Page 1 * @ > @ @ > > > @ . 1 < @ > > @ > > @ < < > < 2 ...

1 downloads 0 Views 229KB Size Report
Jun 17, 1991 - women, and migraine: the role of sex, hormones, .... gene variant (MTHFR C677T) and migraine: a case control study and meta-analysis.
‫ﻣﺠﻠﻪ داﻧﺸﻜﺪه ﭘﺰﺷﻜﻲ اﺻﻔﻬﺎن‬

‫ﻣﻘﺎﻟﻪ ﭘﮋوﻫﺸﻲ‬

‫ﺳﺎل ﺳﻲام‪/‬ﺷﻤﺎره ‪/214‬ﻫﻔﺘﻪ ﭼﻬﺎرم دي ﻣﺎه ‪1391‬‬

‫ﺗﺎرﻳﺦ درﻳﺎﻓﺖ‪91/6/17 :‬‬

‫ﺗﺎرﻳﺦ ﭘﺬﻳﺮش‪91/8/20 :‬‬

‫ﺑﺮرﺳﻲ ﭘﻠﻲﻣﻮرﻓﻴﺴﻢ ژﻧﺘﻴﻜﻲ ‪ C677T‬در ژن ‪ MTHFR‬در ﺑﻴﻤﺎران ﻣﺒﺘﻼ ﺑﻪ ﻣﻴﮕﺮن در‬ ‫ﻣﻘﺎﻳﺴﻪ ﺑﺎ ﮔﺮوه ﺷﺎﻫﺪ‬ ‫ﻛﺎﻣﻴﺎر ﻫﻤﺖ‪ ،1‬دﻛﺘﺮ ﺷﻘﺎﻳﻖ ﺣﻖﺟﻮي ﺟﻮاﻧﻤﺮد‪ ،2‬دﻛﺘﺮ ﻣﺤﻤﺪ ﺳﻌﺎدتﻧﻴﺎ‪ ،3‬ﻻﻟﻪ رﻓﻴﻌﻲ‪،4‬‬ ‫‪5‬‬

‫ﻋﻠﻴﺮﺿﺎ زﻧﺪيﻓﺮ‪ ،1‬ﻣﺤﻤﺪﺣﺴﻦ ﺗﺎجاﻟﺪﻳﻨﻲ‬ ‫ﭼﻜﻴﺪه‬

‫ﻣﻘﺪﻣﻪ‪ :‬ﻣﻴﮕﺮن ﺑﻪ ﻋﻨﻮان ﻓﻨﻮﺗﻴﭙﻲ از اﺧﺘﻼﻻت ﭘﻠﻲژﻧﻲ در ﻧﻈﺮ ﮔﺮﻓﺘﻪ ﻣﻲﺷﻮد و ﻣﻨﻌﻜﺲﻛﻨﻨﺪهي اﺛﺮ ﭼﻨﺪﻳﻦ ﺟﺎﻳﮕﺎه ژﻧﻲ ﻣﻲﺑﺎﺷﺪ ﻛﻪ ﻓﺮاﻳﻨﺪﻫﺎي‬ ‫ﭘﺎﺗﻮﻓﻴﺰﻳﻮﻟﻮژﻳﻜﻲ ﻣﺘﻔﺎوﺗﻲ را ﺗﻌﺪﻳﻞ ﻣﻲﻛﻨﻨﺪ‪ .‬ﻧﺸﺎن داده ﺷﺪه اﺳﺖ ﻛﻪ اﻟﻞ ‪ 677T‬در ژن ‪(Methylenetetrahydrofolate reductase) MTHFR‬‬ ‫ﺑﻪ ﻃﻮر ﻣﺴﺘﻘﻴﻢ ﺑﺎ ﻛﺎﻫﺶ ﻓﻌﺎﻟﻴﺖ آﻧﺰﻳﻢ و ژﻧﻮﺗﻴﭗ ﻫﻤﻮزﻳﮕﻮت ‪ TT‬ﺑﻪ ﻃﻮر ﻏﻴﺮ ﻣﺴﺘﻘﻴﻢ ﺑﺎ ﻫﻴﭙﺮﻫﻤﻮﺳﻴﺴﺘﺌﻴﻨﻤﻲ در ارﺗﺒﺎط اﺳﺖ‪ .‬در اﻳﻦ ﻣﻄﺎﻟﻌﻪ ارﺗﺒﺎط‬ ‫ﭘﻠﻲﻣﻮرﻓﻴﺴﻢ ژﻧﺘﻴﻜﻲ ‪ C677T‬در ژن ‪ MTFHR‬و ﻣﻴﮕﺮن در دو ﮔﺮوه ﻣﺒﺘﻼﻳﺎن ﺑﻪ ﻣﻴﮕﺮن و اﻓﺮاد ﺳﺎﻟﻢ در ﺟﻤﻌﻴﺖ اﻳﺮاﻧﻲ ﺑﺮرﺳﻲ ﮔﺮدﻳﺪ‪.‬‬ ‫روشﻫﺎ‪ 203 :‬ﻧﻔﺮ از اﻓﺮاد ﻣﺒﺘﻼ ﺑﻪ ﻣﻴﮕﺮن و ﺳﺎﻟﻢ در اﻳﻦ ﻣﻄﺎﻟﻌﻪ وارد ﺷﺪﻧﺪ‪ .‬ﭘﻠﻲﻣﻮرﻓﻴﺴﻢ ژﻧﺘﻴﻜﻲ ‪ C677T‬در ژن ‪ MTFHR‬در ‪ 102‬ﻧﻔﺮ از ﻣﺒﺘﻼﻳﺎن‬ ‫ﺑﻪ ﻣﻴﮕﺮن و ‪ 101‬ﻓﺮد ﺳﺎﻟﻢ ﺑﺎ اﺳﺘﻔﺎده از ﺗﻜﻨﻴﻚ ‪ (Polymerase chain reaction-High resolution melting-) PCR-HRM‬ﺑﺮرﺳﻲ ﺷﺪ‪.‬‬ ‫ﻳﺎﻓﺘﻪﻫﺎ‪ :‬ﻓﺮاواﻧﻲ ژﻧﻮﺗﻴﭗﻫﺎ در دو ﮔﺮوه ﻣﻮرد و ﺷﺎﻫﺪ در اﻳﻦ ﻣﻄﺎﻟﻌﻪ اﺧﺘﻼف ﻣﻌﻨﻲداري ﻧﺪاﺷﺖ‪ .‬اﺧﺘﻼف ﻓﺮاواﻧﻲ ژﻧﻮﺗﻴﭗ ‪ TT‬ﻧﻴﺰ در دو ﮔﺮوه ﻣﻌﻨﻲدار‬

‫ﻧﺒﻮد )‪.(OR = 0/667 ،CI95%: 0/188-2/362 ،P = 0/530‬‬ ‫ﻧﺘﻴﺠﻪﮔﻴﺮي‪ :‬اﻳﻦ ﻣﻄﺎﻟﻌﻪ ﻧﺸﺎن داد ﭘﻠﻲﻣﻮرﻓﻴﺴﻢ ژﻧﺘﻴﻜﻲ ‪ C677T‬در ژن ‪ MTFHR‬در اﺳﺘﻌﺪاد اﺑﺘﻼ ﺑﻪ ﻣﻴﮕﺮن ﻧﻘﺸﻲ ﻧﺪاﺷﺖ‪ .‬اﻳﻦ اوﻟﻴﻦ ﻣﻄﺎﻟﻌﻪاي ﺑﻮد‬ ‫ﻛﻪ ﺑﻪ ﺑﺮرﺳﻲ ﻓﺮاواﻧﻲ اﻳﻦ ﭘﻠﻲﻣﻮرﻓﻴﺴﻢ در ﺟﻤﻌﻴﺖ اﻳﺮاﻧﻲ ﭘﺮداﺧﺖ‪ .‬ﭘﻴﺸﻨﻬﺎد ﻣﻲﺷﻮد اﻳﻦ ﻣﻄﺎﻟﻌﻪ ﺑﺎ ﺗﻌﺪاد ﻧﻤﻮﻧﻪ ﺑﻴﺸﺘﺮ اﻧﺠﺎم ﺷﻮد‪ ،‬ﻫﻤﭽﻨﻴﻦ ﻣﻮارد ﺑﺎ و ﺑﺪون‬ ‫اورا )‪ (Eura‬ﺑﻪ ﻃﻮر ﺟﺪاﮔﺎﻧﻪ ﺑﺮرﺳﻲ ﺷﻮد‪.‬‬ ‫واژﮔﺎن ﻛﻠﻴﺪي‪ :‬ﭘﻠﻲﻣﻮرﻓﻴﺴﻢ ژﻧﺘﻴﻜﻲ‪ ،‬ﻣﻴﮕﺮن‪ ،‬ژن ‪(Methylenetetrahydrofolate reductase) MTFHR‬‬

