This Article Abstract Full Text (PDF) Submit a related Letter to the Editor Purchase Article View Shopping Cart Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Durlach, A. Articles by Durlach, V. Search for Related Content PubMed PubMed Citation Articles by Durlach, A. Articles by Durlach, V.

Sex-Dependent Association of a Genetic Polymorphism of Cholesteryl Ester Transfer Protein with High-Density Lipoprotein Cholesterol and Macrovascular Pathology in Type II Diabetic Patients

Institut Pol Bouin (A.D., C.C.), Hôpital Maison Blanche, Centre Hospitalo-Universitaire, 51092 Reims; Laboratoire de Métabolisme des Lipides (A.G.-G.), Hôpital de l’Antiquaille and CNRS UPRESA 5014, 69005 Lyon; Service d’Endocrinologie (V.D.), Maladies Métabolique et de Médecine Interne, Hôpital Robert Debré, Centre Hospitalo-Universitaire, 51092 Reims, France

Address all correspondence and requests for reprints to: Dr. Anne Durlach, Institut Pol Bouin, Hôpital Maison Blanche, Centre Hospitalo-Universitaire, 51092 Reims, France.

	Abstract

Top Abstract Introduction Patients and Methods Results Discussion References

 
Cholesterol ester transfer protein (CETP) is a key regulating factor of lipid metabolism, and the polymorphism of its gene may be a candidate for modulating the lipid parameters in type 2 diabetic subjects. In a group of 406 type 2 diabetic patients aged 59.5 ± 10.8 y, with a body mass index of 28.9 ± 5.3 kg/m² and HbA1c = 8.2 ± 1.9%, we studied the B polymorphism at the CETP locus detectable with the restriction enzyme TaqI. Patients were separated into groups, 231 males (78 B1B1, 108 B1B2, 45 B2B2) and 175 females (48 B1B1, 94 B1B2, 33 B2B2), and compared on the basis of their lipid parameters (total cholesterol, triglycerides, high-density lipoprotein-cholesterol (HDL-C), ApoA1 ApoB, and low-density lipoprotein-cholesterol), their micro and macrovascular complications. HDL-C was significantly higher in man with the B2B2 genotype (respectively, 1.31 ± 0.44 mmol/L vs. 1.13 ± 0.32 mmol/L, P < 0.05), together with a lower incidence of coronary heart disease (9 vs. 25% for B1B1 and B1B2 together). Women displayed a higher HDL-C than men and a equally high incidence of coronary heart disease in B2 homozygotes as in other genotypes (26 vs. 27%). Thus, in type 2 diabetic patients, Taq1b polymorphism seems to exert a modulating role in males only. This may contribute to the loss of macrovascular protection in type 2 diabetic females.

	Introduction

Top Abstract Introduction Patients and Methods Results Discussion References

 
NONINSULIN-dependent diabetic (NIDDM) patients are at high risk of early atherosclerosis, particularly of coronary heart disease (CHD) (1). This increased risk can be partly accounted for by the lipoprotein disorders linked to insulin resistance: elevated very low-density lipoprotein (VLDL), triglycerides (TGs), and cholesterol together with low high-density lipoprotein (HDL) cholesterol (2).

In this perspective, parameters modulating the concentrations of TG and cholesterol are of particular interest in NIDDM patients. Among these, cholesterol ester (CE) transfer protein (CETP) facilitates the exchange of CEs in HDL with TGs in VLDL and presumably plays a key role in cholesterol homeostasis (3) by efficiently addressing CEs from HDL to the liver via the receptors of the LDL-receptor family. When, as in NIDDM, VLDL or HDL metabolism are perturbed, CETP can, however, contribute to the formation of atherogenic apoB-containing particles, enriched with CE and deplete the CE stores of HDL. A frequent Taq1B polymorphism of the CETP gene is associated with variability in CETP activity and mass, as well as in HDL-C concentrations (4, 5, 6), although it is not clear that there is a causal link between the two (6, 7, 8). The B2 allele (no restriction site) is associated with low CETP activity, high cholesterol concentrations, and with a reduction of cardiovascular risk under the effect of alcohol. This suggests that genetic variability of the CETP gene is likely to also have an impact on the lipid profile of NIDDM patients, but reports on the subject are few (8, 9). We have addressed the issue in a series of 406 unrelated male and female NIDDM patients explored for micro- and macrovascular complications, with particular emphasis on gender effects because it is known that hypertriglyceridemia enhances the transfer activity of CETP (10) and constitutes a specific cardiovascular risk factor for female diabetic patients (11, 12).

