1. LETTER TO THE EDITOR
Parent-of-origin effect: A hint from vitiligo
epidemiology
[*Correction added after online publication 25 February 2011: Spelling of ‘epidemiology’ corrected]
Dear Editor,
Vitiligo is a commonly observed complex depig-
mentation skin disorder that affects 0.1–2% of the
population worldwide, has both clinical and genetic
heterogeneity, and follows a non-Mendelian pattern
of transmission, suggestive of polygenic inheri-
tance.1
Estimation of recurrence risk from the epi-
demiological data of the affected families helps in
identification of a relative contribution of a genetic
component in the causation of this disease. The
objective of the present paper is to estimate the
values of k in progeny of vitiligo affected families
and ks in the sibs of the probands using 0.9% as
population prevalence for the calculation of k.2
Fur-
ther, to estimate the extent of genetic transmission
from affected and unaffected parents to the progeny
in different parental mating types and parental bias
in transmission if any.
Pedigree information on 245 vitiligo families was
obtained from the Central Research Institute for
Unani Medicine (Hyderabad, Andhra Pradesh, India)
of South Indian origin ascertained through proband.
Of the total, 57 cases that were familial and of non-
dermatomal vitiligo type were used for the present
analysis. A significant genetic contribution in the etio-
pathophysiology of vitiligo was reflected from an
overall value of 36.2 of recurrence risk ratio in prog-
eny. Under normal parent · normal parent and
normal parent · affected parent mating types of
probands the values of k and ks were observed to
be 37.66 and 11.49; 34.70 and 12.48 respectively
(P > 0.05) (Table 1).
In order to understand the magnitude of transmis-
sion of the genetic component from parent to off-
spring, ks was calculated for the sibs of the proband.
ks is considered an accurate measure of extent of
genetic involvement when the values are higher than
5, whereas a ratio of less than 2 indicates that famil-
ial aggregation was due to shared environment
rather than shared genes.3,4
The overall relative risk
in affected sibs of the proband was observed to
be 10.79 (19⁄176), which is almost similar to the
value reported by Majumdar et al.5
and ks was esti-
mated to be 11.99. To our knowledge, this is the first
report on the findings of ks among a South Indian
population.
On categorization of probands with respect to
parental mating types, ks was determined to be
11.49 when both the parents were normal (N · N)
and it was increased to 12.48 when one of the
parents was affected (N · A) with vitiligo. Further
sub-categorization by affected mother or father
established an interesting finding for ks values of
9.52 and 14.4, respectively. To confirm the higher ks
value (14.4) when the father was affected, preva-
lence of vitiligo in the 1° and 2° relatives of parents
of the proband with respect to maternal and paternal
relatives were analyzed. It was found that the overall
Table 1. Estimation of k in the progeny of different parental mating types
Affected progeny (%) Recurrence risk ratio (k)
Total Male Female Total Male Female
N · N (31) 118 40 (33.8) 21 (38.1) 19 (30.1) 37.66 37.8 33.5
N · A (26) 115 36 (31.3) 21 (36.2) 15 (26.3) 34.7 40.2 29.2
N · N, normal parent · normal parent; N · A, normal parent · affected parent.
Correspondence: Parveen Jahan, Ph.D., Department of Genetics, Osmania University, Hyderabad, Andhra Pradesh 500012, India. Email:
parveenjahan_dr@yahoo.in
doi: 10.1111/j.1346-8138.2010.01123.x Journal of Dermatology 2011; 38: 1–3
Ó 2011 Japanese Dermatological Association 1

2. prevalence was approximately 8.4% (48⁄567), where
6% (17⁄285) was in maternal relatives and 11% in
paternal relatives. The increased prevalence in the
relatives of the male parent could be correlated to
the higher ks. This increased ks value through the
affected father reflected in the male sibs of the
proband compared to female sibs (P < 0.001;
Table 2) suggests that the sex of the disease-
transmitting parent could influence the expression of
the disease in the offspring which is the parent-
of-origin effect.
