calculated. The LEP rs10244329 and rs3828942 polymorphisms were associated with higher FMI only in adolescents within the lower PI tertile (+0.55 kg/m(2) per minor T allele, P = 0.040, and +0.58 kg/m(2) per major G allele, P = 0.028, respectively). The LEPR rs8179183 polymorphism was significantly associated with higher FMI in adolescents within the lower PI tertile (+0.87 kg/m(2) per minor C allele, P = 0.006). After correction for multiple comparisons, only the association between the LEPR rs8179183 and FMI persisted. However, each additional risk allele conferred 0.53 kg/m(2) greater FMI in adolescents within the lower tertile of PI (P = 0.008). In conclusion, our results suggest that those adolescents born with lower PI could be more vulnerable to the influence of the LEP rs10244329 and rs3828942 polymorphisms and LEPR rs8179183 polymorphism on total adiposity content. Due to the relatively small sample size, these findings should be replicated in further larger population samples.     

The Association Between <Emphasis Type="Italic">APOA5</Emphasis> Gene Polymorphisms and Plasma Lipids in the Turkish Cypriot Population: A Possible Biomarker for Preventing Cardiovascular Diseases

Apolipoprotein A5 (APOA5 or APO A-V) polymorphisms have long been reported to be associated with cardiovascular disease and plasma lipid levels. The present study was undertaken to investigate the relationship between the rs662799, rs3135507, and rs2075291 with biochemical parameters in the Turkish Cypriot population. A total of 100 Turkish Cypriot volunteer subjects (53 female and 47 male), with a mean age of 40.8, participated in the study. A basic biochemical analysis, including serum glucose, total serum cholesterol, HDL-C, LDL-C, and triglycerides, was performed for each participant. Genotyping for the APOA5 three polymorphisms was performed by polymerase chain reaction followed by restriction fragment length polymorphism analysis. Biochemical parameters except the low-density lipoprotein cholesterol (LDL-C) were all within the normal limits. LDL-C was found to be slightly elevated in participants according to WHO guidelines. With respect to the genotype and allele distributions of APOA5 rs662799 T>C polymorphism, TT genotypes are more frequent (62%) in the population and the frequency of T allele is 0.78. The TT genotype for APOA5 rs2075291 G<T was not observed in the study population. Ancestral GG is the only genotype present in the study population. Minor Allele Frequency of APOA5 rs3135507 G>A variant is 0.12 for the A allele. No association between the two studied APOA5 polymorphisms (rs662799 and rs3135507) and the biochemical components of glucose, total cholesterol, and triglyceride were observed. On the other hand, a strong statistical association between the high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C) clinical parameters and APOA5 rs662799 CC and rs3135507 AA genotypes was found (p = 0.014 and p = 0.017, respectively). APOA5 polymorphisms rs662799 and rs3135507, with the CC and the AA genotypes, respectively, are associated with increased levels of both high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C) in the Turkish Cypriot population.     

Apolipoprotein A5 polymorphisms in Turkish population: association with serum lipid profile and risk of ischemic stroke

Atherosclerosis, a major cause of ischemic stroke, may be associated with variability of triglyceride (TG) levels. Apolipoprotein A5 (APOA5) genetic polymorphisms are associated with altered TG levels. The objective of this study was to investigate the coding region polymorphisms S19W (rs3135506) and G185C (rs2075291) and the promoter region polymorphism ?1131T>C (rs662799) of the APOA5 gene as risk factors for ischemic stroke in Turkish population. Study group consisted of 272 ischemic stroke patients and 123 controls. Genotypes were determined by real-time polymerase chain reaction (PCR) for S19W and PCR-restriction fragment length polymorphism analysis (PCR–RFLP) for ?1131T>C and G185C. 19W allele frequency was 0.090 in stroke patients and 0.062 in controls (P = 0.191). Minor allele frequencies of ?1131T>C and G185C in patients were 0.106 and 0.004, respectively, and were nearly the same in controls. Total cholesterol and LDL-cholesterol levels were significantly higher for stroke patients having at least one 19W allele compared to non-carriers. A significant difference was also found for LDL-cholesterol levels of stroke patients; higher in ?1131C allele carriers compared to wild type patients. There was a trend for higher frequency of ischemic stroke among ?1131C allele carrier hypertensive, diabetic or obese subjects compared to non-carriers. However, APOA5 genotypes were not associated with the risk of ischemic stroke by logistic regression analysis. The present study demonstrated that carrying rare alleles of APOA5 S19W, ?1131T>C and G185C alone do not constitute a risk for ischemic stroke in the studied Turkish subjects.     

