Histidine　decarboxylase　gene　(HDC)　encodes　histidine　decarboxylase　which　is　the　crucial　enzyme　for　the　biosynthesis　of　histidine.　Studies　have　shown　that　histamine　is　likely　to　be　involved　in　the　regulation　of　reproduction　system.　To　find　the　possible　correlation　between　HDC　gene　and　AANM　(age　at　natural　menopause),　we　selected　265　postmenopausal　women　from　131　nuclear　families　and　performed　a　transmission　disequilibrium　test.　Significant　within-family　associations　with　AANM　for　SNP　rs854163　and　SNP　rs854158　of　HDC　gene　were　observed　(P　values　=　0.0018　and　0.0197,　respectively).　After　1000　permutations,　SNP　rs854163　still　remained　significant　within-family　association　with　AANM.　Consistently,　we　also　detected　a　significant　within-family　association　between　haplotype　block　2　(defined　by　SNP　rs854163　and　rs860526)　and　AANM　in　the　haplotype　analyses　(P　value　=　0.0397).　Our　results　suggest　that　the　HDC　gene　polymorphisms　are　significantly　associated　with　AANM　in　Caucasian　women.　(c)　2006　Elsevier　Inc.　All　rights　reserved.