‫ﻣﻘﺪﻣﻪ‬

‫اﻳﺠﺎدﻛﻨﻨﺪه ي ﻧﺎﺗﻮاﻧﻲ ﺑﻪ ﺧﻮد اﺧﺘﺼﺎص داده اﺳﺖ و در‬

‫ﻣﻴﮕﺮن ﻳﻜﻲ از ﺷـﺎﻳﻊﺗـﺮﻳﻦ اﻧـﻮاع ﺳـﺮ درد در ﻫﻤـﻪ ي‬

‫ﺑﻴﻦ زﻧﺎن در ﻣﺮﺗﺒﻪي ‪ 12‬ﻗﺮار دارد‪ .‬ﺷﻴﻮع ﺣﻤـﻼت ﺳـﺮ‬

‫ﺟﻮاﻣــﻊ ﺑﺸــﺮي از ﺟﻤﻠــﻪ اﻳــﺮان ﺑــﻪ ﺷــﻤﺎر ﻣــﻲرود و‬

‫درد در زﻧـﺎن ﺗــﺎ ‪ 17‬درﺻــﺪ و در ﻣـﺮدان ﺗــﺎ ‪ 6‬درﺻــﺪ‬

‫ﻣﻲ ﺗﻮاﻧﺪ اﺑﻌﺎد زﻧﺪﮔﻲ ﻓﺮد ﻣﺒﺘﻼ را ﺗﺤﺖ ﺗﺄﺛﻴﺮ ﻗﺮار دﻫﺪ‪.‬‬

‫ﮔﺰارش ﺷﺪه اﺳﺖ‪ .‬ﻣﻴﮕﺮن ﺷﺎﻣﻞ ﺳﺮ دردﻫﺎي ﻣﻜﺮر ﺑـﻪ‬

‫ﺑﺮ اﺳﺎس ﮔـﺰارش ﺳـﺎزﻣﺎن ﺟﻬـﺎﻧﻲ ﺑﻬﺪاﺷـﺖ‪ ،‬ﻣﻴﮕـﺮن‬

‫ﻫﻤــﺮاه ﻋﻼﻳـﻢ ﮔﻮارﺷــﻲ ﻣﺎﻧﻨــﺪ ﺗﻬــﻮع‪ ،‬اﺳــﺘﻔﺮاغ و ﻧﻴــﺰ‬

‫رﺗﺒـــﻪي ﻧـــﻮزدﻫﻢ را در ﺑـــﻴﻦ ﻫﻤـــﻪي اﺧـــﺘﻼﻻت‬

‫ﻓﺘﻮﻓﻮﺑﻴﺎ و ﻓﻨﻮﻓﻮﺑﻲ ﻣﻲﺑﺎﺷﺪ‪ .‬اﻳﻦ ﺳﺮ درد اﻏﻠﺐ ﻣﺎﻫﻴـﺖ‬

‫* اﻳﻦ ﻣﻘﺎﻟﻪ ﺣﺎﺻﻞ ﭘﺎﻳﺎنﻧﺎﻣﻪي دورهي دﻛﺘﺮاي ﺣﺮﻓﻪاي در داﻧﺸﮕﺎه ﻋﻠﻮم ﭘﺰﺷﻜﻲ اﺻﻔﻬﺎن اﺳﺖ‪.‬‬ ‫‪ 1‬داﻧﺸﺠﻮي ﭘﺰﺷﻜﻲ‪ ،‬داﻧﺸﻜﺪهي ﭘﺰﺷﻜﻲ و ﻛﻤﻴﺘﻪي ﺗﺤﻘﻴﻘﺎت داﻧﺸﺠﻮﻳﻲ‪ ،‬داﻧﺸﮕﺎه ﻋﻠﻮم ﭘﺰﺷﻜﻲ اﺻﻔﻬﺎن‪ ،‬اﺻﻔﻬﺎن‪ ،‬اﻳﺮان‬ ‫‪ 2‬داﻧﺸﻴﺎر‪ ،‬ﻣﺮﻛﺰ ﺗﺤﻘﻴﻘﺎت ﻓﻴﺰﻳﻮﻟﻮژي ﻛﺎرﺑﺮدي‪ ،‬داﻧﺸﮕﺎه ﻋﻠﻮم ﭘﺰﺷﻜﻲ اﺻﻔﻬﺎن‪ ،‬اﺻﻔﻬﺎن‪ ،‬اﻳﺮان‬ ‫‪ 3‬داﻧﺸﻴﺎر‪ ،‬ﻣﺮﻛﺰ ﺗﺤﻘﻴﻘﺎت ﻋﻠﻮم اﻋﺼﺎب و ﮔﺮوه اﻋﺼﺎب‪ ،‬داﻧﺸﻜﺪهي ﭘﺰﺷﻜﻲ‪ ،‬داﻧﺸﮕﺎه ﻋﻠﻮم ﭘﺰﺷﻜﻲ اﺻﻔﻬﺎن‪ ،‬اﺻﻔﻬﺎن‪ ،‬اﻳﺮان‬ ‫‪ 4‬ﻣﺮﻛﺰ ﺗﺤﻘﻴﻘﺎت ﻓﻴﺰﻳﻮﻟﻮژي ﻛﺎرﺑﺮدي‪ ،‬داﻧﺸﮕﺎه ﻋﻠﻮم ﭘﺰﺷﻜﻲ اﺻﻔﻬﺎن‪ ،‬اﺻﻔﻬﺎن‪ ،‬اﻳﺮان‬ ‫‪ 5‬داﻧﺸﺠﻮي ﻛﺎرﺷﻨﺎﺳﻲ ارﺷﺪ‪ ،‬ﻣﺮﻛﺰ ﺗﺤﻘﻴﻘﺎت ﻓﻴﺰﻳﻮﻟﻮژي ﻛﺎرﺑﺮدي و ﮔﺮوه ﺑﻴﻮﺷﻴﻤﻲ ﺑﺎﻟﻴﻨﻲ‪ ،‬داﻧﺸﻜﺪي داروﺳﺎزي و ﻣﺮﻛﺰ ﺗﺤﻘﻴﻘﺎت ﻋﻠﻮم داروﻳﻲ‪ ،‬داﻧﺸﮕﺎه ﻋﻠﻮم ﭘﺰﺷﻜﻲ اﺻﻔﻬﺎن‪،‬‬ ‫اﺻﻔﻬﺎن‪ ،‬اﻳﺮان‬ ‫‪Email: [email protected]‬‬

‫ﻧﻮﻳﺴﻨﺪهي ﻣﺴﺆول‪ :‬ﻣﺤﻤﺪﺣﺴﻦ ﺗﺎجاﻟﺪﻳﻨﻲ‬

‫ﻣﺠﻠﻪ داﻧﺸﻜﺪه ﭘﺰﺷﻜﻲ اﺻﻔﻬﺎن – ﺳﺎل ‪ / 30‬ﺷﻤﺎره ‪ /214‬ﻫﻔﺘﻪ ﭼﻬﺎرم دي ‪1391‬‬ ‫‪www.mui.ac.ir‬‬

