Lipoprotein Lipase Gene Polymorphisms Research Articles

참돔의 lipoprotein lipase 유전자 다형성

Polymorphism of the lipoprotein lipase (LPL) gene which plays an important role in regulation of lipid deposition was analysed in two red seabream (pagrus major) populations (KF4, cultured KORDI line, n=100 : JPN, imported from Japan, n=100). We amplified a DNA fragment (1,091 bp) including the exon 2 region of the LPL gene, and conducted PCR-RFLP analysis using MspI and AluI. The PCR products were also sequenced. Two alleles (A and B) were found in MspI digestion and Sve alleles (A, B, C, D and E) in AluI digestion. The sequenced data revealed four nucleotide substitutions including one transversion at the MspI recognition site (nt 2,235, <TEX>$C{\rightarrow}10$</TEX>) and three transitions at the AluI recognition sites (nt 1,721, <TEX>$A{\rightarrow}G;$</TEX> nt 2,319, <TEX>$C{\rightarrow}T;$</TEX> nt 2,319, <TEX>$T{\rightarrow}C$</TEX>). Among them, substitutions at the nt 2,235 and 2,319 sites which are located in the exon 2 were proved to be silent point mutations. MspI polymorphism resulted in 3 genotypes, and the allele frequency was significantly different between the two fish populations, KF4 and JPN. In the case of AluI polymorphism, the 5 alleles (A, B, C, D, E) comprised 12 genotypes of the 5 alleles. KF4 population, alleles D and I were specific to the LPL gene Polymorphisms would be useful DNA markers for red seabream population.

Lipoprotein lipase gene polymorphism and lipid profile in coronary artery disease.

Lipoprotein lipase (LPL) plays a central role in lipid metabolism, hydrolyzing triglyceride in chylomicrons and very-low-density lipoproteins. The PvuII polymorphic variant of LPL gene is common and might affect risk of coronary artery disease (CAD). Our aim was to determine whether LPL- PvuII polymorphism can be considered to be an independent risk factor or a predictor for CAD in Turkish subjects. We used polymerase chain reaction and restriction enzyme digestion to determine the distribution of the previously described C-->T transition that causes a PvuII polymorphism in intron 6 among healthy blood donors of Turkish origin and among angiographically confirmed CAD patients with comparable ethnic backgrounds. For the PvuII genotypes, within the CAD group (n = 80), the +/- genotype was found in 39 individuals (48.8%), whereas 25 (31.3%) carried the +/+ genotype, and 14 (17.5%) carried the -/- genotype. Within the control group (n = 49), the -/- genotype was found in 19 individuals (38.8%), 16 (32.7%) carried the +/- genotype, and 14 (28.6%) carried the +/+ genotype. The genotype frequency distribution was significantly different (P =.049) in the CAD and control study groups. The most frequent genotype among CAD patients was +/-; this genotype was more frequent in patients than in control subjects. However, the -/- genotype was more prevalent in the control group. Lipoprotein lipase-PvuII polymorphism was found to be associated with fasting total cholesterol and low-density lipoprotein cholesterol levels. The +/+ genotype was found to have higher levels of total cholesterol and low-density lipoprotein cholesterol in both the CAD and control groups. There was a difference in the distribution of LPL-PvuII genotypes between the healthy subjects and the patients with CAD. Lipoprotein lipase-PvuII polymorphisms were not detected as independent risk factors for CAD in this study group, but had associations with lipid levels.

Pair-wise detection of eight common DNA polymorphisms of the human lipoprotein lipase gene by PCR-RFLP. Findings of the Olivetti Heart Study

We developed a rapid procedure to analyse simultaneously two different DNA polymorphisms of the human LPL gene by PCR-RFLP (Polymerase Chain Reaction-Restriction Fragment Length Polymorphism). The method involves PCR amplification of the gene fragments encompassing two polymorphic sites, direct digestion in the same PCR-tube of the amplification mixture with two restriction enzymes, and the analysis of the resulting DNA fragments by gel electrophoresis. In 422 participants of the 1994 follow-up examination of the Olivetti Heart Study, a total of eight common LPL gene polymorphisms have been analysed in pairs by this procedure: −93 T/G and D9N; V108V and T361T; N291S and PvuII; HindIII and S447X. Two of these polymorphisms (V108V and T361T) were analysed for the first time. This method is suitable for the routine analysis of clinical samples of varying DNA content and practically halves the times and costs of screening for these LPL polymorphisms.