	Patients and Methods

Top Abstract Introduction Patients and Methods Results Discussion References

 
The study population comprised 406 unrelated French patients with NIDDM (231 men and 175 women), aged 59.5 ± 10.8 yr (27–83 yr), attending the Diabetes Center in Reims who volunteered for the study. The protocol was approved by the local ethics committee. The criteria for noninsulin-dependent diabetes were those defined by the National Diabetes Data Group (13). Mean duration of diabetes was 11.7 ± 7.7 yr. Mean body mass index (BMI) was 28.9 ± 5.3 kg/m². Arterial blood pressure was measured at the right arm after a 10-min rest in the supine position. Hypertension was diagnosed when systolic pressure was greater than or equal to 160 mm Hg or diastolic pressure was greater than or equal to 95 mm Hg or if an antihypertensive treatment had been prescribed. Albuminuria was defined as a urinary albumin excretion rate between 20 and 200 µg/min or 30–300 mg/24 h.

The patients were treated by diet and/or antidiabetic drugs (biguanids and/or sulfonylurea). Eighty-seven patients were under lipid-lowering therapy: 20 with statins and 67 with fibrates. Nineteen percent of the patients were smokers. Most women were postmenauposal, and none received hormonal replacement therapy.

Vascular pathologies

CHD was diagnosed on the basis of previous myocardial infarction and/or angina, electric signs on resting electrocardiogram. Arteriopathy was diagnosed on the basis of intermittent claudication or absence of peripheral pulse confirmed by ultrasonography. Renal function was assessed by serum creatinine (reference values <90 µmol/L), presence of microalbuminuria (30–300 mg/24 h), or overt proteinuria (>300 mg/24 h). Retinopathy was diagnosed by fundoscopy and angiography.

Plasma lipids and lipoproteins

Fasting blood glucose, cholesterol, TGs, and creatinine were measured on a BM/Hitachi 747 analyzer (Boehringer Mannheim, Meylan, France), and apolipoprotein A1 and B and urinary albumin were measured on an Array 360 analyzer (Beckman, Gagny, France) according to the manufacturers’ instructions. HbA1c was assayed by high-pressure liquid chromatography on a Diamat analyzer (Bio-Rad, Ivry-sur-Seine, France), according to the recommendations of the Société Française de Biologie Clinique. HDL-cholesterol (HDL-C) was determined after dextran sulfate/MgCl2 precipitation.

Genetic analysis

Genomic DNA was extracted from white blood cells by phenol. Primers were synthesized to amplify the intron 1 region of chromosome 16 (7). Each amplification was performed using 300 ng genomic DNA containing 10 pmol of each primer, and 1 U of Taq polymerase (Bioprobe Systems, Montrevi P.ss. Bois, France), with 10 mM Tris-HCl, 50 mM KCl, 1.5 mM MgCl2, and 200 µM each dNTP, and consisted of 30 cycles of 30 sec of denaturation at 94°C, 30 sec of annealing at 60°C, and 1 min of elongation at 72°C. To detect the CETP/Taq1 polymorphism, 10-µl aliquots were digested with 5 U TaqI at 65°C for 3 h and the digests were analyzed on 2% agarose gels.

Statistical analysis

All values are expressed as mean ± SD, median and range. TG and Lp(a) distributions being positively skewed, the values were transformed to their natural logarithm. Statistical calculations were performed first for all subjects, then separately for males and females. When appropriate, comparisons between two groups were performed by ² tests for independent qualitative samples. Between genotypes the mean values of continuous parameters were compared by use of the Wilcoxon test or by analysis of variance (ANOVA). Correlations were investigated using Pearson’s correlation coefficient.

	Results

Top Abstract Introduction Patients and Methods Results Discussion References

 
Clinical characteristics of the patients are reported in Table 1. No differences in age, duration of diabetes, glycosylated hemoglobin, fasting blood glucose or BMI could be evidenced between males and females. Among lipid parameters, only HDL-C and apo Al were, as expected, significantly higher in women (P < 0.0001). The proportion of patients treated by lipid-lowering agents was the same in all genotypic groups. HDL-C concentrations did not differ significantly in subjects treated with fibrates or statins, compared with those who were not treated. The allele frequency of the Taq1B restriction site was similar and in Hardy-Weinberg equilibrium, with respective frequencies for B1 of 0.57 in men and 0.54 in women, not significantly different from those reported in other nondiabetic populations (7, 14, 15). Apart from HDL-C and apo Al, none of the parameters considered displayed any differences linked to genotype, whether in males or in females.