‫‪1935‬‬

‫ﭘﻠﻲﻣﻮرﻓﻴﺴﻢ ژﻧﺘﻴﻜﻲ ‪ C677T‬در ژن ‪ MTHFR‬در ﺑﻴﻤﺎران ﻣﺒﺘﻼ ﺑﻪ ﻣﻴﮕﺮن‬

‫ﻛﺎﻣﻴﺎر ﻫﻤﺖ و ﻫﻤﻜﺎران‬

‫ﺿﺮﺑﺎندار و ﻳﻚ ﻃﺮﻓﻪ دارد و ﺑﺎ ﻓﻌﺎﻟﻴﺖﻫﺎي ﻓﻴﺰﻳﻜـﻲ و‬

‫ﻫﻤﻮﺳﻴﺴــﺘﺌﻴﻦ ﺑــﻪ ﻣﺘﻴــﻮﻧﻴﻦ اﺳــﺖ )‪ .(8-11‬ﻣﻮﺗﺎﺳــﻴﻮن‬

‫ﺣﺮﻛﺘﻲ ﺗﺸﺪﻳﺪ ﻣـﻲ ﺷـﻮد‪ .‬در ﻃﺒﻘـﻪﺑﻨـﺪي ﺟﺪﻳـﺪ ‪IHS‬‬

‫‪ C677T‬در ﻣﺘــﻴﻠﻦ ﺗﺘﺮاﻫﻴــﺪروﻓﻮﻻت ردوﻛﺘــﺎز ﺑﺎﻋــﺚ‬

‫)‪ ،(International headache society‬ﻣﻴﮕــﺮن ﺑــﻪ دو‬

‫ﺟﺎﻳﮕﺰﻳﻨﻲ واﻟﻴﻦ ﺑﺎ آﻻﻧﻴﻦ ﻣﻲ ﺷﻮد‪ .‬ژﻧﻮﺗﻴﭗ ﻫﻤﻮزﻳﮕﻮت‬

‫دﺳﺘﻪي ﻣﻴﮕﺮن ﻫﻤـﺮاه ﺑـﺎ ‪ Eura‬و ﻣﻴﮕـﺮن ﺑـﺪون ‪Eura‬‬

‫‪ TT‬ﻫﻤــﺮاه ﺑــﺎ اﻓــﺰاﻳﺶ ﺳــﻄﺢ ﺧــﻮﻧﻲ ﻫﻮﻣﻮﺳﻴﺴــﺘﺌﻴﻦ‬

‫ﺗﻘﺴﻴﻢ ﺷﺪه اﺳﺖ‪ .‬ﻧﺰدﻳﻚ ﺑـﻪ ‪ 20‬درﺻـﺪ ﻣﺒﺘﻼﻳـﺎن ﺑـﻪ‬

‫ﻣﻲ ﺑﺎﺷﺪ ﻛﻪ ﺳـﺒﺐ اﻓـﺰاﻳﺶ ﺧﻄـﺮ ﺗﺮوﻣﺒـﻮز ورﻳـﺪي و‬

‫ﻣﻴﮕﺮن‪ Eura ،‬را ﺗﺠﺮﺑﻪ ﻛﺮدهاﻧﺪ )‪.(1-2‬‬

‫آﺗﺮواﺳــﻜﻠﺮوز ﻣــﻲﺷــﻮد‪ .‬ﻣﻘــﺎدﻳﺮ اﻓــﺰاﻳﺶﻳﺎﻓﺘــﻪي‬

‫در ﻣﻄﺎﻟﻌﺎت ﻣﺨﺘﻠﻔﻲ ﺑﺮ اﻳﻦ ﻧﻜﺘﻪ ﺗﺄﻛﻴﺪ ﺷﺪه اﺳﺖ‬

‫ﻫﻮﻣﻮﺳﻴﺴﺘﺌﻴﻦ ﻣﻲﺗﻮاﻧﺪ ﺑـﻪ ﻋﻨـﻮان ﻳـﻚ اﺳـﻴﺪ آﻣﻴﻨـﻪ ي‬

‫ﻛﻪ ﺑﻴﻤﺎران ﻣﺒﺘﻼ ﺑﻪ ﻣﻴﮕﺮن از ﻧﻮﻋﻲ اﺧـﺘﻼل ﻋﻤﻠﻜـﺮد‬

‫ﻣﺤﺮك ﻋﻤﻞ ﻧﻤﺎﻳﺪ و آﺳﺘﺎﻧﻪي ﺳﺮ درد ﻣﻴﮕﺮﻧﻲ را ﻣﺘـﺄﺛﺮ‬

‫ﻋﺮوﻗﻲ رﻧﺞ ﻣﻲﺑﺮﻧـﺪ )‪ .(3‬اﻟﺘﻬـﺎب ﻣﻮﺿـﻌﻲ ﻧﺎﺷـﻲ از‬

‫ﺳﺎزد )‪ .(11‬ﻧﺘﻴﺠـﻪي ﺑـﺎﻟﻴﻨﻲ اﻓـﺰاﻳﺶ ﻫﻮﻣـﻮ ﺳﻴﺴـﺘﺌﻴﻦ‬

‫آزادﺳــﺎزي ﻣــﺪﻳﺎﺗﻮرﻫﺎ از ﺳــﻠﻮلﻫــﺎي اﻟﺘﻬــﺎﺑﻲ در‬

‫ﭘﻼﺳﻤﺎ ﺷـﺎﻣﻞ آﺳـﻴﺐ ﺳـﻠﻮل ﻫـﺎي اﻧـﺪوﺗﻠﻴﺎل و ﺗﻐﻴﻴـﺮ‬

‫ﭘﺎﺳﺦ ﻫﺎي ﻧﻮروﻧﻲ و در ﻧﺘﻴﺠﻪ‪ ،‬وﻗﻮع ﺳـﺮ درد ﻣﻴﮕـﺮن‬

‫وﻳﮋﮔﻲ ﻫﺎي اﻧﻌﻘﺎدي ﺧﻮن و ﻛﺎﻫﺶ داﻳﻤﻲ ﺳـﻠﻮل ﻫـﺎي‬

‫ﻧﻘﺶ اﺳﺎﺳﻲ دارد‪ .‬ﻣﺎﺳﺖ ﺳﻞ ﻫﺎي ﻣﻨﻨﮋﻳﺎل در ﻋـﺮوق‬

‫‪ Trigeminal‬ﻣﻲ ﺷﻮد )‪ .(12‬ﻛﺎﻫﺶ داﻳﻤﻲ ﺳـﻠﻮل ﻫـﺎي‬

‫ﻣﻨﻨﮋﻳﺎل و آﻛﺴﻮن ﻫﺎي ﮔﻴﺮﻧﺪه ي درد ﭼﻨـﻴﻦ ﻧﻘﺸـﻲ را‬

‫‪ Trigeminal‬ﻣﻨﺠﺮ ﺑـﻪ اﻟﺘﻬـﺎب ﻣﻨﻨـﮋ و ﮔﺸـﺎدي ورﻳـﺪ‬

‫ﺑﺎزي ﻣﻲ ﻛﻨﻨـﺪ )‪ .(4‬ﺗﻐﻴﻴـﺮات ﻋﺮوﻗـﻲ در وﻗـﻮع ‪CSD‬‬

‫ﻣﻐﺬي و در ﻧﻬﺎﻳﺖ درد ﻫﻤﺮاه ﺑﺎ ﻣﻴﮕﺮن ﻣﻲ ﺷﻮد‪ .‬از اﻳﻦ‬

‫)‪ (Cortical spreading depression‬ﻣـﺆﺛﺮ ﻫﺴـﺘﻨﺪ ﻛـﻪ‬

‫رو ﻋﺪم ﻋﻤﻠﻜـﺮد ﺻـﺤﻴﺢ ﻫﻮﻣﻮﺳﻴﺴـﺘﺌﻴﻦ ﺑـﻪ وﺿـﻮح‬

‫ﺧﻮد ﻣﻨﺠﺮ ﺑـﻪ وﻗـﻮع ﻣﻴﮕـﺮن ﻣـﻲ ﺷـﻮﻧﺪ )‪ .(5‬در ﻳـﻚ‬

‫ﺑﺎﻋﺖ ﭘﻴﺸﺮﻓﺖ ﻣﻴﮕﺮن در ﺑﻴﻤﺎر ﻣﻲﮔـﺮدد )‪ .(13‬آﺳـﻴﺐ‬

‫ﻣﻄﺎﻟﻌﻪ ﻧﺸﺎن داده ﺷﺪه اﺳﺖ ﻛﻪ در اﻓﺮاد ﻣﺒﺘﻼ ﺑﻪ ﻣﻴﮕﺮن‬

‫اﻛﺴــﻴﺪاﺗﻴﻮ ﺑــﻪ اﻧــﺪوﺗﻠﻴﻮم ورﻳــﺪي از ﻃﺮﻳــﻖ اﻳﺠــﺎد‬

‫اﺧﺘﻼل ﻋﻤﻠﻜﺮد ﻋﻀﻠﻪ ي ﺻـﺎف ﺑـﻪ ﻋﻠـﺖ اﺧـﺘﻼل در‬

‫آﻧﻴﻮن ﻫﺎي ﺳﻮﭘﺮاﻛﺴﻴﺪي ﺑﺎﻋﺚ اﻓﺰاﻳﺶ ﺷـﺎﻧﺲ اﺑـﺘﻼ ﺑـﻪ‬

‫‪ (Guanosine mono phosphate) GMP‬و ﭘﺎﺳﺦﻫـﺎي‬

‫ﺑﻴﻤﺎري ﻣﻴﮕﺮن و دﻳﮕﺮ ﺑﻴﻤﺎريﻫﺎي اﺧﺘﻼل ﻋﺮوﻗﻲ ﻣﺎﻧﻨـﺪ‬

‫ﻫﻤﻮدﻳﻨﺎﻣﻴﻚ ﺑﻪ ‪ ،(Nitric oxide) NO‬وﺟﻮد دارد )‪.(6‬‬

‫‪ Stroke‬ﻣﻲﺷﻮد )‪ .(14‬ﺗﺤﻘﻴﻘﺎت ﻧﺸﺎن ﻣـﻲدﻫـﺪ ‪C677T‬‬

‫در ﺧﺎﻧﻢﻫﺎي ﻣﺒﺘﻼ ﺑﻪ ﻣﻴﮕﺮن ﺑﺎ ‪ Eura‬در ﺳـﻨﻴﻦ ﻗﺒـﻞ از‬

‫از ﻃﺮﻳــﻖ ﺗﻐﻴﻴــﺮ در ﻓﻌﺎﻟﻴــﺖ آﻧﺰﻳﻤــﻲ‪ ،‬ﺑﺎﻋــﺚ اﻓــﺰاﻳﺶ‬

‫ﻣﻨﻮﭘﻮز‪ ،‬ﺷﻮاﻫﺪي از اﻓﺰاﻳﺶ ﻓﻌﺎﻟﻴﺖ اﻧﺪوﺗﻠﻴﺎل و اﺧﺘﻼل‬

‫ﺳﻮﺑﺴﺘﺮا )ﻫﻮﻣﻮﺳﻴﺴـﺘﺌﻴﻦ( ﻣـﻲ ﮔـﺮدد و ﺧﻄـﺮ ﮔﺴـﺘﺮش‬

‫ﻋﻤﻠﻜﺮد ﻋﺮوﻗﻲ وﺟﻮد دارد )‪.(7‬‬

‫ﻣﻴﮕﺮن و دﻳﮕﺮ ﺑﻴﻤﺎريﻫﺎي ﻋﺮوﻗﻲ را اﻓﺰاﻳﺶ ﻣﻲدﻫﺪ‪.‬‬

‫ژن ﻣﺘﻴﻠﻦ ﺗﺘﺮاﻓﻮﻻت ردوﻛﺘﺎز ﻳﺎ ‪MTHFR: EC:1.5.1.2‬‬

‫ﻣﺎ در اﻳﻦ ﻣﻄﺎﻟﻌﻪ ﺑﻪ ﺑﺮرﺳـﻲ ارﺗﺒـﺎط ﭘﻠـﻲﻣﻮرﻓﻴﺴـﻢ‬

‫‪ ،(Methylenetetrahydrofolate‬در‬

‫ژﻧﺘﻴﻜـــﻲ ‪ C677T‬در ژن ‪ MTFHR‬و ﻣﻴﮕـــﺮن در دو‬

‫ﻧﺎﺣﻴﻪ ي ژﻧـﻲ ‪ 1p36.3‬ﻗـﺮار ﮔﺮﻓﺘـﻪ اﺳـﺖ و ﻣﺤﺼـﻮل‬

‫ﮔﺮوه اﻓﺮاد ﻣﺒﺘﻼ ﺑﻪ ﻣﻴﮕـﺮن و اﻓـﺮاد ﺳـﺎﻟﻢ در ﺟﻤﻌﻴـﺖ‬

‫ﭘﺮوﺗﺌﻴﻨــﻲ آن آﻧــﺰﻳﻢ دﺧﻴــﻞ در ﻣﺘﺎﺑﻮﻟﻴﺴــﻢ ﻓــﻮﻻت و‬

‫اﻳﺮاﻧﻲ ﭘﺮداﺧﺘﻴﻢ‪.‬‬

‫)‪reductase‬‬

‫ﻣﺴﺆول ﺗﻮﻟﻴـﺪ ‪ -5‬ﻣﺘـﻴﻠﻦ ﺗﺘﺮاﻫﻴـﺪروﻓﻮﻻت از ‪ 5‬و ‪10‬‬ ‫ﻣﺘﻴﻠﻦ ﺗﺘﺮاﻫﻴﺪروﻓﻮﻻت ﻣﻲ ﺑﺎﺷـﺪ ﻛـﻪ ﻓـﺮم ﻏﺎﻟـﺐ و در‬