Multiple genetic variants along candidate pathways influence plasma high-density lipoprotein cholesterol concentrations

The known genetic variants determining plasma HDL cholesterol (HDL-C) levels explain only part of its variation. Three hundred eighty-four single nucleotide polymorphisms (SNPs) across 251 genes based on pathways potentially relevant to HDL-C metabolism were selected and genotyped in 3,575 subjects from the Doetinchem cohort, which was examined thrice over 11 years. Three hundred fifty-three SNPs in 239 genes passed the quality-control criteria. Seven SNPs [rs1800777 and rs5882 in cholesteryl ester transfer protein (CETP); rs3208305, rs328, and rs268 in LPL; rs1800588 in LIPC; rs2229741 in NRIP1] were associated with plasma HDL-C levels with false discovery rate (FDR) adjusted q values (FDR_q) < 0.05. Five other SNPs (rs17585739 in SC4MOL, rs11066322 in PTPN11, rs4961 in ADD1, rs6060717 near SCAND1, and rs3213451 in MBTPS2 in women) were associated with plasma HDL-C levels with FDR_q between 0.05 and 0.2. Two less well replicated associations (rs3135506 in APOA5 and rs1800961 in HNF4A) known from the literature were also observed, but their significance disappeared after adjustment for multiple testing (P = 0.008, FDR_q = 0.221 for rs3135506; P = 0.018, FDR_q = 0.338 for rs1800961, respectively). In addition to replication of previous results for candidate genes (CETP, LPL, LIPC, HNF4A, and APOA5), we found interesting new candidate SNPs (rs2229741 in NRIP1, rs3213451 in MBTPS2, rs17585739 in SC4MOL, rs11066322 in PTPN11, rs4961 in ADD1, and rs6060717 near SCAND1) for plasma HDL-C levels that should be evaluated further.     

SLC11A1 Polymorphisms Are Associated with the Risk of Chronic Obstructive Pulmonary Disease in a Korean Population

The solute carrier family 11 member 1 (SLC11A1) protein plays important roles in macrophage activation and displays pleiotropic effects on various macrophage functions, including the regulation of tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta), and oxidative burst. Considering the important roles of macrophage in the pathogenesis of chronic obstructive pulmonary disease (COPD), we hypothesized that the SLC11A1 gene may act as a low-penetrance susceptibility gene for COPD. To test this hypothesis, we first examined the frequencies of 12 candidate polymorphisms in the SLC11A1 gene in 27 healthy Korean individuals, and then genotyped 3 haplotype-tagging polymorphisms [IVS4 + 14G > C (rs3731865), D543 N (rs17235409), and (*)86A > G (rs1059823)] in 83 COPD patients and 203 healthy controls. Individuals with at least one variant allele of the D543 N and (*)86A > G polymorphisms were at a significantly increased risk for COPD compared with carriers with each homozygous wild-type allele [adjusted odds ratio (OR) = 2.23, 95% confidence interval (CI) = 1.24-4.02, P = 0.007; and adjusted OR = 1.92, 95% CI = 1.10-3.35, P = 0.022, respectively]. Consistent with the findings of the genotyping analysis, the 122 haplotype carrying both the 543 N and (*)86G alleles was associated with a significantly increased risk for COPD compared with the 111 haplotype with the 542D and (*)86A alleles (adjusted OR = 2.05, 95% CI = 1.19-3.51, P = 0.009 and Bonferroni corrected P = 0.027). These findings suggest that the SLC11A1 polymorphisms could be used as markers for genetic susceptibility to COPD. However, further studies with large numbers of subjects are needed to confirm our findings.     

Genetic polymorphisms in carnitine palmitoyltransferase 1A gene are associated with variation in body composition and fasting lipid traits in Yup'ik Eskimos

Variants of carnitine palmitoyltransferase 1A (CPT1A), a key hepatic lipid oxidation enzyme, may influence how fatty acid oxidation contributes to obesity and metabolic outcomes. CPT1A is regulated by diet, suggesting interactions between gene variants and diet may influence outcomes. The objective of this study was to test the association of CPT1A variants with body composition and lipids, mediated by consumption of polyunsaturated fatty acids (PUFA). Obesity phenotypes and fasting lipids were measured in a cross-sectional sample of Yup'ik Eskimo individuals (n = 1141) from the Center of Alaska Native Health Research (CANHR) study. Twenty-eight tagging CPT1A SNPs were evaluated with outcomes of interest in regression models accounting for family structure. Several CPT1A polymorphisms were associated with HDL-cholesterol and obesity phenotypes. The P479L (rs80356779) variant was associated with all obesity-related traits and fasting HDL-cholesterol. Interestingly, the association of P479L with HDL-cholesterol was still significant after correcting for body mass index (BMI), percentage body fat (PBF), or waist circumference (WC). Our findings are consistent with the hypothesis that the L479 allele of the CPT1A P479L variant confers a selective advantage that is both cardioprotective (through increased HDL-cholesterol) and associated with reduced adiposity.     