Although HDL-C concentrations were higher in B2B2 than in B1B1 homozygotes (Table 2; P < 0.05), the effect of Taq1B polymorphism did not reach significance when evaluated by ANOVA in the total population (F = 2.010, P = 0.1353). When significance was assessed separately for the two sexes, however, Taq1B polymorphism was found to affect HDL-C significantly in males (F = 3.640, P = 0.028) but not in females (F = 0.947, P = 0.390) (Table 2). As a result, the difference in HDL-C between sexes, reconsidered on the basis of Taq1B genotype, was found to be significant at the P < 0.0001 and P < 0.0005 levels, respectively, in B1B1 and B1B2 subjects because females bearing the B1 allele failed to display the lower HDL-C found in males. It was not significant in B2B2 homozygotes because males had elevated concentrations of HDL linked to the B2 allele (Table 2). These effects were reflected in apoAl concentrations, which were influenced by genotype in males (B1B1, 1.26 ± 0.21; B2B2, 1.35 ± 0.21 g/L, P < 0.02) but not in females. The differences between sexes were significant only in individuals with the B1B1 genotype, in accordance with the HDL-C data. Interaction between polymorphism and sex did not quite reach significance (F = 1.856, P = 0.1577).

The incidence of macro- or microvascular complications was not affected by either type of lipid-lowering treatment. The association of genotype with the incidence of macro- and microvascular complications was tested by the ² test. The interaction was far from significant for nephropathy or for retinopathy, but approached significance for coronaropathy (P = 0.09) and arteriopathy (P = 0.122). The ECTIM study having revealed that alcohol intake significantly protects against myocardial infarction, only those individuals with the B2B2 genotype (7) we felt justified in comparing homozygotes for the B2 allele with the remainder of the population, taking sex into account. Table 3 shows that male patients with the B2B2 phenotype exhibited significantly less coronaropathy than others, whereas the figures for arteriopathies did not quite reach significance. Curiously, this was a true protective effect, reducing the proportion of cases even with respect to females. It should be noted, incidentally, that in this population TG concentrations did not differ between patients with or without vascular involvement (results not shown). Because the Taq1B polymorphism of the CETP gene also has an effect in males only, we compared HDL-C concentrations in the two phenotypic populations (Table 3) to show, as expected, significantly higher levels in male individuals with the B2B2 phenotype than in their B1B2 or B1B1 counterparts. No differences could be found, however, between the HDL-C concentrations of patients suffering or not from vascular pathologies. In males with or without coronary damage, in particular, HDL-Cs were strictly identical (1.19 ± 0.34 and 1.19 ± 0.35 mmol/L, respectively).

	Discussion

Top Abstract Introduction Patients and Methods Results Discussion References

In the population of 406 NIDDM subjects presented here, we found the Taq1B polymorphism of the CETP gene to have an impact on HDL-C concentrations in male subjects only, females displaying equally high concentrations independent of genotype. Insofar as their is a link between HDL-C and CETP activity, it thus seems to be overcome by the determinant factors of high HDL in the female sex. Anterior studies have not explored the possibility for a sex-difference in response to polymorphism, but this observation adds to the already large corpus of data indicating that the relationship between HDL-C and CETP activity is not a direct one. In nondiabetic subjects, one might speculate that the smaller pool of VLDL associated with rapid lipolysis in females might restrict transfer of CE out of HDL while contributing larger amounts of PL to HDL surface and limit the effects of high CETP activity linked to the B1B1 genotype. In this study, however, as in others concerning NIDDM patients, TG concentrations were not lower in females as in males, and most of the females postmenopausal with no hormonal replacement therapy so that the cause must be sought elsewhere. Different levels or localizations of CETP expression are a possibility: CETP is expressed in adipose tissue (23), where it promotes selective uptake of HDL-C (24). Small, lipid-poor adipocytes of the type encountered in abdominal fat express higher levels of CETP messengerRNA (25) and may play a predominant role in male subjects.