‫روشﻫﺎ‬

‫ﮔــﺮدش ﻓــﻮﻻت و دﻫﻨــﺪهي ﻛــﺮﺑﻦ در رﻳﻤﺘﻴﻼﺳــﻴﻮن‬

‫اﻳﻦ ﺗﺤﻘﻴﻖ ﻳﻚ ﻣﻄﺎﻟﻌﻪ ي ﻣـﻮرد‪ -‬ﺷـﺎﻫﺪي ﺑـﻮد ﻛـﻪ ﺑـﺎ‬

‫‪1936‬‬

‫ﻣﺠﻠﻪ داﻧﺸﻜﺪه ﭘﺰﺷﻜﻲ اﺻﻔﻬﺎن – ﺳﺎل ‪ / 30‬ﺷﻤﺎره ‪ /214‬ﻫﻔﺘﻪ ﭼﻬﺎرم دي ‪1391‬‬ ‫‪www.mui.ac.ir‬‬

‫ﭘﻠﻲﻣﻮرﻓﻴﺴﻢ ژﻧﺘﻴﻜﻲ ‪ C677T‬در ژن ‪ MTHFR‬در ﺑﻴﻤﺎران ﻣﺒﺘﻼ ﺑﻪ ﻣﻴﮕﺮن‬

‫ﻛﺎﻣﻴﺎر ﻫﻤﺖ و ﻫﻤﻜﺎران‬

‫ﻫﺪف ﺗﻌﻴﻴﻦ ارﺗﺒﺎط ﭘﻠﻲ ﻣﻮرﻓﻴﺴﻢ ژﻧﺘﻴﻜـﻲ ‪ C677T‬در‬

‫ﭘﻠﻲﻣﻮرﻓﻴﺴﻢ ‪ C677T‬ﻣﻲﺑﺎﺷـﺪ‪ ،‬ﺑـﺎ اﺳـﺘﻔﺎده از ﺗﻜﻨﻴـﻚ‬

‫ژن ‪ MTHFR‬در ﺑﻴﻤﺎران ﻣﺒﺘﻼ ﺑﻪ ﻣﻴﮕﺮن اﻧﺠـﺎم ﺷـﺪ‪.‬‬

‫‪ PCR‬ﺗﻜﺜﻴﺮ ﻛﺮدﻳﻢ‪ .‬ﺑﺮاي اﻳﻦ ﻛﺎر از ﭘﺮاﻳﻤﺮﻫـﺎي رﻓـﺖ‬

‫ﻧﻤﻮﻧﻪ ﻫﺎ از ﺑﻴﻦ ﺑﻴﻤﺎراﻧﻲ ﻛـﻪ ﺑـﺎ ﻋﻼﻳـﻢ ﺳـﺮ درد ﻳـﻚ‬

‫'‪ 5’-TGAAGGAGAAGGTGTCTGCGGGA-3‬و‬

‫ﻃﺮﻓﻪ و ﺿﺮﺑﺎن دار ﻫﻤﺮاه ﺑﺎ ﺗﻬـﻮع‪ ،‬اﺳـﺘﻔﺮاغ‪ ،‬ﺗـﺮس از‬

‫ﺑﺮﮔﺸﺖ '‪5’-AGGACGGTGCGGTGAGAGTG-3‬‬

‫ﻧﻮر و اﺣﺴﺎس ﺧﺴﺘﮕﻲ ﺑﻪ درﻣﺎﻧﮕﺎه اﻋﺼﺎب ﺑﻴﻤﺎرﺳﺘﺎن‬

‫اﺳﺘﻔﺎده ﺷﺪ‪.‬‬

‫اﻟﺰﻫﺮا )س( ﻣﺮاﺟﻌﻪ ﻛﺮده ﺑﻮدﻧﺪ و ﺗﻮﺳـﻂ ﻣﺘﺨﺼﺼـﻴﻦ‬

‫ﻣﺨﻠﻮط اﺳﺘﻔﺎده ﺷﺪه ﺑﺮاي ‪ PCR‬ﺷـﺎﻣﻞ ‪ 20‬ﻧـﺎﻧﻮﮔﺮم‬

‫داﺧﻠـــﻲ اﻋﺼـــﺎب ﺑـــﺮ اﺳـــﺎس ﻛﺮاﻳﺘﺮﻳـــﺎ ‪ICHD-2‬‬

‫از ‪ DNA‬ﻧﻤﻮﻧﻪ‪ 0/5 ،‬ﻣﻴﻠﻲﻟﻴﺘﺮ از ﭘﺮاﻳﻤﺮﻫﺎ ﺑـﺎ ﻏﻠﻈـﺖ ‪10‬‬

‫)‪ (International headache classification‬ﺑﺮاي آنﻫﺎ‬

‫ﻣﻴﻜﺮوﻣﻮل‪ 10 ،‬ﻣﻴﻜﺮوﻟﻴﺘﺮ ‪Type-it HRM Master Mix‬‬

‫ﻣﻴﮕﺮن ﻛﻼﺳـﻴﻚ )ﺑـﺎ ‪ (Eura‬ﻳـﺎ ﻣﻴﮕـﺮن ﺷـﺎﻳﻊ )ﺑـﺪون‬

‫و ‪ 10‬ﻣﻴﻜﺮوﻟﻴﺘﺮ آب ﺑﻮد‪ .‬واﻛﻨﺶ ‪ PCR‬در ﺳـﻪ ﻣﺮﺣﻠـﻪ‬

‫‪ (Eura‬ﺗﺸﺨﻴﺺ داده ﺷﺪ‪ ،‬اﻧﺘﺨﺎب ﺷﺪﻧﺪ‪ 102 .‬ﻧﻔـﺮ ﺑـﻪ‬

‫اﻧﺠﺎم ﺷﺪ‪ .‬اﺑﺘﺪا ﻳﻚ دﻗﻴﻘﻪ در ‪ 94‬درﺟـﻪ ي ﺳـﺎﻧﺘﻲ ﮔـﺮاد‬

‫ﻋﻨﻮان ﮔﺮوه ﻣﻮرد و ‪ 103‬ﻧﻔـﺮ از اﻓـﺮادي ﻛـﻪ ﻣﺒـﺘﻼ ﺑـﻪ‬

‫ﺳﭙﺲ ‪ 60‬ﺛﺎﻧﻴﻪ در ‪ 84‬درﺟﻪ ي ﺳﺎﻧﺘﻲ ﮔﺮاد‪ 60 ،‬ﺛﺎﻧﻴـﻪ در‬

‫ﻣﻴﮕﺮن ﻧﺒﻮدﻧﺪ‪ ،‬ﺑﻪ ﻋﻨﻮان ﮔـﺮوه ﺷـﺎﻫﺪ اﻧﺘﺨـﺎب ﺷـﺪﻧﺪ‪.‬‬

‫‪ 72‬درﺟــﻪي ﺳــﺎﻧﺘﻲﮔــﺮاد و در ﻧﻬﺎﻳــﺖ ﭘــﻨﺞ دﻗﻴﻘــﻪ در‬

‫ﺳﻦ‪ ،‬ﺟﻨﺲ‪ ،‬وﺿﻌﻴﺖ اﻗﺘﺼﺎدي‪ -‬اﺟﺘﻤﺎﻋﻲ در دو ﮔـﺮوه‬

‫‪ 72‬درﺟﻪي ﺳﺎﻧﺘﻲﮔـﺮاد داﺧـﻞ ‪ Thermo cycler‬اﻧﺠـﺎم‬

‫ﻫﻤﺴﺎن ﺑﻮد‪ .‬ﺑﺮاي اﻓﺮاد ﻣﻮرد ﻣﻄﺎﻟﻌﻪ ﻳﻚ ﭼـﻚ ﻟﻴﺴـﺖ‬

