Genetics and Environmental

Interaction

dr Ruswana Anwar, SpOG

dr Wiryawan Permadi, SpOG(K)
Introduction
 Most normal trait(e.g.,behavior) and
most common diseases of middle life
exhibit multifactorial inheritance, they
are due to a combination of genetic and
nongenetic factor.
 Most common isolated congenital
anomalies also are multifactorial
Pharmacogenetics :
influence of genes on the response to drug
therapy
 Genes affecting drug metabolism
1. Acetylation : genetic polymorphism
- isoniazid,side effect develop
2. Cytochrome P450-dependent enzyme
system
- poor metabolizers : propanolol
3. Genetic polymorphism in the enzyme
alcohol dehydrogenase
Pharmacologic effect of drugs
on certain genetic disease
1. Glucose-6-phosphate dehydrogenase
(G6PD) deficiency
- rapid hemolysis to
sulfonamide/antimalarial agent
- an X-linked recessive trait
2. Malignant hyperthermia
- triggered by anesthetic agent,
halothane
- genetically heterogeneous : 17,19
- muscle spasm, hyperthermia, acidosis
3. Human leucocyte antigen
4. Succinylcholine sensitivity
 Clinical concerns in pharmacogenetics
- family history
- undertake appropriate investigations, avoid
the use of such drugs
- drug metabolism is determined in large part
by genetic factor
- unusual adverse reactions may reflect the
presence of genetic allele
- certain drug may be teratogenic
Multifactorial inheritance
 Multifactorial : combination of many
genetic and nongenetic factors
- both a familial nature and an
environmental dependence
- genetics predisposition inherited from
both parent
- the genes and environmental factors
may vary among different individual
Factor that influence the recurrence risk
for multifactorial disorder
 a.The recurrence risk is higher if more than
one close relative is affected
-cleft lip
 b.The recurrence risk is higher in the
relatives of an affected individual of the less
frequently involved sex
-pyloric stenosis
 c.The recurrence risk is higher in relative of
more severely affected probands
Multifactorial inheritance is a
diagnosis of exclusion
 a.The clinical features of multifactorial
disorder rarely distinguish it from similar
lesions that have another cause
- chromosome abnormalities,monogenic
disorders or teratogenic environment
 b.Typically occur in patient who do not have
embryologically unrelated birth defect
 Environmental triggers have the
greatest chance of causing disease in
individuals with existing genetic
predisposition
- identification
- manipulation
- disease prevention through
manipulation of nongenetic factor
 Twin studies
 Monozygotic(MZ) twin have all of their genes in
common
 Familial traits are not necessarily genetics
 If one of pair of MZ has a multifactorial disease,
the chance that the second twin is also affected
is less than 100%
 Advantage of twin studies : provide powerful
method of distinguishing caused of disease
caused by combination genetic and nongenetic
 Limitation : biased sampling: small sample