The presence of the B2 allele seems to increase the sensitivity for modulation by environmental factors. Thus, generally speaking, alcohol intake increases HDL-C and decreases CETP, but, in fact, it only does so in bearers of the B2 allele (7). As a result, the risk of myocardial infarction is significantly lessened only in drinkers with the B2B2 genotype. Besides, this common DNA variant seems to be a good predictor of wether nondiabetic men with CHD will benefit from treatment with pravastatin to delay the progression of atherosclerosis (26). This polymorphism is, therefore, a likely candidate for predisposition (or protection) with respect to that part of cardiovascular risk related to CE transfer and HDL metabolism. A study, bearing on the same type of subjects as in this report (9) but with a larger proportion of males, failed to evidence any association between CETP Taq1B polymorphism and plasma lipids or lipoproteins. It did, however, conclude to a lower incidence of macroangiopathic involvement in B2 homozygotes, suggestive of some protective relationship.

In the population of 406 NIDDM subjects presented here, B2 homozygotes were, indeed, found to be protected against coronary damage, provided they were males. Although they did display significantly higher levels of HDL-C than males with other genotypes, their concentrations of HDL-C were unrelated to the incidence of macroangiopathy. Moreover, HDL-C concentrations were no higher than in females with the same phenotype who were not protected. In diabetic patients, the negative link between HDL concentrations and incidence of vascular pathology seems to be weaker than in other populations and, in several studies, was observed only in women (27, 28). In this population, however, the relation did not reach the level of statistical significance even in women, confirming the low predictive value of HDL in NIDDM patients and suggesting that the pathogeny of obstructive vascular disease might be quite different in NIDDM from what it is in other types of pathologies. Dysfunctionnal HDL?

In the absence of CETP mass or activity determinations, it cannot be evaluated whether the development of macrovascular complications is at all related to the level of CETP expression, but it is quite evident that, in the present case, protection is not mediated by an effect on fasting levels of HDL concentrations. Among other likely possibilities are: 1) linkage disequilibrium with another gene critically involved in vascular protection; 2) a difference in postprandial evolution of CETP and/or HDL; or 3) a distinct effect on TG-rich lipoprotein metabolism.

Our results, thus, indicate that in women patients with NIDDM the Taq1B polymorphism of CETP plays a minor role, if any, in the determinism of HDL-C and that their resistance to the lowering effect of the B1 allele on HDL-C concentrations is not associated with a corresponding resistance to vascular pathologies. In men, by contrast, the B2 allele corresponds to a lesser incidence of vascular pathology. Although HDL-C concentrations are also elevated, they bear no relation to vascular involvement. This lends credence to the hypothesis that CETP Taq1B polymorphism is related to vascular pathology, independent of its likely effect on plasma lipid transfers.

	Acknowledgments

 
Prof. Philippe Moulin is gratefully acknowledged for critical review of the manuscript and helpful discussions.

Received January 20, 1999.

Revised May 26, 1999.

Accepted July 6, 1999.

	References

Top Abstract Introduction Patients and Methods Results Discussion References

 