‫ﺷﺪ‪ .‬اﻳﻦ ﭼﺮﺧﻪ ‪ 40‬ﻣﺮﺗﺒـﻪ ﺗﻜـﺮار ﮔﺮدﻳـﺪ‪ .‬ﺑﻌـﺪ از ﭘﺎﻳـﺎن‬

‫ﺷﺎﻣﻞ اﻃﻼﻋﺎت ﻣﺮﺑﻮط ﺑﻪ ﺳـﻦ‪ ،‬ﺟـﻨﺲ‪ ،‬ﺷـﻐﻞ‪ ،‬ﻣـﺪت‬

‫‪ PCR‬ﺑــﺮاي ﺗﻌﻴــﻴﻦ ﻧــﻮع اﻟــﻞ ‪ A‬و ‪ G‬از روش ‪HRM‬‬

‫زﻣﺎن اﺑﺘﻼ‪ ،‬ﻋﻼﻳﻢ ﻣﻴﮕﺮن‪ ،‬ﻧﻮع ﻣﻴﮕﺮن‪ ،‬دو ﻃﺮﻓﻪ ﻳﺎ ﻳـﻚ‬

‫اﺳﺘﻔﺎده ﺷﺪ‪.‬‬

‫ﻃﺮﻓﻪ ﺑﻮدن ﺳﺮ درد ﺗﻜﻤﻴﻞ ﺷﺪ‪ .‬از ﻫﺮ دو ﮔﺮوه ﭘـﺲ از‬

‫دادهﻫـﺎ وارد ﻧــﺮماﻓـﺰار آﻣــﺎري ‪ SPSS‬ﻧﺴــﺨﻪي ‪18‬‬

‫ﮔﺮﻓﺘﻦ رﺿﺎﻳﺖ ﻧﺎﻣﻪ ﺟﻬﺖ ﺷﺮﻛﺖ در ﻃﺮح ﺗﺤﻘﻴﻘﺎﺗﻲ ﺑﻪ‬

‫)‪ (version 18, SPSS Inc., Chicago, IL‬ﺷﺪ و ﺗﻮﺳﻂ‬

‫ﻣﻴــﺰان ‪ 2‬ﺳــﻲﺳــﻲ ﺧــﻮن ﺟﻬــﺖ اﺳــﺘﺨﺮاج ‪ DNA‬از‬

‫آزﻣﻮنﻫﺎي ‪ χ2‬و ‪ Logistic regression‬ﺗﺠﺰﻳﻪ و ﺗﺤﻠﻴـﻞ‬

‫ﻟﻜﻮﺳﻴﺖ ﻫﺎ ﮔﺮﻓﺘﻪ ﺷﺪ‪ .‬ﻧﻤﻮﻧﻪ ي ﺧـﻮن ﮔﺮﻓﺘـﻪ ﺷـﺪه در‬

‫ﮔﺮدﻳﺪ‪ .‬ﺑﺮاي ﺑﺮرﺳﻲ اﻳﻦ ﻛﻪ آﻳـﺎ ژﻧﻮﺗﻴـﭗ ﻣـﻮرد ﻧﻈـﺮ از‬

‫ﻟﻮﻟﻪ ﻫﺎي ﺣﺎوي ‪ EDTA‬ذﺧﻴﺮه و ﺗـﺎ زﻣـﺎن اﺳـﺘﻔﺎده در‬

‫ﺗﻌﺎدل ‪ Hardy-Weinberg‬ﭘﻴﺮوي ﻣﻲ ﻛﻨﺪ‪ ،‬ﺗﺴـﺖ آﻣـﺎري‬

‫‪ -20‬درﺟﻪي ﺳﺎﻧﺘﻲﮔﺮاد ﻧﮕﻬﺪاري ﺷﺪ‪.‬‬

‫‪ χ2‬اﺳــﺘﻔﺎده ﺷــﺪ و وﺟــﻮد راﺑﻄــﻪي ﺑــﻴﻦ ﭘﻠــﻲﻣﻮرﻓﻴﺴــﻢ‬

‫ﺑـــﺮاي اﺳـــﺘﺨﺮاج ‪ DNA‬از ﻛﻴـــﺖ اﺳـــﺘﺨﺮاج‬

‫‪ C677T‬و ﻣﻴﮕﺮن ﺑﺎ اﺳـﺘﻔﺎده از ‪ Logistic regression‬و‬

‫‪ Bio Genet‬ﺳﺎﺧﺖ ﻛﺸـﻮر ﻛـﺮه اﺳـﺘﻔﺎده ﺷـﺪ‪ .‬ﺗﻌﻴـﻴﻦ‬

‫ﺑﺎ ﻣﺤﺎﺳﺒﻪي ﻧﺴﺒﺖ ﺷـﺎﻧﺲ )‪ (OR‬ﺑـﺎ ﻓﺎﺻـﻠﻪي اﻃﻤﻴﻨـﺎن‬

‫ﭘﻠــﻲﻣﻮرﻓﻴﺴــﻢ ژﻧﺘﻴﻜــﻲ ‪ C677T‬در ژن ‪ MTHFR‬ﺑــﺎ‬

‫‪ 95‬درﺻﺪ )‪ (CI 95%‬ﻣﻮرد ﺑﺮرﺳﻲ ﻗﺮار ﮔﺮﻓﺖ‪ .‬در ﺗﻤﺎم‬

‫اﺳـــﺘﻔﺎده از ﺗﻜﻨﻴـــﻚ ‪time PCR HRM‬‬

‫‪Real‬‬

‫آﻧﺎﻟﻴﺰﻫﺎ ﻣﻴﺰان ‪ P < 0/05‬ﻣﻌﻨﻲدار در ﻧﻈﺮ ﮔﺮﻓﺘﻪ ﺷﺪ‪.‬‬

‫) ‪Polymerase chain reaction-High resolution‬‬

‫‪ (melting‬ﺑﺮرﺳﻲ ﺷﺪ‪.‬‬

‫ﻳﺎﻓﺘﻪﻫﺎ‬

‫ﺑﺮاي ﺗﻌﻴﻴﻦ ﭘﻠﻲﻣﻮرﻓﻴﺴﻢ ژﻧﺘﻴﻜـﻲ ‪ ،C677T‬ﻗﺴـﻤﺖ‬

‫در اﻳﻦ ﻣﻄﺎﻟﻌﻪ ﻓﺮاواﻧـﻲ ژﻧـﻮﺗﻴﭙﻲ ‪ C677T‬در دو ﮔـﺮوه‬

‫داراي ‪ 198‬ﺟﻔــﺖ ﺑــﺎز از ژن ‪ MTHFR‬را ﻛــﻪ داراي‬

‫ﻣﺒــﺘﻼ ﺑــﻪ ﻣﻴﮕــﺮن و ﺳــﺎﻟﻢ ﺑــﺎ اﺳــﺘﻔﺎده از ‪PCR-HRM‬‬

‫ﻣﺠﻠﻪ داﻧﺸﻜﺪه ﭘﺰﺷﻜﻲ اﺻﻔﻬﺎن – ﺳﺎل ‪ / 30‬ﺷﻤﺎره ‪ /214‬ﻫﻔﺘﻪ ﭼﻬﺎرم دي ‪1391‬‬ ‫‪www.mui.ac.ir‬‬