Association of lipoprotein lipase gene polymorphism with risk of prostate cancer in a Japanese population.

A high fat intake has been associated with prostate cancer risk, and gene polymorphisms of lipoprotein lipase (LPL) play an important role in plasma lipoprotein metabolism. We herein analyzed the association of LPL gene polymorphisms with the risk of prostate cancer in a Japanese population. Three single nucleotide polymorphisms (SNPs) of LPL designated as Ser447stop, HindIII and PvuII were genotyped by the polymerase chain reaction-restriction fragment length polymorphism method in 273 prostate cancer patients, 205 benign prostatic hyperplasia (BPH) patients and 230 male controls. The men with the CG + GG genotypes of the Ser447stop polymorphism had an increased risk of prostate cancer compared to those with the CC genotype [age-adjusted odds ratio (aOR) = 1.625; 95% CI = 1.068-2.471; p = 0.023]. Furthermore, the increased risk associated with the CG + GG genotypes was more strongly observed in patients with high-grade cancers (aOR = 2.843; 95% CI = 1.252-6.458; p = 0.039) or metastatic diseases (aOR = 2.300; 95% CI = 1.042-5.074; p = 0.013), whereas the risk was not significant in those with low- to intermediate-grade cancers or nonmetastatic diseases. In the HindIII and PvuII polymorphisms, there was no significant difference between the prostate cancer patients and the controls, and no significant results as for tumor grade and stage. None of the 3 polymorphisms showed any association with the risk of BPH. Our results suggest that the LPL Ser447stop polymorphism is a common genetic modifier for the development of prostate cancer, particularly that of high-grade and/or high-stage, in a Japanese population.

Pairwise detection of eight common DNA polymorphisms of the human lipoprotein lipase (LPL) gene by PCR-RFLP: Findings of the olivetti prospective heart study

Pairwise detection of eight common DNA polymorphisms of the human lipoprotein lipase (LPL) gene by PCR-RFLP: Findings of the olivetti prospective heart study

Postprandial triglyceride levels in familial combined hyperlipidemia. The role of apolipoprotein E and lipoprotein lipase polymorphisms

The effect of apolipoprotein E genotype and polymorphisms of lipoprotein lipase gene on plasma postprandial triglyceride levels in familial combined hyperlipidemic subjects and their relatives have not been sufficiently studied. This study included sixteen familial combined hyperlipidemic parents (G1): age: 52 ± 9 years with total-cholesterol: 7.2 ± 1.7 mmol/L, fasting triglycerides: 2.8 ± 1.4 mmol/L and sixteen children (G2) (twelve were normolipidemic): of age: 22 ± 5 years with total-cholesterol: 5.2 ± 1.1 mmol/L, fasting triglycerides: 2.06 ± 1.8 mmol/L and twelve normolipidemic, healthy controls. Blood samples were taken fasting and 2, 4, 6, 8, 10 hr postprandially after the standard fat rich test meal. We determined lipid parameters, apolipoprotein E and lipoprotein lipase HindIII and PvuII polymorphisms as well. The 6-hr critical postprandial triglyceride values were abnormal in both G1: 5.88 ± 2.7 mmol/L and G2: 3.53 ± 2.7 mmol/L (p <0.001), respectively, and differed significantly (p <0.001) from each other. The subjects of familial combined hyperlipidemic families with E4 allele in both generations exhibited significantly (p <0.001) higher and extended postprandial lipemia. We did not find significant effects of lipoprotein lipase HindIII or PvuII polymorphisms on the fasting lipid values alone, however in normolipidemic subjects from the same families the homozygosity of HindIII variation was associated with higher triglyceride postprandial peak (p <0.01). The main findings of our study are that i.) normolipidemic G2 subjects in familial combined hyperlipidemic families have already abnormal postprandial status, and ii.) the 6 h postprandial triglyceride values were correlated with fasting triglyceride levels, which showed association with the apolipoprotein E4 allele.

Lack of association of lipoprotein lipase gene polymorphisms with coronary artery disease in the Saudi Arab population.