1. Pyörälä K, Laakso M, Uusitupa M. 1987 Diabetes and atherosclerosis: an epidemiological view. Diabetes Metab Rev. 3:463–524.[Medline]
2. Dunn FL. 1990 Hyperlipidemia in diabetes mellitus. Diabetes Metab Rev. 6:47–61.[Medline]
3. Albers JJ, Tollefson JH, Chen CH, Steinmetz A. 1984 Isolation and characterization of human plasma transfer proteins. Arteriosclerosis. 4:49–58.[Abstract/Free Full Text]
4. Kondo I, Berg K, Drayna D, Lawn R. 1989 DNA polymorphism at the locus for human cholesteryl ester transfer protein (CETP) is associated with high-density lipoprotein cholesterol and apolipoprotein levels. Clin Genet. 35:49–56.[Medline]
5. Freeman DJ, Packard CJ, Shepherd J, Gaffney D. 1990 Polymorphisms in the gene coding for cholesteryl ester protein are related to plasma high-density lipoprotein cholesterol and transfer protein activity. Clin Sci. 79:575–581.[Medline]
6. McPherson R, Grundy SM, Guerra R, Cohen JC. 1996 Allelic variation in the gene encoding the cholesteryl ester transfer protein is associated with variation in the plasma concentrations of cholesteryl ester transfer protein. J Lipid Res. 37:1743–1748.[Abstract]
7. Fumeron F, Betoulle D, Luc G, et al. 1995 Alcohol intake modulates the effect of a polymorphism of the cholesteryl ester transfer protein gene on plasma high-density lipoprotein and the risk of myocardial infarction. J Clin Invest. 96:1664–1671.
8. Ukkola O, Savolainen MJ, Salmela PI, von Dichoff K, Kesäniemi YA. 1994 DNA polymorphisms at the locus for human cholesteryl ester transfer protein (CETP) are associated with macro- and microangiopathy in non-insulin-dependent diabetes mellitus. Clin Genet. 46:217–227.[Medline]
9. Bernard S, Moulin P, Lagrost L, et al. 1998 Association between plasma HDL-cholesterol concentration and Taq1B CETP gene polymorphism in non-insulin-dependent diabetes mellitus. J Lipid Res. 39:59–65.[Abstract/Free Full Text]
10. Mann CJ, Yen FT, Grant AM, Bihain B. 1991 Mechanism of plasma cholesteryl ester transfer in hypertriglyceridemia. J Clin Invest. 88:2059–2066.
11. West KM, Ahuja MM, Bennett PH. 1983 The role of circulating glucose and triglyceride concentrations and the interactions with other "risk factors" as determinants of arterial disease in nine diabetic population samples from the WHO multinational study. Diabetes Care. 6:361–369.[Abstract]
12. Fontbonne A, Eschwège E, Cambien F. 1989 Hypertriglyceridemia as a risk factor of coronary heart disease mortality in subjects with impaired glucose tolerance or diabetes: results from the 11-year follow-up of the Paris prospective study. Diabetologia. 32:300–304.[CrossRef][Medline]
13. National Diabetes Data Group. 1979 Classification and diagnosis of diabetes mellitus and other categories of glucose tolerance. 28:1039–1057.
14. Drayna D, Lawn R. 1987 Multiple RFLPs at the human cholesteryl ester transfer protein (CETP) locus. Nucleic Acids Res. 15:4698.[Free Full Text]
15. Tenkanen H, Koskinen P, Aalto-Setälä K, et al. 1991 Polymorphisms of the gene encoding cholesterol ester transfer protein and serum lipoprotein levels in subjects with and without coronary heart disease. Hum Genet. 84:574–578.
16. Biesbroeck RC, Albers JJ, Wahl PW, Weinberg CR, Bassett ML, Bierman EL. 1982 Abnormal composition of high-density lipoproteins in non-insulin-dependent diabetes. Diabetes. 31:126–131.[Medline]
17. Bagdade JD, Buchanan WE, Kuusi T, Taskinen MR. 1990 Persistent abnormalities in lipoprotein composition in noninsulin-dependent diabetes after intensive insulin therapy. Arteriosclerosis. 10:232–239.[Abstract/Free Full Text]
18. Kasim SE, Tseng K, Jen KLC, Khilnani S. 1987 Significance of hepatic triglyceride lipase activity in the regulation of serum high-density lipoproteins in type II diabetes mellitus. J Clin Endocrinol Metab. 65:183–187.[Abstract]
19. Syvänne M, Ahola M, Lahdenperä S, et al. 1993 High-density lipoprotein subfractions in non-insulin-dependent diabetes mellitus and coronary heart disease. J Lipid Res. 6:573–582.
20. Bagdade JD, Lane JT, Subbaiah PV, Otto ME, Ritter MC. 1993 Accelerated cholesteryl ester transfer in non-insulin-dependent diabetes mellitus. Atherosclerosis. 104:69–77.[CrossRef][Medline]
21. Durlach V, Attia N, Zahouani A, Leutenegger M, Girard-Globa A. 1995 Postprandial cholesteryl ester transfer and high-density lipoprotein composition in normotriglyceridemic non-insulin-dependent patients. Atherosclerosis. 20:155–165.
22. Jiang XC, Moulin P, Quinet E, et al. 1991 Mammalian adipose tissue and muscle are major sources of lipid transfer protein. J Biol Chem. 266:4631–4639.[Abstract/Free Full Text]
23. Dullart RPF, Hoogenberg K, Riemens SC, et al. 1997 Cholesterol ester transfer protein gene polymorphism is a markor of HDL-cholesteroland of lipoprotein response to a lipid lowering diet in type 1. Diabetes. 46:2082–2087.[Abstract]
24. Benoist F, Lau P, McDonnell M, Doelle H, Milne R, McPherson R. 1997 Cholesteryl ester transfer protein mediates selective uptake of high density lipoprotein cholesterol esters by human adipose tissue. J Biol Chem. 272:23572–23577.[Abstract/Free Full Text]
25. Radeau T, Lau P, Robb M, McDonnell M, Ailhaud G, McPherson R. 1995 Cholesteryl ester transfer protein (CETP) mRNA abundance in human adipose tissue: relationship to cell size and membrane cholesterol content. J Lipid Res. 36:2552–2561.[Abstract]
26. Kuivenhoven JA, Wouter Jukema J, Zwinderman AH, et al. 1998 The role of a common varaint of the cholesteryl ester transfer protein gene in the progression of coronary atherosclerosis. N Engl J Med. 338:86–93.[Abstract/Free Full Text]
27. Reckless JPD, Betteridge DJ, Wu P, Payne B, Galton DJ. 1978 High-density and low-density lipoproteins and prevalence of vascular disease in diabetes mellitus. Br Med J. 1:883–886.
28. Seviour PW, Teal TK, Richmond W, Elkeles RS. 1988 Serum lipids, lipoproteins and macrovascular disease in noninsulin-dependent diabetics: a possible new approach to prevention. Diabetic Med. 5:166–171.[Medline]

