Apolipoprotein E gene polymorphism and dyslipidaemia in adult Asian Indians: A population based study from Calcutta, India

AIM:

The study was aimed to determine the association of Apolipoprotein E (apo E) gene polymorphisms on lipid levels in Asian Indian population.

METHODS:

A total of 350 (184 males and 166 females) adult (30 years and above) Asian Indians of Calcutta and suburb participated in the study. Anthropometric measures, lipids profiles, and blood glucose measures were collected. Out of 350 subjects, a sample of 70 individuals was selected randomly for genotyping after adjusting for age and sex. The apo E gene polymorphisms were determined by agarose gel electrophoresis.

RESULTS:

The apo E polymorphism showed significant association with dyslipidaemia (P=0.0135) with ε3/4 combination has had the highest occurrence of dyslipidaemia and metabolic syndrome (MS) followed by ε4/4 <ε3/3 <ε2/4 <ε2/3 in decreasing order.

CONCLUSIONS:

The ε4 allele of apo E gene independent of other risk factors is associated with dyslipidaemia in particular with low HDLc and high TC: HDLc ratio.     

Apolipoprotein E polymorphism influences postprandial retinyl palmitate but not triglyceride concentrations.

To quantify the effect of the apolipoprotein (apo) E polymorphism on the magnitude of postprandial lipemia, we have defined its role in determining the response to a single high-fat meal in a large sample of (N = 474) individuals taking part in the biethnic Atherosclerosis Risk in Communities Study. The profile of postprandial response in plasma was monitored over 8 h by triglyceride, triglyceride-rich lipoprotein (TGRL)-triglyceride, apo B-48/apo B-100 ratio, and retinyl palmitate concentrations, and the apo E polymorphism was determined by DNA amplification and digestion. The frequency of the apo E alleles and their effects on fasting lipid levels in this sample were similar to those reported elsewhere. Postprandial plasma retinyl palmitate response to a high-fat meal with vitamin A was significantly different among apo E genotypes, with delayed clearance in individuals with an epsilon 2 allele, compared with epsilon 3/3 and epsilon 3/4 individuals. In the sample of 397 Caucasians, average retinyl palmitate response was 1,489 micrograms/dl in epsilon 2/3 individuals, compared with 1,037 micrograms/dl in epsilon 3/3 individuals and 1,108 micrograms/dl in epsilon 3/4 individuals. The apo E polymorphism accounted for 7.1% of the interindividual variation in postprandial retinyl palmitate response, a contribution proportionally greater than its well-known effect on fasting LDL-cholesterol. However, despite this effect on postprandial retinyl palmitate, the profile of postprandial triglyceride response was not significantly different among apo E genotypes. The profile of postprandial response was consistent between the sample of Caucasians and a smaller sample of black subjects. While these data indicate that the removal of remnant particles from circulation is delayed in subjects with the epsilon 2/3 genotype, there is no reported evidence that the epsilon 2 allele predisposes to coronary artery disease (CAD). The results of this study provide not only a reliable estimate of the magnitude of the effect of the apo E polymorphism on various measurements commonly used to characterize postprandial lipemia, but also provide mechanistic insight into the effects of the apo E gene polymorphism on postprandial lipemia and CAD.     

Apolipoprotein A-V: a potential modulator of plasma triglyceride levels in Turks

The apolipoprotein A-V gene (APOA5) plays an important role in determining plasma triglyceride levels. We studied the effects of APOA5 polymorphisms on plasma triglyceride levels in Turks, a population with low levels of HDL cholesterol and a high prevalence of coronary artery disease. We found 15 polymorphisms, three of which were novel. Seven haplotype-tagging single nucleotide polymorphisms (SNPs) were chosen and genotyped in approximately 3,000 subjects. The rare alleles of the -1464T>C, -1131T>C, S19W, and 1259T>C SNPs were significantly associated with increased triglyceride levels (19-86 mg/dl; P < 0.05) and had clear gene-dose effects. Haplotype analysis of the nine common APOA5 haplotypes revealed significant effects on triglyceride levels (P < 0.001). Detailed analysis of haplotypes clearly showed that the -1464T>C polymorphism had no effect by itself but was a marker for the -1131T>C, S19W, and 1259T>C polymorphisms. The -1131T>C and 1259T>C polymorphisms were in a strong but incomplete linkage disequilibrium and appeared to have independent effects. Thus, the APOA5 -1131T>C, S19W, and 1259T>C rare alleles were associated with significant increases in plasma triglyceride levels. At least one of these alleles was present in approximately 40% of the Turks. Similar associations were observed for -1131T>C and S19W in white Americans living in San Francisco, California.     