‫‪1937‬‬

‫ﭘﻠﻲﻣﻮرﻓﻴﺴﻢ ژﻧﺘﻴﻜﻲ ‪ C677T‬در ژن ‪ MTHFR‬در ﺑﻴﻤﺎران ﻣﺒﺘﻼ ﺑﻪ ﻣﻴﮕﺮن‬

‫ﻛﺎﻣﻴﺎر ﻫﻤﺖ و ﻫﻤﻜﺎران‬

‫ﻣﺸﺨﺺ ﮔﺮدﻳﺪ‪ .‬ﻛﻞ اﻓﺮاد ﻣﻮرد ﻣﻄﺎﻟﻌﻪ ‪ 203‬ﻧﻔﺮ ﺑﻮدﻧـﺪ‬

‫ﺧﺎص ﻣﻤﻜﻦ اﺳﺖ روي ﺑﻴﻤـﺎري ﻫـﺎ و راﺑﻄـﻪ ي آن ﻫـﺎ‬

‫ﻛﻪ ‪ 102‬ﻧﻔﺮ آن ﻫﺎ ﻣﺒـﺘﻼ ﺑـﻪ ﻣﻴﮕـﺮن و ‪ 101‬ﻧﻔـﺮ ﺳـﺎﻟﻢ‬

‫ﻣﺆﺛﺮ ﺑﺎﺷﻨﺪ ﻣﻨﻄﻘﻲ ﺑﻪ ﻧﻈﺮ ﻣـﻲ رﺳـﺪ‪ .‬ﺗـﺎﻛﻨﻮن ﻣﻄﺎﻟﻌـﺎت‬

‫ﺑﻮدﻧﺪ‪ .‬دو ﮔﺮوه ﺑﻴﻤﺎر و ﺳـﺎﻟﻢ از ﻟﺤـﺎظ ﺳـﻦ و ﺟـﻨﺲ‬

‫زﻳﺎدي راﺑﻄﻪي ﻣﺜﺒﺘﻲ ﺑﻴﻦ ژنﻫـﺎي ﻛﺎﻧﺪﻳـﺪ و ﻣﻴﮕـﺮن را‬

‫اﺧﺘﻼف ﻣﻌﻨﻲداري ﻧﺪاﺷﺘﻨﺪ )ﺟﺪول ‪.(1‬‬

‫ﻧﺸﺎن دادهاﻧﺪ‪.‬‬

‫ﻓﺮاواﻧﻲ ژﻧﻮﺗﻴﭗ ‪ TT‬در ﮔﺮوه ﺳـﺎﻟﻢ ‪ 5/9‬درﺻـﺪ و‬

‫ﺑــﻪ ﻃــﻮر ﺑﺮﺟﺴــﺘﻪ ﻧﺸــﺎن داده ﺷــﺪه اﺳــﺖ ﻛــﻪ‬

‫در ﮔــﺮوه ﺑﻴﻤــﺎر ‪ 3/9‬درﺻــﺪ ﺑــﻮد‪ ،‬اﻣــﺎ اﻳــﻦ اﺧــﺘﻼف‬

‫ﭘﻠﻲﻣﻮرﻓﻴﺴـﻢﻫـﺎي ‪،(Dopamine 2 receptor) DRD2‬‬

‫ﻣﻌﻨ ـﻲدار ﻧﺒــﻮد )‪،CI95%: 0/188-2/362 ،P = 0/530‬‬

‫‪beta-hydroxylase) DBH‬‬

‫‪ (Dopamin‬و ‪INSR‬‬

‫‪ .(OR = 0/667‬ﻓﺮاواﻧﻲ زﻧﻮﺗﻴﭗ ﻫﺎ در دو ﮔﺮوه ﻣﻮرد و‬

‫)‪ ،(Insulin receptor‬در اﺳﺘﻌﺪاد اﺑﺘﻼ ﺑﻪ ﻣﻴﮕـﺮن ﻧﻘـﺶ‬

‫ﺷﺎﻫﺪ در اﻳﻦ ﻣﻄﺎﻟﻌﻪ اﺧـﺘﻼف ﻣﻌﻨـﻲداري ﻧﺸـﺎن ﻧـﺪاد‬

‫دارﻧﺪ )‪.(15-16‬‬

‫)ﺟـــﺪول ‪ .(2‬ﻫﻤﭽﻨـــﻴﻦ ژﻧﻮﺗﻴـــﭗ ‪ C677T‬از ﺗﻌـــﺎدل‬

‫ﻋــﻼوه ﺑــﺮ اﺧــﺘﻼﻻت ﻧﻮروﻟــﻮژﻳﻜﻲ‪ ،‬ﺑــﻪ ﻟﺤــﺎظ‬

‫‪ Hardy-Weinberg‬ﭘﻴﺮوي ﻣﻲﻛﺮد )‪،d = 2 ،χ2 = 0/476‬‬

‫ﭘﺎﺗﻮﻓﻴﺰﻳﻠﻮژﻳﻜﻲ ﻣﻲﺗﻮان ﮔﻔﺖ ﻣﻴﮕﺮن در اﺛـﺮ ﺗﻐﻴﻴـﺮ در‬

‫‪.(P = 0/790‬‬

‫ﻛﺸﺶ رگﻫﺎ و ﺗﻐﻴﻴﺮ در ﺟﺮﻳﺎن ﺧﻮن ﻣﻐﺰي ﺑـﻪ وﺟـﻮد‬ ‫ﻣﻲآﻳﺪ )‪ .(17‬از اﻳـﻦ رو‪ ،‬ﻣﻜﺎﻧﻴﺴـﻢﻫـﺎي ﻣﻮﻟﻜـﻮﻟﻲ ﻛـﻪ‬

‫ﺑﺤﺚ‬

‫ﻧﻘﺶ ﻛﺎرﺑﺮدي در اﻧﺪوﺗﻠﻴﺎل رگ ﻫﺎ دارﻧﺪ ﺑﺎﻳﺪ ﺑﻪ ﻋﻨـﻮان‬

‫ﻣﻴﮕﺮن ﺑﻪ ﻋﻨﻮان ﻓﻨﻮﺗﻴﭙﻲ از اﺧﺘﻼﻻت ﭘﻠﻲ ژﻧـﻲ در ﻧﻈـﺮ‬

‫ﻳﻜﻲ از ﻣﻮارد ﻛﻠﻴﺪي در اﺳﺘﻌﺪاد اﺑﺘﻼ ﺑﻪ ﻣﻴﮕﺮن در ﻧﻈﺮ‬

‫ﮔﺮﻓﺘﻪ ﻣﻲ ﺷﻮد ﻛﻪ ﻣﻨﻌﻜﺲ ﻛﻨﻨﺪهي اﺛـﺮ ﭼﻨـﺪﻳﻦ ﺟﺎﻳﮕـﺎه‬

‫ﮔﺮﻓﺘﻪ ﺷﻮﻧﺪ‪ .‬ﻧﺸﺎن داده ﺷﺪه اﺳﺖ ﻛـﻪ اﻓـﺰاﻳﺶ ﻣﻴـﺰان‬

‫ژﻧﻲ ﻛﻪ ﻓﺮاﻳﻨﺪ ﻫﺎي ﭘﺎﺗﻮﻓﻴﺰﻳﻮﻟﻮژﻳﻜﻲ ﻣﺘﻔﺎوﺗﻲ را ﺗﻌـﺪﻳﻞ‬

‫ﻫﻤﻮﺳﻴﺘﺌﻴﻦ ﻣﻮﺟﻮد در ﮔﺮدش ﺧﻮن ﺑﺎﻋـﺚ آﺳـﻴﺐ ﺑـﻪ‬

‫ﻣﻲﻛﻨﺪ‪ ،‬ﻣﻲ ﺑﺎﺷﺪ‪ .‬ﺑﻨﺎﺑﺮاﻳﻦ اﻳﻦ ﻓﺮﺿﻴﻪ ﻛﻪ ﺑﻌﻀﻲ ژن ﻫﺎي‬

‫ﺳﻠﻮلﻫﺎ ﻣﻲﺷﻮد )‪.(18‬‬

‫ﺟﺪول ‪ .1‬اﻃﻼﻋﺎت دﻣﻮﮔﺮاﻓﻴﻚ ﺑﻴﻤﺎران و اﻓﺮاد ﺳﺎﻟﻢ ﻣﻮرد ﻣﻄﺎﻟﻌﻪ‬

‫ﺳﻦ )ﺳﺎل(‬ ‫ﺟﻨﺲ‬

‫*‬

‫ﻣﺒﺘﻼﻳﺎن ﺑﻪ ﻣﻴﮕﺮن‬

‫اﻓﺮاد ﺳﺎﻟﻢ‬

‫ﻣﻘﺪار ‪P‬‬

‫‪34/080 ± 9/737‬‬

‫‪34/77 ± 10/30‬‬

‫‪0/64‬‬

‫**‬

‫زن‬

‫)‪76 (82/6‬‬

‫)‪71 (78/0‬‬

‫ﻣﺮد‬

‫)‪16 (17/4‬‬

‫)‪20 (22/0‬‬

‫‪0/27‬‬

‫*‪ :‬اﻧﺤﺮاف ﻣﻌﻴﺎر ‪ ±‬ﻣﻴﺎﻧﮕﻴﻦ‬ ‫**‪) :‬درﺻﺪ( ﺗﻌﺪاد‬

‫ﺟﺪول ‪ .2‬ارﺗﺒﺎط ﺑﻴﻦ ﭘﻠﻲﻣﻮرﻓﻴﺴﻢ ژﻧﺘﻴﻜﻲ ‪ C677T‬و ﺑﻴﻤﺎري ﻣﻴﮕﺮن‬ ‫ﻣﺒﺘﻼﻳﺎن ﺑﻪ ﻣﻴﮕﺮن‬

‫اﻓﺮاد ﺳﺎﻟﻢ‬

‫‪OR‬‬

‫‪CC‬‬

‫)‪57 (55/9‬‬

‫)‪54 (53/5‬‬

‫‪1/000‬‬

‫ژﻧﻮﺗﻴﭗ‬

‫‪CI 95%‬‬

‫ﻣﻘﺪار ‪P‬‬

‫‪CT‬‬

‫)‪41 (40/2‬‬

‫)‪41 (40/6‬‬

‫‪1/056‬‬

‫‪0/728-1/532‬‬

‫‪0/776‬‬

‫‪TT‬‬

‫)‪4 (3/9‬‬

‫)‪6 (5/9‬‬

‫‪0/667‬‬

‫‪0/188-2/362‬‬

‫‪0/530‬‬

‫‪1938‬‬

‫ﻣﺠﻠﻪ داﻧﺸﻜﺪه ﭘﺰﺷﻜﻲ اﺻﻔﻬﺎن – ﺳﺎل ‪ / 30‬ﺷﻤﺎره ‪ /214‬ﻫﻔﺘﻪ ﭼﻬﺎرم دي ‪1391‬‬ ‫‪www.mui.ac.ir‬‬