This article has been cited by other articles:

				I. Porchay-Balderelli, F. Pean, N. Bellili, R. Jaziri, M. Marre, F. Fumeron, and for the DIABHYCAR Study Group The CETP TaqIB Polymorphism Is Associated With the Risk of Sudden Death in Type 2 Diabetic Patients Diabetes Care, November 1, 2007; 30(11): 2863 - 2867. [Abstract] [Full Text] [PDF]

				N. A. Patsopoulos, A. Tatsioni, and J. P. A. Ioannidis Claims of Sex Differences: An Empirical Assessment in Genetic Associations JAMA, August 22, 2007; 298(8): 880 - 893. [Abstract] [Full Text] [PDF]

				J. E. Kanter, F. Johansson, R. C. LeBoeuf, and K. E. Bornfeldt Do Glucose and Lipids Exert Independent Effects on Atherosclerotic Lesion Initiation or Progression to Advanced Plaques? Circ. Res., March 30, 2007; 100(6): 769 - 781. [Abstract] [Full Text] [PDF]

				S. M. Boekholdt and J. F. Thompson Natural genetic variation as a tool in understanding the role of CETP in lipid levels and disease J. Lipid Res., July 1, 2003; 44(6): 1080 - 1093. [Abstract] [Full Text] [PDF]

				F. V. van Venrooij, R. P. Stolk, J.-D. Banga, T. P. Sijmonsma, A. van Tol, D. W. Erkelens, and G. M. Dallinga-Thie Common Cholesteryl Ester Transfer Protein Gene Polymorphisms and the Effect of Atorvastatin Therapy in Type 2 Diabetes Diabetes Care, April 1, 2003; 26(4): 1216 - 1223. [Abstract] [Full Text] [PDF]

				M.C. Mahaney, L. Almasy, D.L. Rainwater, J.L. VandeBerg, S.A. Cole, J.E. Hixson, J. Blangero, and J.W. MacCluer A Quantitative Trait Locus on Chromosome 16q Influences Variation in Plasma HDL-C Levels in Mexican Americans Arterioscler. Thromb. Vasc. Biol., February 1, 2003; 23(2): 339 - 345. [Abstract] [Full Text] [PDF]

				L. Iacoviello, E. Ciccarone, and M. B. Donati Review: The genetics of macrovascular disease in diabetes The British Journal of Diabetes & Vascular Disease, September 1, 2002; 2(5): 364 - 368. [Abstract] [PDF]

				I. Kawasaki, H. Tahara, M. Emoto, T. Shoji, and Y. Nishizawa Relationship Between TaqIB Cholesteryl Ester Transfer Protein Gene Polymorphism and Macrovascular Complications in Japanese Patients With Type 2 Diabetes Diabetes, March 1, 2002; 51(3): 871 - 874. [Abstract] [Full Text] [PDF]

This Article Abstract Full Text (PDF) Submit a related Letter to the Editor Purchase Article View Shopping Cart Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Durlach, A. Articles by Durlach, V. Search for Related Content PubMed PubMed Citation Articles by Durlach, A. Articles by Durlach, V.