Apolipoprotein B gene polymorphism and plasma lipid levels in phenylketonuric children

The associations of apolipoprotein B (apoB) gene polymorphisms with blood lipid levels, also accounting for apo E polymorphisms, were assessed in 82 phenylketonuric (PKU) children on diet (34 girls, 48 boys, age 4-12 years, median 8 years). Dietary and plasma biochemical assessments were performed at six-month intervals from the age of 24 months onwards. Apo B (XbaI, MspI, EcoRI restriction sites) and apo E (E2, E3, E4) gene polymorphisms were determined by restriction-enzyme analysis after DNA extraction from blood. Subgroups of apoB polymorphisms were similar for energy intake, dietary lipids and distribution of apo E polymorphisms. Children carrying XbaI X+ / X+ showed higher plasma levels of LDL cholesterol than children carrying X- / X-/+. This gene-related response to dietary habits might play a role also in non-PKU individuals fed low-fat, low-cholesterol diets.     

Apolipoprotein B signal peptide insertion/deletion polymorphism is associated with Ag epitopes and involved in the determination of serum triglyceride levels.

We have investigated the insertion/deletion polymorphism in the signal peptide region of the apoB gene in 106 Finnish individuals from North Karelia. The relative frequency of the insertion allele in this sample was 0.73. Strong linkage disequilibrium was detected between this apoB insertion/deletion polymorphism and the Ag(c/g) epitope pair of apoB, while weak linkage disequilibrium was detected between the polymorphism and the four other reported Ag epitope pairs [(a1/d), (x/y), (h/i) and (t/z)], as well as the apoB PvuII and the XbaI RFLPs. Using one-way analysis of variance there was a statistically significant association (P less than 0.05) between the apoB insertion/deletion polymorphism and serum triglyceride levels in this sample. Individuals homozygous for the insertion allele had higher triglyceride levels than individuals homozygous for the deletion allele, while individuals heterozygous for the polymorphism had intermediate levels. These differences were reduced when individuals were consuming a low fat diet but were statistically significant when the individuals returned to their normal diet. It is possible that insertion or deletion of three hydrophobic amino acids (leu-ala-leu) from the signal peptide of apoB may have a direct effect on plasma triglyceride levels by altering the intracellular processing of apoB or apoB-containing lipoproteins in the liver or intestine.     

Apolipoprotein B 3'-VNTR polymorphism in the Udmurt population

An analysis of a highly polymorphic region of the apolipoprotein B gene 3'-end DNA (Apo B 3'-VNTR), represented by 10 alleles, was carried out using the polymerase chain reaction. Data inferred from the principal component analysis indicate that the Udmurts occupy an isolated position among the populations constituting the northern branch of Caucasoid peoples.     

Apolipoprotein E polymorphism and its association with serum lipid levels in Brazilian children

The influence of apolipoprotein E (APOE) genotypes on plasma lipid levels was determined in 414 Brazilian healthy children of mixed ethnicity, age 5 to 15 years (mean 8.9+/-2.9). The APOE*3 allele was the most frequent (77%), followed by APOE*4 (17%) and APOE*2 (6%). The pattern of lipid differences among genotypes was similar in both boys and girls. We did not detect an increase in cholesterol levels with the presence of the APOE*4 allele. Because a growing body of evidence suggests that the effect of *4 depends on its interaction with diet, the frequency of *4 might be more variable in children than in adults as well as among populations. Children carrying a *2 allele had lower total cholesterol (TC) and LDL-cholesterol levels (138.47+/-24.32 and 77.72+/-19.42, respectively) compared with *3/*3 children (158.33+/-25.28 and 97.05+/-21.82, respectively). Mean TC/HDLC ratio was also lower in children with the APOE*2 allele (3.27+/-0.66 versus 3.64+/-0.76). In this highly admixed population sample, the *2 anti-atherogenic lipid pattern is already detected in children.     

Hepatic glucokinase promoter polymorphism is associated with hepatic insulin resistance in Asian Indians.