Replication of genetic effects of FTO polymorphisms on BMI in a Korean population

It has been newly reported in recent studies that single-nucleotide polymorphisms (SNPs) in the first intron of the FTO gene have been associated with BMI in whites. To determine whether the gene is associated with BMI in Asians also, we performed a replication study of the association of the gene with BMI in a Korean population. Two SNPs in the FTO gene (rs1421085 and rs17817449) were genotyped using the TaqMan method in a Korean population (n = 1,733). The two SNPs were then used for an association study with BMI through statistical analyses. The rs1421085 C allele (P = 0.0015, effect size = 0.0056) and rs17817449 G allele (P = 0.0019, effect size = 0.0053) were found to be significantly associated with increased BMI. Our results suggest that FTO may be one of the worldwide obesity-risk genes.     

Association of genetic variation in the NR1H4 gene, encoding the nuclear bile acid receptor FXR, with inflammatory bowel disease

ABSTRACT: BACKGROUND: Pathogenesis of inflammatory bowel diseases (IBD), ulcerative colitis (UC) and Crohn's disease (CD), involves interaction between environmental factors and inappropriate immune responses in the intestine of genetically predisposed individuals. Bile acids and their nuclear receptor, FXR, regulate inflammatory responses and barrier function in the intestinal tract. METHODS: We studied the association of five variants (rs3863377, rs7138843, rs56163822, rs35724, rs10860603) of the NR1H4 gene encoding FXR with IBD. 1138 individuals (591 non-IBD, 203 UC, 344 CD) were genotyped for five NR1H4 genetic variants with TaqMan SNP Genotyping Assays. RESULTS: We observed that the NR1H4 SNP rs3863377 is significantly less frequent in IBD cases than in non-IBD controls (allele frequencies: P = 0.004; wild-type vs. SNP carrier genotype frequencies: P = 0.008), whereas the variant rs56163822 is less prevalent in non-IBD controls (allele frequencies: P = 0.027; wild-type vs. SNP carrier genotype frequencies: P = 0.035). The global haplotype distribution between IBD and control patients was significantly different (P = 0.003). This also held true for the comparison between non-IBD and UC groups (P = 0.004), but not for the comparison between non-IBD and CD groups (P = 0.079). CONCLUSIONS: We show that genetic variation in FXR is associated with IBD, further emphasizing the link between bile acid signaling and intestinal inflammation.     

Lipoprotein lipase and apoE polymorphisms: relationship to hypertriglyceridemia during pregnancy.

Pregnancy is associated with increases in plasma total cholesterol (TC) and triglycerides (TG). Individuals with decreased LPL activity have a mild form of hypertriglyceridemia. Variations in the apolipoprotein E (apoE) gene have been associated with increases in plasma TG in addition to differences in plasma TC, LDL cholesterol (LDL-C), and HDL cholesterol (HDL-C). Because of the overproduction of TG-rich VLDL, normal pregnancy challenges the lipolytic capacity of LPL and the clearance of remnants particles. During pregnancy, LPL and apoE polymorphisms may contribute to hypertriglyceridemia. This study investigated the impact of three LPL polymorphisms and the apoE genotypes on lipid levels during pregnancy. Fasting plasma lipids were measured and analyses of the LPL and apoE polymorphisms were performed in 250 women in the third trimester of pregnancy. S447X carriers had lower TG (P = 0.003), and N291S carriers had lower HDL-C (P < 0.02) and higher fractional esterification rate of HDL (FER(HDL)) (P = 0.007), a measure of HDL particle size, than the noncarriers. The E2 allele was associated with lower TC, LDL-C, and FER(HDL) (P < 0.05) compared to the E3/E3 genotype. These findings support that LPL and apoE polymorphisms play an important role in lipid metabolism in pregnancy. The relationship of these polymorphisms to risk of coronary heart disease in women requires further study.