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      Association of CETP TaqI and APOE polymorphisms with type II diabetes mellitus in North Indians: a case control study

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      1 , 1 , 1 ,
      BMC Endocrine Disorders
      BioMed Central

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          Abstract

          Background

          Genetic variants of proteins involved in lipid metabolism may play an important role in determining the susceptibility for complications associated with type II diabetes mellitus (T2DM). Goal of the present study was to determine the association of cholesteryl ester transfer protein TaqI B, D442G, and APOE Hha I polymorphisms with T2DM and its complications.

          Methods

          Study subjects were 136 patients and 264 healthy controls. All polymorphisms were detected using PCR-RFLP and statistical analysis done with χ 2 test and ANOVA.

          Results

          Although CETP TaqI B polymorphism was not associated with the T2DM, yet B1B2 genotype was significantly (p = 0.028) associated with high risk of hypertension in diabetic patients (OR = 3.068, 95% CI 1.183–7.958). In North Indians D442G variation in CETP gene was found to be absent. Frequency of APOE HhaI polymorphism was also not different between patients and controls. In diabetic patients having neuropathy and retinopathy significantly different levels of total-cholesterol [(p = 0.001) and (p = 0.029) respectively] and LDL-cholesterol [(p = 0.001) and (p = 0.001) respectively] were observed when compared to patients with T2DM only. However, lipid levels did not show any correlation with the CETP TaqI B and APOE Hha I genetic polymorphisms.

          Conclusion

          CETP TaqI B and APOE HhaI polymorphism may not be associated with type II diabetes mellitus in North Indian population, however CETP TaqI B polymorphism may be associated with hypertension along with T2DM.

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          Most cited references56

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          Restriction isotyping of human apolipoprotein E by gene amplification and cleavage with HhaI.

          We have used restriction isotyping (restriction enzyme isoform genotyping) for rapid typing of common apolipoprotein E isoforms (E2, E3, E4). ApoE restriction isotyping used oligonucleotides to amplify apolipoprotein E gene sequences containing amino acid positions 112 and 158. The amplification products were digested with HhaI and subjected to electrophoresis on polyacrylamide gels. Each of the isoforms was distinguished by a unique combination of HhaI fragment sizes that enabled unambiguous typing of all homozygotic and heterozygotic combinations. HhaI cleaves at GCGC encoding 112arg (E4) and 158arg (E3, E4), but does not cut at GTGC encoding 112cys (E2, E3) and 158cys (E2).
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            Diagnosis and classification of diabetes mellitus.

            (2004)
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              Increased coronary heart disease in Japanese-American men with mutation in the cholesteryl ester transfer protein gene despite increased HDL levels.

              Plasma high density lipoprotein (HDL) levels are strongly genetically determined and show a general inverse relationship with coronary heart disease (CHD). The cholesteryl ester transfer protein (CETP) mediates the transfer of cholesteryl esters from HDL to other lipoproteins and is a key participant in the reverse transport of cholesterol from the periphery to the liver. A high prevalence of two different CETP gene mutations (D442G, 5.1%; intron 14G:A, 0.5%), was found in 3,469 men of Japanese ancestry in the Honolulu Heart Program and mutations were associated with decreased CETP (-35%) and increased HDL chol levels (+10% for D442G). However, the overall prevalence of definite CHD was 21% in men with mutations and 16% in men without mutations. The relative risk (RR) of CHD was 1.43 in men with mutations (P 60 mg/dl men with and without mutations had low CHD prevalence. Thus, genetic CETP deficiency appears to be an independent risk factor for CHD, primarily due to increased CHD prevalence in men with the D442G mutation and HDL cholesterol between 41 and 60 mg/dl. The findings suggest that both HDL concentration and the dynamics of cholesterol transport through HDL (i.e., reverse cholesterol transport) determine the anti-atherogenicity of the HDL fraction.
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                Author and article information

                Journal
                BMC Endocr Disord
                BMC Endocrine Disorders
                BioMed Central (London )
                1472-6823
                2005
                1 July 2005
                : 5
                : 7
                Affiliations
                [1 ]Department of Genetics, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow-226014 India
                Article
                1472-6823-5-7
                10.1186/1472-6823-5-7
                1187885
                15992403
                243f909a-9c5f-4ca7-b923-50ad43c16184
                Copyright © 2005 Dixit et al; licensee BioMed Central Ltd.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 27 January 2005
                : 1 July 2005
                Categories
                Research Article

                Endocrinology & Diabetes
                Endocrinology & Diabetes

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