Background  

The role of glucokinase (GCK) in the pathogenesis of maturity-onset diabetes of the young is well established. However, its role in the common form of type 2 diabetes is far from convincing. We investigated the role of the G-to-A polymorphism in the hepatic GCK promoter on insulin sensitivity and beta cell function in 63 normotensive Asian Indians with normal glucose tolerance. As proposed by Matsuda and DeFronzo, hepatic insulin sensitivity (ISI_H) and total body insulin sensitivity (ISI_M) were estimated from the oral glucose tolerance test. Beta cell function was estimated using %B from the Homeostasis Model Assessment and insulingenic index (dI/dG).     

Apolipoprotein E polymorphism in Saudis

Apolipoprotein E (apoE) genotypes were determined in 165 Saudis. The prevalence of genotype, E3/E3, E3/E4 and E4/E4 was found to be 71, 27 and 2% respectively. The E3/E3 was the most prevalent genotype among the Saudis followed by E3/E4. However, other genotypes E2/E2, E2/E3 and E2/E4 were absent showing the absence of E2 allele in the test population. The high frequencies of the E3 allele (0.845) and E3/E3 genotype (0.71) and absence of E2 allele in Saudis under study are similar to those reported earlier for Native Americans, Mexican-Americans, Mayans, Cayapa, Mazatecan Indians and Mexican Mestizos populations.     

Apolipoprotein E polymorphism in Saudis

Apolipoprotein E (apoE) genotypes were determined in 165 Saudis. The prevalence of genotype, E3/E3, E3/E4 and E4/E4 was found to be 71, 27 and 2% respectively. The E3/E3 was the most prevalent genotype among the Saudis followed by E3/E4. However, other genotypes E2/E2, E2/E3 and E2/E4 were absent showing the absence of E2 allele in the test population. The high frequencies of the E3 allele (0.845) and E3/E3 genotype (0.71) and absence of E2 allele in Saudis under study are similar to those reported earlier for Native Americans, Mexican-Americans, Mayans, Cayapa, Mazatecan Indians and Mexican Mestizos populations.     

Apolipoprotein A-IV polymorphism in man

Summary In man, apolipoprotein A-IV is characterized by a genetically determined polymorphism controlled by two codominant alleles. Two isoforms of this apolipoprotein, designated A-IV-1 and A-IV-2, can be identified by isoelectric focusing. Among 1000 healthy factory workers participating in an epidemiological study, A-IV-1 (genotype 1-1) was observed in 85%; A-IV-2 (genotype 2-2), in 0.5%; and A-IV-1 in combination with A-IV-2 (genotype 1–2), in 14%. In four nonrelated subjects, an apolipoprotein A-IV variant (A-IV-Münster), characterized by a slightly more basic isoelectric focusing behavior than A-IV-2, was detected in combination either with A-IV-1 or A-IV-2. Mendelian inheritance of this variant could be demonstrated.     

Apolipoprotein E polymorphism in the Netherlands and its effect on plasma lipid and apolipoprotein levels

Summary By isoelectric focusing of delipidated sera followed by immunoblotting we studied the apolipoprotein (apo) E polymorphism in 2018 randomly selected 35-years-old males from three different areas in the Netherlands. Comparison of the APOE allele (E^*2, E^*3, and E^*4) frequencies estimated in this study with those reported for several other population samples showed that there are marked differences between the Dutch population and the populations of Japan, New Zealand, Finland, and the United States. These differences in APOE allele frequencies appeared to be mainly due to differences in frequencies of the E^*2 allele (decreased in Japan and Finland; increased in New Zealand) and the E^*4 allele (increased in Finland; decreased in Japan and the United States). No difference in APOE allele frequencies was found between the Dutch population and the populations of West Germany and Scotland. Measurements of plasma cholesterol and apo B and E concentrations showed that the E^*4 allele is associated with elevated plasma cholesterol and apo B levels and with decreased apo E concentrations, whereas the opposite is true for the E^*2 allele. In the Dutch population, the sum of average allelic effects of the common APOE alleles on plasma cholesterol and apo B levels is 6.8% and 14.2%, respectively, of the total population mean. The total average allelic effect on plasma apo E concentrations was more pronounced (50.1%), suggesting that the APOE alleles primarily affect apo E concentrations rather than plasma cholesterol and apo B levels. This hypothesis is sustained by the observation that for plasma apo E levels the genetic variance associated with the APOE gene locus contributed about 18% to the total phenotypic variance. For plasma cholesterol and apo B this contribution was only 1.4% and 2.3% and is relatively low as compared with that reported for other population samples.     

