P-7：Angiotensin converting enzyme gene polymorphism and diabetic nephropathy

in Filipino type 2 diabetes mellitus patients

Elizabeth Paz-Pacheco, MD^*;   Eva Maria C Cutiongco, MD^**;   Gabriel V Jasul Jr, MD^*;

Ma Cecille A Cruz, MD^*

^*   Section of Endocrinology, Diabetes, and Metabolism,; Department of Medicine;   College of Medicine; University of the Philippines Manila

^**  Institute of Human Genetics, National Institutes of Health, University of the Philippines Manila

ABSTRACT

Background.   Angiotensin converting enzyme (ACE) gene polymorphism plays a major role in genetic susceptibility to diabetic nephropathy in Japanese, Taiwanese and South Indian patients. ^4-6

Objectives. We aim to determine the frequencies of ACE gene polymorphism among Filipino type 2 diabetic patients and normal controls, and to identify the clinical characteristics of these patients according to ACE genotype.

Methods. We will extract DNA from peripheral blood obtained from 50 type 2 diabetic patients with nephropathy, 50 type 2 diabetic patients without nephropathy, and 50 normal controls. We will subject these samples to polymerase chain reaction, restriction enzyme digestion, and gel electrophoresis techniques.

Data Analysis.   We will use independent T-tests and Fisher’s exact test to compare the clinical characteristics of the different ACE genotypes.

Clinical Implications.   This study will provide preliminary data on the pattern of ACE gene polymorphism among Filipino type 2 diabetes patients. Additional evidence supporting direct association of ACE gene polymorphism in Filipino patients with diabetic nephropathy may help in establishing ACE genotype as a prognostic indicator for diabetes and renal disease.

BACKGROUND

q       Genetic susceptibility plays a major role in the pathogenesis of diabetic nephropathy. ^1-3

q       The angiotensin converting enzyme (ACE) gene is viewed as one of the important factors in the development of diabetic nephropathy. ^4-5

q       A significant association of ACE gene polymorphism and diabetic nephropathy was found in Japanese, Taiwanese and South Indian diabetic patients.^1-3

q       To date, there is no available data on the ACE genotypes of Filipino diabetic patients.

OBJECTIVES

This study aims to

q       To determine the frequency distribution of ACE genotypes in Filipino diabetic patients with and without nephropathy.

q       To identify the clinical characteristics of Filipino diabetic patients according to ACE genotype.

MATERIALS AND METHODS

Patients recruited from the Diabetes Clinic of a tertiary government hospital

Prior diagnosis of Type 2 diabetes mellitus based on any of the American Diabetes Association criteria established

a.        fasting plasma glucose ³ 126 mg/dl on at least 2 occasions; OR

b.       casual plasma glucose ³ 200 mg/dl in the presence of symptoms such as polyuria, polydipsia, weight loss;  OR

c.        plasma glucose ³ 200 mg/dl  2 hours after a 75 gram glucose challenge

Non-diabetic subjects recruited should fulfill all of the criteria :

a.        aged ³ 60 years; AND

b.       without a personal history of diabetes mellitus;  AND

c.          without a parent, offspring or sibling with diabetes mellitus

Control prospects screened for the following inclusion criteria with a 75-gram

oral glucose tolerance test:

d.       FPG < 110 mg/dl;  AND

e.        2-hour plasma glucose < 140 mg/dl

Independent t-test and Fisher’s exact test from Intercooled Stata 6.0 utilized for statistical analysis

DNA ANALYSIS

References:

1. American Diabetes Association. Nephropathy in diabetes. Diabetes Care 2004 Jan, 27(Suppl1):S79-S83
2. Seaquist ER, Goetz FC, Rich S et al. Familial clustering of diabetic kidney disease: evidence of genetic susceptibility to diabetic nephropathy. N Engl J Med 1989; 320:1161-1165
3. Borch-Johnsen K, Nørgaard K, Hommel E et al. Is diabetic nephropathy an inherited complication? Kidney Int 1992; 41:719-722
4. Tarnow L, Gluud C, Parving H. Diabetic nephropathy and the insertion/deletion polymorphism of the angiotensin-converting enzyme gene. Nephrol Dial Transplant 1998; 13:1125-1130
5. Hsieh M, Lin S, Hsieh T et al. Increased frequency of angiotensin-converting enzyme DD genotype in patients with type 2 diabetes in Taiwan. Nephrol Dial Transplant 2000; 15:1008-1013
6. Viswanathan V, Zhu Y, Bala K et al. Association between ACE gene polymorphism and diabetic nephropathy in South Indian patients. J Pancreas 2001; 2(2):83-87