CORRESPONDENCE 1433
Response
Το the Editor
M y o c a r d i a l m f a r c t i o n is a rare b u t d e v a s t a t m g disease a m o n g y o u n g w o m e n Theie aie iew studies a v a i l a b l e and data on genetic nsk f a c t o i s aie especially scarce Therefore the attempt of A m o w i t z et al to cvaluate our fmdmgs m a new study is c o m m e n d a b l e H o w e v e r the size of then study (36 patients) makes it d i f f i c u l t to Interpret their Undings This becomes clear w h e n we look at the c o n f i d e n c e intervals of then i c s u l t s and o u r r e s u l t s
We s l u d i e d 84 patients and 388 c o n t i o l s and f o u n d (with prevalences ot carnership of hctor V Leiden o( 10% and 4%) a relative nsk ot 2 4 with a 95% conhdence mlerval ot l 0 to 5 9 ' The nsk was 25 to 32 f o l d mcreased in carners with othei m a j o i nsk factois äs compared w i t h n o n c a r n e r s w i t h o u t other m a j o r nsk f a c t o r s A m o w i t z et al r e p o i t l carrier a m o n g 36 p a l i e n t s (2 7%) and 3 a m o n g 36 c o n t r o l s (8 3) w h i c h leads to a relative nsk of 0 3 w i t h a c o n h d e n c e i n t e r v a l of 0 01 to 4 20 l rom t h i s w e c o n c l u d c t h a t t h e s c d a t a neilher s u p p o r t n o r r e f u t e o u r p r c v i o u s largei s t u d y The l a i g e d i s c i e p a n c y in the e s t i m a t e s ot the carrier p r e v a l e n c e a m o n g c o n t i o l s (8 3% a m o n g 36 c o n t i o l s and 4 8% i m o n g 948 c o n t r o l s ) illustrates the i n s t a b i l i t y of estimates bascd on s u c h s m a l l s a m p l e s
R e c e n t l y w e h a v e s h o w n t h a t a n o l h e i c o m m o n p i o t h i o m b o t i c m u t a t i o n the 2 0 2 1 0 G to A v a i i a n t of the p i o t i o m b i n g e n e w h i c h is p i e s e n t m 2% to 4% of w h i t e s - increases the nsk ot m y o c a i d i a l m l a r c t i o n l o u r f o l d m y o u n g w o m e n3 and t h a t the c o m b m a t i o n ot the m u t a t i o n with a m a j o r c a r d i o v a s c u l a r nsk f a c t o r leads to a 43 f o l d increased nsk ( c o m p a i e d w i t h w o m e n with n e i t h e r ) A l u i t h e i a n a l o g y m a y be l o u n d m a large s t u d y a m o n g ( m a i n l y m i d d l e a g e d ) m e n w i t h m y o c a r d i a l m f a r c t i o n (560 p a t i e n t s and 646 con trols) to which we tound m i l d l y e l i v a t e d nsks associated w i t h b o t h t a c t o i V I eiden and p r o t h r o m b m 20210A and also m o r e pro n o u n c e d nsks in the presence ot other nsk f a c l o r s4 We f e e l t h a t the m a g n i t u d e ot these nsks estimates and the a n a l o g i e s b e t w e e n the two
a b n o r m a h t i e s and the sexes indicate the associations to be real N e v e r t h e l e s s we too are m t e r e s t e d in e x t e n d i n g these h n d i n g s tor w h i c h larger p o p u l a l i o n b a s e d s t u d i e s are u n d e r way m Seattle and Leiden
F R R o s e n d a a l
Himoitaw and Thrombo^ii Reuartli Center Leiden Unnemn Medital Center
Leiden The Netherlandi
D S Siscovick
Cardioia<:iular Health Rneanh Unit U n n e r f i n of Washington
Seattle WA REFERENCES