猪apoC3基因的遗传变异分析

目的:探究猪apoC3基因多态性,为进一步探讨其对脂肪沉积的影响和表达调控等研究提供依据。方法:选取具有不同脂肪沉积特点的3个猪种(可乐猪、贵州白香猪和大约克猪)构建品种DNA池并进行测序,结合各SNP位点测序峰高比值估算等位基因频率,并利用在线软件对不同基因型的转录结合位点及mRNA二级结构进行预测。结果:在3个猪种的apoC3基因中共发现17个SNPs(2个位于5’侧翼区;1个位于外显子3中,为同义突变;1个位于3’非翻译区,其它13个分别位于3个不同内含子中),其中C813G变异增加了一个转录因子GATA-2结合位点,G2280A变异导致mRNA二级结构最小自由能增加0.4kkal/mol。结论:不同猪种间apoC3基因SNPs位点等位基因频率差异较大,而apoC3基因编码区相对保守。     

C3 polymorphism in Greece

The polymorphism of the third component of the human complement (C3) was investigated in a sample of 1,055 unrelated healthy individuals from nine different areas of Greece. The estimated gene frequencies were: C3S = 0.786 and C3F = 0.211. Three individuals were found to have rare variant C3 types. The allele frequencies resemble those reported for other Caucasian populations.     

MICA polymorphism in South American Indians

We have studied the MICA alleles of 196 unrelated subjects from three South American Indian tribes (Toba, Wichi and Terena). They are members of isolated tribes located in the Gran Chaco area in northeastern Argentina and in Mato Grosso do Sul in South Central Brazil. Of 55 previously known alleles, nine were observed in South American Indians, compared with 16 that were found in North American Caucasians, suggesting a more restricted allelic distribution of MICA in these tribes. In South American Indians, MICA*00201 was the most frequent allele, with a gene frequency of 33% in Toba, 47% in Wichi and 44% in Terena. MICA*00201, MICA*027 (external domain sequence like MICA*008/TM allele A5) and MICA*010 accounted for more than 90% of all the MICA genes in South American Indians. In North American Caucasians, MICA*00801 (*008/A5.1) accounted for 42% of the genes and was the most common allele. We observed a high degree of linkage disequilibrium between certain alleles of MICA and of HLA-B in the South American Indian populations. Phylogenetic trees constructed using gene frequencies of the transmembrane short tandem repeats in the populations reported here, and in other populations taken from published reports, suggest that South American Indians are more closely related to Asians than to Europeans.     

Genetic polymorphism of apolipoprotein C polypeptide in native Asian sheep

The frequency distributions of apolipoprotein C alleles in native Asian sheep (Bengal, Kagi, Lampuchhre, Vietnamese, Myanmar, Baruwal, Bhyanglung, Khalkhas, and Kuwait) were determined using a one-dimensional polyacrylamide gel isoelectric-focusing immunoblotting technique. Among these Asian sheep, the genetic locus consisted mainly of two common APOC*1 and APOC*3 alleles. The Baruwal sheep most frequently possessed APOC*1 (0.9881), showing significant differences from all other Asian sheep in allele frequency (0.7195-0.9032, P < 0.02). Compared with European sheep tested previously, these Asian sheep had significantly higher frequencies of APOC*1 (0.7828 and 0.7127 averages, P < 0.0005) and APOC*3 (0.2162 and 0.11 averages, P < 0.0001). In particular, APOC*2 was detected at an extremely low frequency (0.0025) in the Khalkhas sheep only, and was uncommon in all Asian sheep (0.001 average), in contrast with the 0.1773 average of European sheep (P < 0.00001). This finding suggests that APOC*2 is exceedingly rare in Asian sheep. With the exception of triglycerides and VLDL cholesterol in the Vietnamese sheep, no phenotypic effects on plasma lipid and lipoprotein levels in the Asian sheep tested were seen.     