Previous studies reported an association of certain polymorphisms in the lipoprotein lipase (LPL) gene with the risk of coronary artery disease (CAD); however, these studies were small and inconsistent. In addition, none of these studies attempted to establish such an association in the Arab population. To determine whether 2 LPL polymorphisms (LPL-HindIII and LPL-PvuII located on introns 8 and 6, respectively, of the LPL gene) can be considered as independent risk factors or as predictors for CAD in Arabs. We used polymerase chain reaction and restriction enzyme digestion to determine the distribution of the LPL-HindIII and LPL-PvuII polymorphisms among healthy blood donors of Arabic origin (BD group) and angiographically confirmed CAD patients (CAD group) with identical ethnic backgrounds. For the HindIII genotypes, within the BD group (n = 410), the +/+ genotype was found in 206 individuals (50.2%), 173 (42.2%) carried the +/- genotype, and 31 (7.6%) carried the -/- genotype. Within the CAD group (n = 352), the +/+ genotype was found in 189 individuals (53.7%), 138 (39.2%) carried the +/- genotype, and 25 (7.1%) carried the -/- genotype. P values of.38,.45, and.92 were obtained for the +/+, +/-, and -/- genotypes, respectively. For the PvuII genotypes, within the BD group (n = 511), the +/+ genotype was found in 182 individuals (35.6%), 248 (48.5%) carried the +/- genotype, and 81 (15.9%) carried the -/- genotype. Within the CAD group (n = 431), the +/+ genotype was found in 138 individuals (32%), 225 (52.2%) carried the +/- genotype, and 68 (15.8%) carried the -/- genotype. P values of.28,.29, and.98 were obtained for the +/+, +/-, and -/- genotypes, respectively. The distribution and the allele frequency of these 2 LPL variants were similar in CAD and BD study groups and followed the Hardy-Weinberg equilibrium. There was no difference in the distribution of both LPL polymorphisms between the healthy group and the CAD group. Therefore, these 2 LPL polymorphisms cannot be considered as independent risk factors or as predictors for CAD in this population.

Lack of association of lipoprotein lipase gene polymorphisms with coronary artery disease in the Saudi Arab population.

Abstract Context.—Previous studies reported an association of certain polymorphisms in the lipoprotein lipase (LPL) gene with the risk of coronary artery disease (CAD); however, these studies were small and inconsistent. In addition, none of these studies attempted to establish such an association in the Arab population. Objective.—To determine whether 2 LPL polymorphisms (LPL-HindIII and LPL-PvuII located on introns 8 and 6, respectively, of the LPL gene) can be considered as independent risk factors or as predictors for CAD in Arabs. Design.—We used polymerase chain reaction and restriction enzyme digestion to determine the distribution of the LPL-HindIII and LPL-PvuII polymorphisms among healthy blood donors of Arabic origin (BD group) and angiographically confirmed CAD patients (CAD group) with identical ethnic backgrounds. Results.—For the HindIII genotypes, within the BD group (n = 410), the +/+ genotype was found in 206 individuals (50.2%), 173 (42.2%) carried the +/− genotype, and 31 (7.6%) carrie...

Dietary long-chain n-3 PUFAs increase LPL gene expression in adipose tissue of subjects with an atherogenic lipoprotein phenotype

We sought to test the hypothesis that dietary long-chain n-3 PUFA (LC n-3 PUFA) in fish oil stimulate the gene expression of lipoprotein lipase (LPL) in human adipose tissue (AT). In a randomized, double blind, placebo-controlled, cross-over study, 51 male subjects expressing an atherogenic lipoprotein phenotype (ALP) had their diets supplemented with fish oil for 6 weeks. As we previously reported for this group, supplementation with LC n-3 PUFA produced a decrease in fasting plasma triglyceride (TG) (-35%, P < 0.05), attenuation of the postprandial TG response (area and incremental area under the curve; AUC and IAUC, P < 0.05), and a decrease in small, dense LDL. The present study extended these observations by showing that these changes were accompanied by a marked increase in the concentration of LPL mRNA in adipose tissue (AT-LPL mRNA, +55%, P = 0.003) and post-heparin LPL activity (PH-LPL, +31%, P = 0.036). There was also evidence of an association between LPL gene expression and polymorphism in the apolipoprotein E gene. We conclude that the favorable influence of dietary n-3 PUFA on the ALP may be mediated, in part, through an increase in the plasma activity and gene expression of lipoprotein lipase in human adipose tissue.

