Variation in the PON1 and PON2 genes has been shown to be associated with c
oronary heart disease risk in adults of South Asian origin. In this group,
low birth weight is also associated with coronary heart disease risk, We th
erefore hypothesized that variation in PON1 and PON2 genes may be associate
d with Variation in birth weight. This relationship was examined in 290 con
secutive Trinidadian neonates of different ethnic origins. We found that Va
riation in PON2 was significantly associated with variation in birth weight
in Trinidadian neonates of South Asian origin. Among the neonates of South
Asian origin, those who were homozygous for PON2 A148/A148 had significant
ly lower birth weight, by approximately 200 g, compared with those with the
other two genotypes (P < 0.05). For neonates of South Asian origin, PON2 A
148/A148 homozygotes were significantly more prevalent in those comprising
the lowest tertile for birth weight than those comprising the highest terti
le (0.41 versus 0.24, P < 0.05). There were no significant associations of
PON2 variation with any phenotype in other ethnic groups. We conclude that
among neonates of South Asian origin, homozygosity for PON2 A148/A148, is a
ssociated with significantly lower birth weight. This suggests that genetic
factors in the fetus may be important determinants of neonatal birth weigh
t and possibly of more distal adult phenotypes, such as coronary heart dise
ase. Pharmacogenetics 9:351-356 (C) 1999 Lippincott Williams & Wilkins.