1 R o s t n d a a l FR Siscovick DS S c h w a r t z SM B e v e r l y RK Psaty BM L o n g s t i e t h WT Ji R a g h u n a t h a n TE K o e p s e l l TD R e i t s m a PH Factor V Leiden ( l e s i s t a n c e to a c t i v a t e d p i o t e i n C) increases the risk ot m y o c a r d i a l mhrction in y o u n g w o m e n B l o o d 89 2817
1997 2 R o s e n d a a l FR D o g g e n CJM Zivelin A A i r u d a VR A i a c h M Siscovick DS H i l l a r p A W a t z k e HH B e m a r d i F C u m m i n g AM P i e s t o n FE R e i t s m a PH G e o g i a p h i c d i s t i i b u t i o n of the 2 0 2 1 0 G to A p r o t h r o m b m v a r i a n t T h r o m b H a e m o s t 79 706 1998 3 R o s e n d a a l FR Siscovick DS S c h w a r t z SM Psaty BM R a g h u n a t h a n TE Vos HL A c o m m o n p i o t h i o m b m v a r i a n t (20210 G to A) i n c i e a s e s the nsk of m y o c a r d i a l m f a r c t i o n m y o u n g w o m e n Blood 90 1747 1997 4 D o g g e n CJM M a n g e r C a t s V Bertina RM R o s e n d a a l FR I n t e r a c t i o n of c o a g u l a t i o n detects and c a r d i o v a s c u l a r risk f a c l o r s I n c i e a s e d nsk of m y o c a r d i a ] m f a i c t i o n a s s o c i a t e d w i t h f a c t o r V Leiden 01 p r o t h r o m b m 2 0 2 1 0 A Circulation 97 1037 1998
GATA-1 Transcription Factor Transactivates the Promoter for CCR5, a Coreceptor
for Human Immunodeficiency Virus Type 1 Entry
To the Ldnor I n l e c t i o n o f h o s t cells b y h u m a n i m m u n o d e h c i c n c y v n u s t y p e l (HIV 1) is d e t e i m m e d by b i n d i n g ot the v i r a l e n v e l o p e to the CD4 m o l c c u l c äs w e l l äs to a c o i e c e p t o r such äs C C R 5 or C X C R 4 ' E x p i c s s i o n öl CCR5 is a p p a i e n t l y lestncted to c e i t a i n cell t y p e s (le l y m p h o c y t e s m o n o c y t e / m a c r o p h a g e s or C D 3 4+ progenitor cells) '4 which are susceptible to m a c r o p h a g e ( M ) t i o p i c (01 R5) slrains of HIV l B e c a u s e m o s t p n m a r y isolates of HIV I use C C R 5 to cnter cells and levels of C C R 5 e x p i e s s i o n c o n e l a t e w e l l w i t h the m l e c t a b i l i l y w i t h M t i o p i c HIV l in vilro ' it is i m p o r t a n t to delincite the c e l l u l a r ind m o l e c u l a r m e c h a n i s m s w h e r e b y ex p i e s s i o n o f C C R 5 is r e g u l a l e d T h e p r e s e n t s t u d y d e m o n s t i a t e s t h a t (he transcnption t a c t o r GATA l can u p r e g u l a t c C C R 5 p r o m o t e r activ ity
The C C R 5 p r o m o t e r region c o n t a m s at least three GATA b m d m g c l c m c n t s (Fig 1A) We have p r e v i o u s l y identihed one ot those ele m e n t s äs i GATA l b m d m g Site4 and h a v e d e s i g n a t e d it äs G A T A # 1 C h a i a c t e r i z a t i o n o f t h e t u i t h e i u p s t i e a m i c g i o n d e m o n s t i a t e d •mother GATA b m d m g Site ( G A T A # 2 ) b e t w e e n - 7 3 4 a n d 7 3 9
l e l a t i v e to the t i a n s c i i p t i o n s t a t t site (TSS4 d a t a not s h o w n ) F u i t h e i c h a i a c t e n z a t i o n o f t h e p i o m o t e r s h o w e d t h a t o n e o f t h e D N a s e protected areas (FP 5)4 c o n t a m s a n o n c o n s e n s u s GATA e l e m e n t (Fig