‫ﭘﻠﻲﻣﻮرﻓﻴﺴﻢ ژﻧﺘﻴﻜﻲ ‪ C677T‬در ژن ‪ MTHFR‬در ﺑﻴﻤﺎران ﻣﺒﺘﻼ ﺑﻪ ﻣﻴﮕﺮن‬

‫ﻛﺎﻣﻴﺎر ﻫﻤﺖ و ﻫﻤﻜﺎران‬

‫ﻳﻚ ﻣﻄﺎﻟﻌﻪ ي ﻣﺘﺎآﻧﺎﻟﻴﺰي ﻛﻪ ﺑﻪ ﺗـﺎزﮔﻲ اﻧﺠـﺎم ﺷـﺪه‬

‫‪ TT‬و ﻣﻴﮕﺮن ﺑـﻪ ﺧﺼـﻮص ﻣﻴﮕـﺮن ﺑـﺎ ‪ Eura‬را ﻧﺸـﺎن‬

‫اﺳﺖ‪ ،‬ﻧﺸﺎن ﻣﻲ دﻫﺪ ﻛﻪ ﻣﻴـﺰان ﺑـﺎﻻﻳﻲ از ﻫﻤﻮﺳﻴﺴـﺘﺌﻴﻦ‬

‫دادﻧﺪ )‪ .(23-25‬ﻫﻤﭽﻨﻴﻦ در ﻣﻄﺎﻟﻌﻪ ي دﻳﮕﺮي ﻛﻪ اﻧﺠﺎم‬

‫ﻣﻲ ﺗﻮاﻧﺪ ﺑﻪ ﻋﻨﻮان ﻳﻚ ﻋﺎﻣﻞ ﺧﻄﺮ ﻫﻢ ﺑﺮاي ﺑﻴﻤﺎري ﻫﺎي‬

‫ﺷــﺪ‪ ،‬ارﺗﺒــﺎط ﻣﻌﻨــﻲداري ﺑــﻴﻦ آﻟــﻞ ‪ C677T‬در ژن‬

‫ﻗﻠﺒﻲ و ﻫﻢ ﻣﻐﺰي ﺑﺎﺷﺪ و ﭘﻴﺸﻨﻬﺎد ﻣـﻲﻛﻨـﺪ ﻛـﻪ ﻛـﺎﻫﺶ‬

‫‪ MTHFR‬و ﻣﻴﮕﺮن ﺑﺎ ‪ Eura‬در ﺑﻴﻤﺎران اﻓﺴـﺮده ﻧﺸـﺎن‬

‫ﻣﻘﺪار ﻫﻤﻮﺳﻴﺴـﺘﺌﻴﻦ ﺑـﻪ وﺳـﻴﻠﻪ ي ﻳـﻚ رژﻳـﻢ ﻏـﺬاﻳﻲ‬

‫داده ﺷﺪ )‪.(26‬‬

‫ﺳــﺎدهي ﻓــﻮﻻت ﻣــﻲﺗﻮاﻧــﺪ ﺧﻄــﺮ ﺑﻴﻤــﺎريﻫــﺎي‬

‫در ﻧﻬﺎﻳﺖ ﺑﺎ ﺗﻮﺟﻪ ﺑﻪ ﻣﻄﺎﻟﻌﻪ ﻫﺎي ﻗﺒﻠﻲ در اﻳﻦ زﻣﻴﻨﻪ‬

‫ﻗﻠﺒــﻲ‪ -‬ﻋﺮوﻗــﻲ را ﻛــﺎﻫﺶ ﺑﺪﻫــﺪ )‪ .(19‬ﻫﻤﭽﻨــﻴﻦ‬

‫ﻛﻪ راﺑﻄﻪ ﻫﺎي ﻣﻌﻨﻲ داري ﺑـﺎ ﻣﻴﮕـﺮن ﺑـﺎ ‪ Eura‬را ﻧﺸـﺎن‬

‫آزﻣﺎﻳﺸﺎت اﻧﺠﺎم ﺷﺪه روي ﻣﺪل ﺣﻴﻮاﻧﻲ ﭘﻴﺸﻨﻬﺎد ﻣﻲ ﻛﻨﺪ‬

‫دادهاﻧﺪ‪ ،‬در ﻣﻄﺎﻟﻌﻪي ﻣﺎ ﻫـﻴﭻ ارﺗﺒـﺎط ﻣﻌﻨـﻲداري دﻳـﺪه‬

‫ﻫﻴﭙﺮﻫﻤﻮﺳﻴﺴﺘﺌﻴﻨﻤﻲ ﻣﻤﻜﻦ اﺳﺖ اﺣﺘﻤﺎل اﺑﺘﻼ ﺑﻪ ﻣﻴﮕﺮن‬

‫ﻧﺸﺪ و ﻓﺮاواﻧﻲ ﻫﻤﻮزﻳﮕﻮت ‪ TT‬در ﮔﺮوه ﺑﻴﻤـﺎر ﺑﻴﺸـﺘﺮ‬

‫را ﺑﺎ اﻓـﺰاﻳﺶ ﺣﺴﺎﺳـﻴﺖ ﻋـﺮوق ﻣﻐـﺰي اﻓـﺰاﻳﺶ دﻫـﺪ‬

‫از ﺷﺎﻫﺪ ﻧﺒﻮد‪.‬‬

‫)‪ .(20‬ﻋﻼوه ﺑﺮ اﻳﻦ‪ ،‬ﻣﻘﺎدﻳﺮ ﺑﺎﻻي ﻫﻤﻮﺳﻴﺘﺌﻴﻦ در اﻓـﺮاد‬

‫در ﻣﻄﺎﻟﻌﻪ ي ﻣﺎ ﺑﻪ دﻟﻴـﻞ ﻣﺤـﺪودﻳﺖ ﺗﻌـﺪاد ﻧﻤﻮﻧـﻪ‪،‬‬

‫ﻣﺒﺘﻼ ﺑـﻪ ﻣﻴﮕـﺮن ﺑـﺎ ‪ Eura‬ﮔـﺰارش ﺷـﺪه اﺳـﺖ )‪.(21‬‬

‫ﺗﻌﺪاد اﻓﺮاد ﻣﺒﺘﻼ ﺑﻪ ﻣﻴﮕﺮن ﺑﺎ ‪ Eura‬ﺑﺴﻴﺎر ﻧﺎدر ﺑﻮد و ﺑﻪ‬

‫ﻣﻄﺎﻟﻌﻪي دﻳﮕﺮي ﻧﺸﺎن داده اﺳﺖ ﻛﻪ اﻟـﻞ ‪ 677T‬در ژن‬

‫ﻫﻤﻴﻦ دﻟﻴﻞ اﻣﻜﺎن اﻳﻦ ﻛﻪ ﺑﺘﻮان اﻳﻦ ﭘﻠﻲ ﻣﻮرﻓﻴﺴﻢ را ﺑـﻪ‬

‫‪ MTHFR‬ﺑﻪ ﻃﻮر ﻣﺴﺘﻘﻴﻢ ﺑﺎ ﻛـﺎﻫﺶ ﻓﻌﺎﻟﻴـﺖ آﻧـﺰﻳﻢ و‬

‫ﺗﻨﻬﺎﻳﻲ در ﻣﻴﮕﺮن ﻫـﺎي ﺑـﺎ ‪ Eura‬ﺑﺮرﺳـﻲ ﻛـﺮد‪ ،‬وﺟـﻮد‬

‫ژﻧﻮﺗﻴــﭗ ﻫﻤﻮزﻳﮕــﻮت ‪ TT‬ﺑــﻪ ﻃــﻮر ﻏﻴــﺮ ﻣﺴــﺘﻘﻴﻢ ﺑــﺎ‬

‫ﻧﺪاﺷﺖ‪.‬‬

‫ﻫﻴﭙﺮﻫﻤﻮﺳﻴﺴﺘﺌﻴﻨﻤﻲ در ارﺗﺒﺎط اﺳﺖ و ﻓﺮد را ﺑﻪ ﺳـﻤﺖ‬ ‫اﺑﺘﻼ ﺑﻴﻤﺎريﻫﺎي ﻋﺮوﻗﻲ ﻫﺪاﻳﺖ ﻣﻲﻛﻨﺪ )‪.(10‬‬

‫اﻳﻦ ﻣﻄﺎﻟﻌﻪ‪ ،‬اوﻟـﻴﻦ ﻣﻄﺎﻟﻌـﻪاي ﺑـﻮد ﻛـﻪ ﺑـﻪ ﺑﺮرﺳـﻲ‬ ‫ﻓﺮاواﻧﻲ اﻳﻦ ﭘﻠﻲ ﻣﻮرﻓﻴﺴﻢ در ﺟﻤﻌﻴﺖ اﻳﺮاﻧﻲ ﭘﺮداﺧـﺖ‪.‬‬

‫در اﻳﻦ ﻣﻄﺎﻟﻌﻪ ﻣـﺎ ﻓﺮاواﻧـﻲ اﻟـﻞ ‪ 677T‬را دو ﮔـﺮوه‬

‫ﭘﻴﺸﻨﻬﺎد ﻣﻲﺷﻮد ﻳﻚ ﻣﻄﺎﻟﻌﻪ ي ﻣﺸﺎﺑﻪ ﺑﺎ ﺗﻌـﺪاد ﻧﻤﻮﻧـﻪ ي‬

‫اﻓﺮاد ﻣﺒﺘﻼ ﺑﻪ ﻣﻴﮕﺮن و اﻓﺮاد ﺳﺎﻟﻢ ﺑﺎ ﻫﻢ ﻣﻘﺎﻳﺴﻪ ﻛـﺮدﻳﻢ‬

‫ﺑﻴﺸﺘﺮ اﻧﺠﺎم ﺷﻮد‪ ،‬ﻫﻤﭽﻨﻴﻦ ﻣﻮارد اﺑﺘﻼ ﺑـﻪ ﻣﻴﮕـﺮن ﺑـﺎ و‬

‫ﻛﻪ ﻫﻴﭻ اﺧﺘﻼف ﻣﻌﻨﻲ داري در اﻳﻦ دو ﮔﺮوه دﻳﺪه ﻧﺸﺪ‪.‬‬

‫ﺑﺪون ‪ Eura‬را ﺟﺪاﮔﺎﻧﻪ ﺑﺮرﺳﻲ ﻛﻨﺪ‪.‬‬

‫در ﻣﻄﺎﻟﻌﻪ اي ﻛـﻪ ﺗﻮﺳـﻂ ‪ Lea‬و ﻫﻤﻜـﺎران اﻧﺠـﺎم ﺷـﺪ‬ ‫راﺑﻄﻪي ﻣﻌﻨﻲداري ﺑﻴﻦ ﭘﻠﻲﻣﻮرﻓﻴﺴﻢ ‪ C677T‬و ﻣﻴﮕـﺮن‬

‫ﺗﺸﻜﺮ و ﻗﺪرداﻧﻲ‬

‫ﺑﺎ ‪ Eura‬دﻳﺪه ﺷﺪ )‪ .(22‬در اﻳﻦ ﻣﻄﺎﻟﻌﻪ ﻓﺮاواﻧﻲ ژﻧﻮﺗﻴﭗ‬

‫ﺑــﺎ ﺗﺸــﻜﺮ از زﺣﻤــﺎت ﺳــﺮﻛﺎر ﺧــﺎﻧﻢ ﻧﺴــﺮﻳﻦ ﺻــﺎﺑﺮي‬

‫‪ TT‬در ﮔﺮوه ﺑﻴﻤﺎران ﻣﺒـﺘﻼ ﺑـﻪ ﻣﻴﮕـﺮن ﺑﻴﺸـﺘﺮ از اﻓـﺮاد‬

‫ﺷﻬﺮﺑﺎﺑﻜﻲ ﻛﻪ در ﺗﻬﻴﻪ و ﺗﺪوﻳﻦ اﻳﻦ ﻣﻘﺎﻟـﻪ ﻣـﺎ را ﻳـﺎري‬

‫ﺳﺎﻟﻢ ﺑﻮد‪ .‬ﭼﻨﺪﻳﻦ ﻣﻄﺎﻟﻌﻪ ارﺗﺒﺎط ﻣﻌﻨﻲ داري ﺑﻴﻦ ژﻧﻮﺗﻴﭗ‬

‫ﻧﻤﻮدﻧﺪ‪.‬‬

‫‪Zvan B. Associations between cerebral and‬‬ ‫‪systemic endothelial function in migraine‬‬ ‫;‪patients: a post-hoc study. BMC Neurol 2011‬‬ ‫‪11: 146.‬‬ ‫‪4. Levy D, Burstein R, Strassman AM. Mast cell‬‬ ‫‪involvement in the pathophysiology of migraine‬‬ ‫;‪headache: A hypothesis. Headache 2006‬‬