Common mutations in the lipoprotein lipase gene (LPL): effects on HDL-cholesterol levels in a Chinese Canadian population

Background: favorable lipid profiles including low total serum cholesterol (TC), TC/HDL-cholesterol (HDL-C) ratio and elevated HDL-C levels have been previously reported in Chinese living in China. More recent data, however, suggests a changing trend toward decreased HDL-C and increased TC and LDL cholesterol (LDL-C) in Chinese populations. Environmental factors likely contribute, in part, to these findings. However, genetic factors contributing to lipoprotein metabolism may also play a role in determining the lipid/lipoprotein phenotype observed in Chinese populations. Lipoprotein lipase (LPL) mutations have been associated with altered HDL-C concentrations in Caucasians but have not yet been studied in a large population of Chinese descent. Methods: 1577 Chinese Canadians of Cantonese descent were recruited for a cardiovascular risk factor study. The frequency and effect of three LPL gene polymorphisms [Asp9Asn (D9N, n=374), Asn291Ser (N291S, n=321) and Ser447-Ter (S447X, n=403)] on serum HDL-C concentrations was assessed. All the three polymorphisms have been shown to alter HDL-C levels in different Caucasian populations. Results: lower TC, LDL-C, and TG and higher HDL-C were observed in both male and female Chinese Canadian subjects compared to other population samples. The D9N and N291S LPL polymorphisms were identified in 1/374 (0.3%) and 5/321 (1.6%) subjects, respectively. Carrier frequency of the S447X mutation was (102/403) 25.3%. This S447X polymorphism was observed with higher frequency in males with HDL-C levels in the highest tertile compared with those in the lowest HDL-C tertile (carrier frequencies 37.3 vs. 19.4%) ( P=0.046). Conclusion: in this cohort of Chinese Canadians, the serum lipid profiles were more favorable than what has been reported for Caucasian Canadians. A favorable spectrum of polymorphisms in the LPL gene may mitigate the adverse effects of western lifestyle on plasma lipoproteins in this cohort of Cantonese Canadians.

Lipoprotein lipase gene polymorphism, cholesterol subfractions and myocardial infarction in large samples of the general population

Genetic variants of the lipoprotein lipase gene have been associated with dyslipidemia and coronary artery disease. However, data have been inconsistent and are mainly based on selected predominantly male patient groups. We evaluated the influence of the HindIII restriction fragment length polymorphism on lipid levels in the general population (1361 participants of a large population-based survey from Augsburg, Germany; 50% women) as well as the association of this polymorphism with the risk of myocardial infarction (MI; genotype frequencies in 1159 patients with documented MI under 60 years of age). In the population-based survey, a highly significant association between the frequent H2H2 genotype and unfavorable cholesterol subfraction levels was observed in men and in postmenopausal women whereas no significant association was observed in premenopausal women (uni- and multivariate analysis). Such unfavorable lipid levels in homozygotes for the H2 allele may be expected to be associated with a 19-25% increased risk to suffer from myocardial infarction (MI). Nevertheless, genotype and allele frequencies in the general population were not different from those in patients with previous MI (H2H2 genotype frequency 51.3% vs. 53.2%, respectively; P=0.63). This large study shows that the H2H2 genotype of the lipoprotein lipase gene polymorphism is associated with unfavorable lipid levels. Estrogen status may modulate this association in women. The effects of the genotype on lipid levels were apparently not strong enough to reveal a significant association with MI.

Association of lipoprotein lipase gene polymorphisms with coronary artery disease