In vitiligo, being a polygenic condition, the rate of
transmission of disease from male or female parents
to offspring is more or less comparable. In the pres-
ent study, it was noted that the proportion of pater-
nal transmission of the disease was significantly
higher than expected. Out of 47 transmissions,
20 (42.5%) were showing mother-to-child and
27 (57.5%) showing father-to-child transmission
(P < 0.05). Similar observations have been repor-
ted in a study of parent–child pairs with psoriatic
arthritis. Our observations are pointing towards the
possibility of genomic imprinting, defined as the
differential behavior of genes depending on the par-
ent-of-origin that could play a role in causing the
disease and suggestive of paternal transmission
and maternal imprinting of the gene(s) implicated in
vitiligo.6–8
This type of parent-of-origin effect in
vitiligo has not been reported earlier. It is interesting
to note that autoimmune psoriatic arthritis and viti-
ligo have an autoimmune etiology in common and
also appear to have parent-of-origin effect.
On segregating parental transmissions, it was
noted that the father was transmitting disease genes
two times more to sons than to daughters suggestive
of paternal transmission with maternal imprinting
(ks 19.1 vs 8.8, OR = 2 [1.6–3.2], P < 0.001). Further,
we observed higher ks for male offspring compared
to female offspring when the father was affected. The
immune system of females differs from that of males
because estrogens encourage immunological pro-
cesses driven by CD4+
T-helper cell (Th)2 cells and
B cells, whereas androgens enhance CD4+
Th1
and CD8+
cell activity. The enhanced expression
observed in the present study may be striking due to
the influence of androgens in the male offspring
on disease-causing genes as suggested in some
Th1-mediated diseases Ackerman.9
Such information is required to ascertain the mag-
nitude of the genetic component before initiating
any genome-wide analysis to identify susceptible
loci. Studies involving various ethnic groups and dif-
ferent populations may help to establish the above
finding. To confirm at a molecular level, markers on
various chromosomes that have already been impli-
cated in susceptibility to vitiligo by genome-wide
scanning may be conditioned on paternal trans-
mission in order to provide evidence for genomic
imprinting.
Tipisetty SUREKHA, Mohammed ISHAQ,
Parveen JAHAN
Department of Genetics, Osmania University, Hyderabad,
Andhra Pradesh, India
REFERENCES
1 Surekha T, Ishaq M, Latha KP, Rao PH, Jahan P. Do clini-
cal variants of vitiligo involve X-chromosomal gene(s)
too? J Med Sci, 2008; 8(8): 728–733.
2 Rao PH, Waheed MA, Hussain SJ. Risk figures for vitiligo
among the relatives of the probands. Indian J Hum Genet
1999; 5(1): 41–44.
3 Khoury MJ, Beaty TH, Liang KY. Can familial aggregation
of disease be explained by environmental risk factores?
Am J Epidemiol 1988; 127: 674–683.
Table 2. Estimation of ks with different parental mating types
Affected sibs (%) Sibling recurrence risk ratio (ks)
Total Male Female Total Male Female
N · N 87 9 (10.34) 4 (10.5) 5 (10) 11.49 11.66 11.11
N · A 89 10 (11.23) 6 (13.9) 4 (8.6) 12.48 15.44 9.5
NF · AM 35 3 (8.57) 1 (7.1) 2 (9.5) 9.52 7.8 10.5
NM · AF 54 7 (12.9) 5 (17.2) 2 (8) 14.4 19.1 8.8
N · N, normal parent · normal parent; N · A, normal parent · affected parent; NF · AM, normal father · affected mother; NM · AF, normal
mother · affected father.
2 Ó 2011 Japanese Dermatological Association
T. Surekha et al.

3. 4 Risch N. Linkage strategies for genetically complex traits
II. The power of affecetd relative pairs. Am J Hum Genet
1990; 46: 229–241.
5 Majumdar PP, Nordlund JJ, Nath SK. Pattern of familial agg-
regation of vitiligo. Arch Dermatol 1993; 129(8): 994–998.
6 Andrew Z, Edith SS, Susan DT, David NG, Sampath P.
Familial autoimmunity: maternal parent-of-origin effect in
juvenile idiopathic arthritis. Clin Rheumatol 2008; 27(2):
241–244.
7 Karason A, Johann EG, Ruchi U et al. A susceptibility
gene for psoriatic arthritis maps to chromosome 16q:
evidence for imprinting. Am J Hum Genet 2003; 72:
125–131.
8 Rahman P, Gladman DD, Schentag CT et al. Excessive
paternal transmission in psoriatic arthritis. Arthritis
Rheum 1999; 42: 1228–1231.
9 Ackerman L. Sex hormones and the genesis of auto-
immunity. Arch Dermatol 2006; 142: 371–376.
Ó 2011 Japanese Dermatological Association 3
Letter to the Editor