‫‪1. Brandes JL. Migraine in women. Continuum‬‬ ‫‪(Minneap Minn ) 2012; 18(4): 835-52.‬‬ ‫‪2. Peterlin BL, Calhoun AH, Balzac F. Men,‬‬ ‫‪women, and migraine: the role of sex, hormones,‬‬ ‫‪obesity, and PTSD. J Fam Pract 2012; 61(4‬‬ ‫‪Suppl): S7-11.‬‬ ‫‪3. Perko D, Pretnar-Oblak J, Sabovic M, Zaletel M,‬‬

‫‪References‬‬

‫ﻣﺠﻠﻪ داﻧﺸﻜﺪه ﭘﺰﺷﻜﻲ اﺻﻔﻬﺎن – ﺳﺎل ‪ / 30‬ﺷﻤﺎره ‪ /214‬ﻫﻔﺘﻪ ﭼﻬﺎرم دي ‪1391‬‬ ‫‪www.mui.ac.ir‬‬

‫‪1939‬‬

‫ﻛﺎﻣﻴﺎر ﻫﻤﺖ و ﻫﻤﻜﺎران‬

‫ در ﺑﻴﻤﺎران ﻣﺒﺘﻼ ﺑﻪ ﻣﻴﮕﺮن‬MTHFR ‫ در ژن‬C677T ‫ﭘﻠﻲﻣﻮرﻓﻴﺴﻢ ژﻧﺘﻴﻜﻲ‬

46(Suppl 1): S13-S18. 5. Dalkara T, Nozari A, Moskowitz MA. Migraine aura pathophysiology: the role of blood vessels and microembolisation. Lancet Neurol 2010; 9(3): 309-17. 6. Devor WN, Napoli R ,Sacca L. Vascular smooth muscle cell dysfunction in patients with migraine. Neurology 2010; 74(1): 94. 7. Tietjen GE, Herial NA, White L, Utley C, Kosmyna JM, Khuder SA. Migraine and biomarkers of endothelial activation in young women. Stroke 2009; 40(9): 2977-82. 8. Goyette P, Sumner JS, Milos R, Duncan AM, Rosenblatt DS, Matthews RG, et al. Human methylenetetrahydrofolate reductase: isolation of cDNA, mapping and mutation identification. Nat Genet 1994; 7(2): 195-200. 9. Heux S, Morin F, Lea RA ,Ovcaric M, Tajouri L, Griffiths LR. The methylentetrahydrofolate reductase gene variant (C677T) as a risk factor for essential hypertension in Caucasians. Hypertens Res 2004; 27(9): 663-7. 10. Frosst P, Blom HJ, Milos R, Goyette P, Sheppard CA, Matthews RG, et al. A candidate genetic risk factor for vascular disease: a common mutation in methylenetetrahydrofolate reductase. Nat Genet 1995; 10(1): 111-3. 11. Graham IM, O'Callaghan P. Vitamins, homocysteine and cardiovascular risk. Cardiovasc Drugs Ther 2002; 16(5): 383-9. 12. Hering-Hanit R, Friedman Z, Schlesinger I, Ellis M. Evidence for activation of the coagulation system in migraine with aura. Cephalalgia 2001; 21(2): 137-9. 13. Parsons AA, Strijbos PJ. The neuronal versus vascular hypothesis of migraine and cortical spreading depression. Curr Opin Pharmacol 2003; 3(1): 73-7. 14. Das UN. Folic acid says NO to vascular diseases. Nutrition 2003; 19(7-8): 686-92. 15. Peroutka SJ, Wilhoit T, Jones K. Clinical susceptibility to migraine with aura is modified by dopamine D2 receptor (DRD2) NcoI alleles. Neurology 1997; 49(1): 201-6. 16. Lea RA, Dohy A, Jordan K, Quinlan S, Brimage PJ, Griffiths LR. Evidence for allelic association of the dopamine beta-hydroxylase gene (DBH) with susceptibility to typical migraine.

Neurogenetics 2000; 3(1): 35-40. 17. Goadsby PJ. Current concepts of the pathophysiology of migraine. Neurol Clin 1997; 15(1): 27-42. 18. Harker LA, Ross R, Slichter SJ, Scott CR. Homocystine-induced arteriosclerosis .The role of endothelial cell injury and platelet response in its genesis. J Clin Invest 1976; 58(3): 731-41. 19. Mei W, Rong Y, Jinming L, Yongjun L, Hui Z. Effect of homocysteine interventions on the risk of cardiocerebrovascular events: a meta-analysis of randomised controlled trials. Int J Clin Pract 2010; 64(2): 208-15. 20. Storer RJ, Goadsby PJ. Microiontophoretic application of serotonin (5HT)1B/1D agonists inhibits trigeminal cell firing in the cat. Brain 1997; 120 (Pt 12): 2171-7. 21. Evers S, Koch HG, Grotemeyer KH, Lange B, Deufel T, Ringelstein EB. Features, symptoms, and neurophysiological findings in stroke associated with hyperhomocysteinemia. Arch Neurol 1997; 54(10): 1276-82. 22. Lea RA, Ovcaric M, Sundholm J, MacMillan J, Griffiths LR. The methylenetetrahydrofolate reductase gene variant C677T influences susceptibility to migraine with aura. BMC Med 2004; 2: 3. 23. . Oterino A, Valle N, Bravo Y, Munoz P, Sanchez-Velasco P, Ruiz-Alegria C, et al. MTHFR T677 homozygosis influences the presence of aura in migraineurs. Cephalalgia 2004; 24(6): 491-4. 24. Goyette P, Sumner JS, Milos R, Duncan AM, Rosenblatt DS, Matthews RG, et al. Human methylenetetrahydrofolate reductase: isolation of cDNA mapping and mutation identification. Nat Genet 1994; 7(4): 551. 25. Gilbody S, Lewis S, Lightfoot T. Methylenetetrahydrofolate reductase (MTHFR) genetic polymorphisms and psychiatric disorders: a HuGE review. Am J Epidemiol 2007; 165(1): 1-13. 26. Samaan Z, Gaysina D, Cohen-Woods S, Craddock N, Jones L, Korszun A, et al. Methylenetetrahydrofolate reductase gene variant (MTHFR C677T) and migraine: a case control study and meta-analysis. BMC Neurol 2011; 11: 66.

1391 ‫ ﻫﻔﺘﻪ ﭼﻬﺎرم دي‬/214 ‫ ﺷﻤﺎره‬/ 30 ‫ﻣﺠﻠﻪ داﻧﺸﻜﺪه ﭘﺰﺷﻜﻲ اﺻﻔﻬﺎن – ﺳﺎل‬ www.mui.ac.ir

1940

Journal of Isfahan Medical School

Original Article

Vol. 30, No. 214, 4th week, January 2013

Received: 7.9.2012

Accepted: 10.11.2012

Genetic Polymorphisms of C677T MTHFR Gene in Migraine Patients Compared with Controls Kamyar Hemat1, Shaghayegh Haghjooy Javanmard MD, PhD2, Mohammad Saadatnia MD3, Laleh Rafiee4, Alireza Zandifar1, Mohamadhasan Tajaddini5

Abstract Background: Migraine is considered the end phenotype of a number of polygenic disorders reflecting the influence of several genetic loci modulating different pathophysiological processes. It has been shown that the 677T allele in methylenetetrahydrofolate reductase (MTHFR) gene is directly correlated with decreased enzymatic activity, and the T/T genotype is indirectly associated with mild hyperhomocysteinaemia which possibly leads to vascular disease. In this case-control study we investigated the association between C677T MTHFR polymorphisms and migraine in an Iranian population. Methods: A total of 205 cases and controls were enrolled to the study. The MTHFR C677T variant was genotyped in 102 unrelated migraine cases and 103 controls by HRM-PCR technique. Findings: There was no significant association between C677T MTHFR polymorphism and migraine in our study. The frequency of TT genotype was not higher in case group compared with the controls (OR = 0.667, 95% CI: 0.188-2.362, P = 0.530). Conclusion: The C677T variant in the MTHFR gene did not influence susceptibility to migraine in our study population. A more reliable conclusion may be drawn from investigations with larger sample size and separated migraine groups, with and without aura. Keywords: Genetic polymorphism, Migraine disorders, Methylenetetrahydrofolate reductase

* This paper is derived from a medical doctorate thesis in Isfahan University of Medical Sciences. 1

Student of Medicine, School of Medicine AND Student Research Committee, Isfahan University of Medical Sciences, Isfahan, Iran Associate Professor, Physiology Research Center, Isfahan University of Medical Sciences, Isfahan, Iran Associate Professor, Neuroscience Research Center AND Department of Neurology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran 4 Physiology Research Center, Isfahan University of Medical Sciences, Isfahan, Iran 5 MSc Student, Physiology Research Center AND Department of Biochemistry, School of Pharmacy AND Isfahan Pharmaceutical Research Center, Isfahan University of Medical Sciences, Isfahan, Iran Corresponding Author: Mohamadhasan Tajaddini, Email: [email protected] 2 3

1941

1391 ‫ ﻫﻔﺘﻪ ﭼﻬﺎرم دي‬/214 ‫ ﺷﻤﺎره‬/ 30 ‫ﻣﺠﻠﻪ داﻧﺸﻜﺪه ﭘﺰﺷﻜﻲ اﺻﻔﻬﺎن – ﺳﺎل‬ www.mui.ac.ir