OBJECTIVESThe purpose of this study was to test whether the HindIII (+) and PvuII (−) or (+) restriction enzyme–defined alleles are associated with angiographic coronary artery disease (CAD).BACKGROUNDLipoprotein lipase (LPL) plays a central role in lipid metabolism, hydrolyzing triglyceride in chylomicrons and very low density lipoproteins. Polymorphic variants of the LPL gene are common and might affect risk of CAD.METHODSBlood was drawn from 725 patients undergoing coronary angiography. Leukocyte deoxyribonucleic acid segments containing the genomic sites were amplified by the polymerase chain reaction and digested, and polymorphisms were identified after electrophoresis in 1.5% agarose gel.RESULTSIn no-CAD control subjects (n = 168), HindIII (−) and (+) allelic frequencies were 28.6% and 71.4%, and (−) and (+) alleles were carried by 44.0% and 86.9% of subjects, respectively. Control PvuII (−) and (+) allelic frequencies were 41.7% and 58.3%, and (−) and (+) alleles were carried by 64.3% and 81.0%, respectively. In CAD patients (>60% stenosis; n = 483), HindIII (+) allelic carriage was increased (93.8% of patients, odds ratio [OR] = 2.28, confidence interval [CI] 1.27 to 4.00). Also, PvuII (−) allelic carriage tended to be more frequent in CAD patients (OR = 1.33, CI 0.92 to 1.93). Adjusted for six CAD risk factors and the other polymorphism, HindIII (+) carriage was associated with an OR = 2.86, CI 1.50 to 5.42, p = 0.0014, and PvuII (−) carriage, OR = 1.42, CI 0.95 to 2.12, p = 0.09. The two polymorphisms were in strong linkage disequilibrium, and a haplotype association was suggested.CONCLUSIONSThe common LPL polymorphic allele, HindIII (+), is moderately associated with CAD, and the PvuII (−) allele is modestly associated (trend). Genetic variants of LPL deserve further evaluation as risk factors for CAD.

Incidence of Lipoprotein Lipase Gene Polymorphism and Correlation with Severity of Coronary Artery Disease in Korean

Background:Lipoprotein lipase (LPL) is a key enzyme in the metabolism of serum triglyceride (TG) which is utilized in the peripheral tissue as free fatty acid and stored in adipose tissue. LPL gene consists of 10 exons which encode 475 amino acids and more than 9 LPL gene polymorphisms have been reported. LPL gene polymorphism is related to lipids level and the severity of atherosclerosis in coronary artery disease. In Korea, LPL polymorphism has not been reported yet. The purpose of this study is to know the incidences of LPL gene polymorphism and it's relationship with blood lipids level and the severity of atherosclerosis. Methods:Subjects were divided into three groups;normal controls (n=50), coronary artery disease (CAD, n=51) and cerebrovascular disease (CVD, n=52). The PCR-amplified genomic DNA from peripheral white blood cell was analyzed with restriction fragment length polymorphism (RFLP) by two different restriction enzymes (Pvu II, Hind III). Results:Total cholesterol (TC) was higher in CVD than in controls and CAD (203±60 mg/dl vs 188±37, 167±42, p<0.01). Triglyceride (TG) was also elevated in CAD (166±65 mg/dl vs 122±62 in controls, p<0.05). HDL cholesterol (HDL-C) was higher in controls than in CVD and CAD (49 ±9 mg/dl vs 36±10, 44±9, p<0.05). The incidence of Hind III RFLP and Pvu II RFLP was not different among groups. There was no correlation between LPL gene RFLP and lipid profile. There was no correlation between LPL gene RFLP and severity of coronary arterial stenosis. The incidence of Hind III RFLP (-/-) homozygotes was lower in Korean than in other country (5% vs 7-10%). The incidence of Pvu II RFLP (/-) homozygotes was lower in Korean than in other country (10.3% vs 18-29%). Conclusions:The LPL gene mutations in intron 6 and 8 have no direct effects on the lipid profiles and the severity of coronary artery disease. Although LPL is a key enzyme in TG metabolism, two mutations in this study could not change the activity of LPL, nor were a marker linked to other site of mutation (s). The mutation (s) in exon which encode 논문접수일:1998년 12월 23일 심사완료일:1999년 3월 8일 교신저자:전은석, 301-040 대전시 중구 대사동 640 충남대학교 의과대학 내과학교실 전화:(042) 220-7157·전송:(042) 257-5753 E-mail:esjeon@cnuh.chungnam.ac.kr

Association of Lipoprotein Lipase Gene Polymorphism and Coronary Artery Disease in Korean

