THE GENETICS OF LIPOPROTEIN

METABOLISM AND HEART DISEASE

E. Shyong Tai
Singapore General Hospital, Singapore

dibawakan oleh :
dr. Indrawaty Alimuddin / C175172005
 Blood lipid Modifiable risc
levels factors for CAD

High levels of ↑ CAD

LDL-C
1. Risk of CAD : Indian > Malay >
Chinese
2. APOE4 allele was highest in Malays,
the ethnic group with a higher LDL-C
concentration
3. B2 allele was highest in Indians, the
ethnic group with the lowest HDL-C
concentration.
 CAD

Changes in level
or function of
protein
the ɛ4 contains an arginine

SNPs Codon
112
Encoded by APOE
genetic locus locus
Codon
158
The ɛ2 allele contains a cysteine21
 D
E
T
E
R
the effect of M
I an individual’s
diet on blood N
E
genetic
lipid levels D
makeup
B
Y
 • T polymorphism at the hepatic lipase (LIPC) locus/ T allele is
associated with elevated serum HDL-C concentration in
many studies

• In those with the TT genotype, high dietary fat intake was

The associated with low HDL-C concentration whereas in those
Framingham with the CC genotype, the opposite was true.
offspring

• TT genotype may identify a group of individuals who are

maladapted to a high-fat diet in relation to cardiovascular
disease risk.

• that a high-fat diet had an adverse effect on the serum lipid

profile in the form of hypertriglyc-eridemia in all three ethnic
Singapore groups in those with the TT genotype
 Diet/nutrient

Genetic Chronic Environmental

markers
disease exposures
 EXAMPLE

polymorphisms at the
peroxisome proliferator-
activated receptor-a
• substitution • results in a
of saturated (PPAR-a) locus interact
• unsaturated decrease in
fat in the serum HDL- with dietary
fat polyunsaturated fatty
diet C concen-
tration acid intake to determine
HDL-C concentrations in
Chinese women
GENE-ENVIRONMENT INTERACTIONS
AND THE DIABETES EPIDEMIC IN
INDIA

V. Mohan, V. Sudha, G. Radhika, V. Radha, M. Rema, R. Deepa

Madras Diabetes Research Foundation and Dr. Mohan’s Diabetes

Specialities Centre, Gopalapuram, Chennai, India
 W H O

2000 2030

The Top Three • 366

• 171 1. India million
million 2. China had
3. USA diabetes
 The Chennai Urban Population
Study ( The CUPS )
• 1,262 subjects ( aged over 20 yrs )
• underwent a glucose tolerance test
• were categorized as having normal
glucose tolerance, impaired glucose
tolerance (IGT) or diabetes
• The overall prevalence of diabetes
was 12%
• 91 subjects (7.2%) with diabetes
and 61 (4.8%) with undiagnosed
diabetes
• 74 (5.9%) subjects were detected to
have IGT
• The prevalence of diabetes and the
metabolic abnormalities among the
high-income group was twofold
higher than that observed in the
middle-income group (12.4 vs.
6.5%)
The Chennai Urban Rural
Epidemiology Study ( The CURES )
• The total sample size of 26,001
individuals was selected from these
46 wards.
• All men and women 20 years of age
• Fasting capillary blood glucose was
determined using a One Touch
Basic glucose meter
• were categorized as having normal
fasting glucose, impaired fasting
glucose or diabetes
• also classified as ‘known diabetic
subjects’ if they stated that they had
diabetes and were on treatment
• . In phase 2 of the CURES, all the
known diabetic subjects (n 1,529)
were invited to the center for
detailed studies on vascular compli-
cations
• In phase 3, every tenth study
subject in phase 1 was invited to the
cen-ter for more detailed studies
WHY THE DIABETES EPIDEMIC IN INDIA?

point to the role of both

Still unclear genetic and
environmental factors
 THE CUPS
The prevalence of diabetes was
higher among subjects who had
a positive family history of
diabetes (18.2%) compared to
subjects without a family history
of diabetes (10.6%, p 0.0015)
When subjects with diabetes
and IGT were grouped as
glucose intolerance, the
prevalence of glucose
intolerance among subjects
whose parents were both
diabetic (55%) was higher than
those with one diabetic parent
(22.1%, p 0.005), which in turn
was higher than the prevalence
among those with no parental
history of diabetes (15.6%, p
0.0001)
TERIMA KASIH