Soyasapogenols reduce cellular triglyceride levels in 3T3-L1 mouse adipocyte cells by accelerating triglyceride lipolysis

Soyasapogenol is a soyasaponin aglycone, which has been suggested to exert a more potent function than the glycoside form. In this study, the effect of soyasapogenol A and B on cultured adipocyte cell function was investigated using mouse 3T3-L1 adipocyte cells. 3T3-L1 cells were treated with insulin, dexamethasone, and 3-isobutyl-1-methylxanthine for differentiation to adipocytes, and the cells were then cultured in the presence of soyasapogenol A or B (6.25 or 12.5 µM). The media were harvested and refreshed every 2 d. After a 10 d culture, the cells were harvested and the triglyceride content of the cells was determined. The triglyceride content of soyasapogenol B-treated cells was significantly lower than those of vehicle-treated cells. Glycerol and free fatty acid levels in the soyasapogenol-treated cell media were higher than those in vehicle cells. However, there was no difference in the level of adipose triglyceride lipase among soyasapogenol A-, soyasapogenol B-, and vehicle-treated cells. The secreted adiponectin and resistin levels of soyasapogenol-treated cell media were also different compared with those of vehicle-treated cells. Especially, the secreted resistin level in soyasapogenol B-treated cell media was obviously reduced compared with that of vehicle-treated cells. Taken together, these results suggest that soyasapogenol B exerted an anti-obesity and anti-diabetic effect on adipocytes by lowering the cellular triglyceride level by accelerating triglyceride lipolysis with reduced resistin secretion.     

Genetic polymorphism of C3 and serum levels of immunoglobulins,C3, C4 components of complement and C3-proactivator in four different populations of Afghanistan

Summary The C3 phenotype distribution was studied in 4 different populations from Afghanistan. The gene frequencies of C3^s allele were: Tajiks (0.8547), Pushtoons (0.8812), Hazaras (0.9036) and Osbeks (0.8530). These values were significantly higher than in European populations studied previously. No significant differences were found between the mean serum levels of C3, C4 and C3-proactivator among 4 population groups. A higher concentration of IgG, IgA and IgM was observed in Afghanistan sera than reported for Europeans.Supported by the Stiftung Volkswagenwerk.Dedicated to Prof. J. Kühnau on his 75th birthday.     

Apolipoprotein E gene polymorphism and serum lipid levels in the Guangxi Hei Yi Zhuang and Han populations

Hei Yi Zhuang is an isolated subgroup of the Zhuang minority in China. Little is known about the distribution of apolipoprotein (apo) E genetic variations and its role in lipid metabolism in this population. The present study was undertaken to compare the effect of apoE gene polymorphism on serum lipid levels between the Guangxi Hei Yi Zhuang and Han populations. A total of 873 subjects of Hei Yi Zhuang and 867 participants of Han Chinese were surveyed by a stratified randomized cluster sampling. Genotyping of apoE was performed using polymerase chain reaction and restriction fragment length polymorphism. The frequencies of 2, 3, and 4 alleles were 15.23%, 79.84%, and 4.93% in Hei Yi Zhuang, and 9.23%, 81.43%, and 9.34% in Han (P < 0.001); respectively. The frequencies of 2/ 2, 2/ 3, 2/ 4, 3/ 3, 3/ 4, and 4/ 4 genotypes were 4.70%, 17.86%, 3.21%, 68.16%, 5.50%, and 0.57% in Hei Yi Zhuang, and 2.54%, 9.23%, 4.15%, 70.70%, 12.23%, and 1.15% in Han (P < 0.001); respectively. Total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), and apoB levels were lower in Hei Yi Zhuang than in Han (P < 0.01-0.001), but high-density lipoprotein cholesterol (HDL-C) levels and the ratio of apoA-I to apoB were higher in Hei Yi Zhuang than in Han (P < 0.001 for each). There were significant differences in TC, HDL-C, LDL-C, and apoB levels among the six genotypes in both ethnic groups (P < 0.01-0.001). Hyperlipidemia was positively correlated with age, body mass index, hypertension, alcohol consumption, and apoE allele in both populations (P < 0.05-0.001). TC, LDL-C, and apoB levels were positively correlated, and HDL-C levels were negatively associated with apoE genotypes in both ethnic groups (P < 0.001 for all). The differences in the lipid profiles between Hei Yi Zhuang and Han Chinese might partly attribute to the differences in apoE genotypic and allelic frequencies.