Background:The accumulation of lipoprotein and monocyte in the intima of the arterial wall is the most important step of the development of coronary artery disease (CAD). Lipoprotein lipase (LPL) plays an antiatherogenic role by lipolysis of triglyceride-rich lipoproteins, but, it may also act as a receptor of some lipoproteins and monocyte at the arterial wall and act as a atherogenic molecule. Previous studies showed somewhat contradictory results about the association of CAD and LPL polymorphisms and mutations. Racial and dietary difference may contribute to these contradictory results. In this study, we tried to find out the association of CAD and the genetic variation of the LPL (PvuII RFLP in intron 6, HindIII RFLP in intron 8 and Ser 447 Ter mutation in exon 9) in Korean population. Method and Result:CAD patients (n=146), confirmed by coronary angiography and healthy Korean adult volunteers (n=110) were genotyped for PvuII /HindIII RFLP and Ser447Ter mutation of the LPL gene by PCR-digestion method. Between two groups, the genotype frequency of these genetic variations was not different. But, the genetic variations showed different effect on lipid profile and body mass index (BMI) in the CAD group and in the control group. In the CAD group, P1 allele carriers showed higher total cholesterol (P1P1+P1P2:P2P2=216±51 mg/dl:198±38 mg/dl, p=0.039) and higher LDL cholesterol level (P1P1+P1P2:P2P2=143±46 mg/dl:126±36 mg/dl, p=0.047), and H1 allele carriers had lower Body mass index than non-carriers (23.8±2.3 kg/m:24.8±2.9 kg/m, p=0.047). In the control group, the Ser447Ter mutation carriers had higher HDL cholesterol level than non-carriers (59±10mg/dl versus 53±11mg/dl, p=0.049) and patients with P1 allele showed lower body mass index (P1P1+P1P2:P2P2=23.1±2.6 kg/m:24.5±2.6 kg/m, p=0.006). Conclusion:In Korean, PvuII/HindIII RFLP and Ser447Ter mutation was not associated with CAD, and they showed different effect on the lipid profile and on the body mass index according to the study group. These results 논문접수일:1999년 4월 6일 심사완료일:1999년 6월 9일 교신저자:김효수, 110-744 서울 종로구 연건동 28 서울대학교 의과대학 내과학교실 전화:(02) 760-2226·전송:(02) 766-8904 E-mail: hyosoo@plaza.snu.ac.kr

No Association Between α-Adducin 460 Polymorphism and Essential Hypertension in a Japanese Population

Many unknown genetic factors are involved in the pathogenesis of hypertension. Recently, the reverse genetic approach revealed that some genetic variants, such as angiotensinogen, lipoprotein lipase, and α-adducin gene polymorphisms, increase the risk for hypertension. Both in rat and human, the genetic predisposition to hypertension was confirmed only for angiotensinogen and α-adducin genes. Adducin is a membrane cytoskeletal protein, which is thought to regulate sodium transport. Abnormalities of membrane sodium transport in the kidney play an important role in hypertension. A recent report by Cusi et al showed that the Trp allele of α-adducin polymorphism (Gly 460 Trp) is associated with an increased risk of hypertension in whites, which led us to carry out a case-control study to examine whether the same association is observed in the Japanese population. We recruited 170 hypertensive and 194 normotensive Japanese subjects and compared the genotype distribution of α-adducin 460 polymorphism between cases and controls and between whites and Japanese. Trp allele frequency of controls in the Japanese subjects was twice as high as in the whites. However, no association was observed between α-adducin polymorphism and hypertension. Furthermore, α-adducin 460 polymorphism was not associated with any clinical characteristics. Accordingly, we concluded that α-adducin 460 polymorphism is not a major genetic risk for hypertension in Japanese people.

F085 Relations between lipoprotein lipase gene polymorphisms and insulin resistance in patiens with coronary heart disease

F085 Relations between lipoprotein lipase gene polymorphisms and insulin resistance in patiens with coronary heart disease

Lipoprotein Lipase Gene Polymorphisms: Associations With Coronary Artery Disease and Lipoprotein Levels in Japanese Population

Lipoprotein Lipase Gene Polymorphisms: Associations With Coronary Artery Disease and Lipoprotein Levels in Japanese Population

Lipoprotein lipase gene polymorphisms: associations with coronary artery disease and lipoprotein levels in Japanese population

Lipoprotein lipase gene polymorphisms: associations with coronary artery disease and lipoprotein levels in Japanese population

Lipoprotein lipase gene polymorphisms are predictors of risk of coronary artery disease and myocardial infarction

Lipoprotein lipase gene polymorphisms are predictors of risk of coronary artery disease and myocardial infarction

122 DNA polymorphisms of lipoprotein lipase gene in familial combined hyperlipidaemia

122 DNA polymorphisms of lipoprotein lipase gene in familial combined hyperlipidaemia