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Newfound genetic clue to HIV rate in blacks

by Sabin Rus­sell, Chron­i­cle Med­ical Writer
San Fran­cis­co Chron­i­cle

SAN FRANCISCO — An inter­na­tion­al team of AIDS sci­en­tists has dis­cov­ered that a gene vari­ant com­mon in blacks pro­tects against cer­tain types of malar­ia but increas­es sus­cep­ti­bil­i­ty to HIV infec­tion by 40 per­cent.

Researchers, keen to find some bio­log­i­cal clues to explain why peo­ple of African descent are bear­ing a dis­pro­por­tion­ate share of the world’s AIDS cas­es, sus­pect this sub­tle genet­ic trait — found in 60 per­cent of Amer­i­can blacks and 90 per­cent of Africans — might part­ly explain the dif­fer­ence.

Ten per­cent of the world’s pop­u­la­tion lives in sub-Saha­ran Africa, but that region accounts for 70 per­cent of the men, women and chil­dren liv­ing with HIV infec­tion. In the Unit­ed States, African Amer­i­cans make up 12 per­cent of the pop­u­la­tion but account for half of new­ly diag­nosed HIV infec­tions.

“The cause of this imbal­ance is not nec­es­sar­i­ly dri­ven by behav­ior,” said Phill Wil­son, founder of the Black AIDS Insti­tute in Los Ange­les. “Gay black men do not engage in riski­er behav­ior than gay white men, for exam­ple. African peo­ple with this gene may have a high­er vul­ner­a­bil­i­ty.”

Based on their analy­sis, the researchers esti­mat­ed that this gene vari­ant alone may account for 11 per­cent of the esti­mat­ed 25 mil­lion HIV infec­tions that have occurred in sub-Saha­ran Africa — rough­ly 2.7 mil­lion cas­es.

The gene study was led by Dr. Sunil Ahu­ja, a pro­fes­sor of infec­tious dis­eases at the Uni­ver­si­ty of Texas Health Sci­ence Cen­ter at San Anto­nio, and pub­lished Wednes­day in the jour­nal Cell Host & Microbe.
Find­ing the Duffy pro­tein

Work­ing in col­lab­o­ra­tion with renowned virol­o­gist Robin Weiss of Uni­ver­si­ty Col­lege in Lon­don, the group zeroed in on a pro­tein found on the sur­face of red blood cells. It is known in lab­o­ra­to­ry cir­cles as the “Duffy anti­gen.”

Cer­tain species of malar­ia par­a­sites latch on to the Duffy pro­tein and use it as a gate­way to enter red blood cells. Africans over­whelm­ing­ly car­ry a gene that dis­ables this gate­way — and Weiss believes this may have been the result of an evo­lu­tion­ary bat­tle between humans and malar­ia. The genet­ic trait is also preva­lent among African Amer­i­cans, who typ­i­cal­ly car­ry a mix­ture of African and Euro­pean blood­lines.

“If there is no Duffy there, the malar­ia par­a­site can’t get in,” said Weiss.

In the 20th cen­tu­ry, how­ev­er, the Duffy pro­tein appears to have tak­en on anoth­er role, seem­ing to absorb HIV par­ti­cles, like a sponge, the researchers said. By sop­ping up the virus, the pro­tein ham­pers the virus’ chances of invad­ing vul­ner­a­ble white blood cells — the first step in HIV infec­tion.

Peo­ple with a dis­abled Duffy pro­tein — most Africans, for exam­ple — may there­fore be more vul­ner­a­ble to infec­tion.

Ahu­ja’s team com­pared 814 African Amer­i­can mil­i­tary per­son­nel who were HIV neg­a­tive with 470 who were infect­ed with HIV. Out of this com­par­i­son, the researchers found a 40 per­cent high­er risk of HIV among those whose genes sup­pressed the Duffy pro­tein.

The researchers also made anoth­er remark­able find­ing — once a per­son with the African gene becomes infect­ed, the same genet­ic trait appears to pro­long sur­vival. One of the Duffy pro­tein’s nat­ur­al roles appears to be to ramp up the immune sys­tem. It attracts a num­ber of chem­i­cal sig­nals that pro­mote inflam­ma­tion — a defen­sive mech­a­nism that nor­mal­ly pro­tects the body, but lays out a ban­quet of white blood cells for HIV to infect and destroy.

So the same genet­ic muta­tion that rais­es the risk of HIV infec­tion pro­vides some pro­tec­tion to those who become infect­ed. Sim­i­lar­ly, those who car­ry the nor­mal Duffy pro­tein may be some­what shield­ed from HIV infec­tion, but once infect­ed may sick­en and die soon­er with­out treat­ment. “There is a high order of com­plex­i­ty here,” Ahu­ja con­ced­ed.

Although Ahu­ja and his team are high­ly respect­ed researchers, some sci­en­tists in the field cau­tioned that the con­clu­sions may be pre­ma­ture. “I’m a lit­tle skep­ti­cal about it,” said Cheryl Win­kler, head of the Lab­o­ra­to­ry of Genom­ic Diver­si­ty at the Nation­al Can­cer Insti­tute, in Fred­er­ick, Md.
More study urged

Win­kler, an expert in genet­ic fac­tors that cause dis­ease, said the dif­fer­ences in infec­tion rates between sol­diers who car­ried the gene vari­ant and those who did not was sta­tis­ti­cal­ly sig­nif­i­cant, but bare­ly so. “They have a mod­el here, but they don’t have enough evi­dence,” she said. “This def­i­nite­ly requires more study and repli­ca­tion of results before you can make these assump­tions.”

UCSF Pro­fes­sor Dr. Warn­er Greene, direc­tor of the Glad­stone Insti­tute of Virol­o­gy in San Fran­cis­co, said the new study is intrigu­ing and presents a por­trait of the evo­lu­tion­ary strug­gle between humans and pathogens. “In response to the threat of malar­ia, you may be set up to become more sus­cep­ti­ble to HIV,” he said.

At a deep­er lev­el, he said, the study opens doors for new research into the com­plex rela­tion­ship between blood cells and the chem­i­cal sig­nals that turn the immune sys­tem on and off.

“They’ve done a real good job of try­ing to explain their results,” said UCSF virol­o­gist Dr. Jay Levy, who was among the first to iso­late HIV as the cause of AIDS. “It pos­es a nice chal­lenge to researchers try­ing to under­stand how HIV caus­es dis­ease.“
How the study was done

To find out if peo­ple car­ry­ing the malar­ia-pro­tec­tive gene might be more vul­ner­a­ble to HIV, researchers drew on a unique cohort of exper­i­men­tal sub­jects — U.S. Air Force per­son­nel whose blood has been col­lect­ed and stored for 25 years.

The Wil­ford Hall Med­ical Cen­ter cohort is a valu­able resource for genet­ic research because mil­i­tary per­son­nel live in sim­i­lar envi­ron­ments (mil­i­tary bases), work for the same employ­er (the Air Force), have sim­i­lar incomes and the same health care. Those sim­i­lar­i­ties make it eas­i­er for researchers to pin­point dif­fer­ences unlike­ly to be caused by social or envi­ron­men­tal fac­tors.

In this study, researchers com­pared 814 African Amer­i­can mil­i­tary per­son­nel who were HIV-neg­a­tive with 470 who were infect­ed with HIV.

They also screened those air­men to find if they car­ried the Duffy pro­tein. Out of this com­par­i­son popped the sur­pris­ing num­ber: A 40 per­cent high­er risk of HIV among those whose genes sup­pressed the Duffy pro­tein — a trait that pre­sum­ably evolved in Africa as a defense against malar­ia.
By the num­bers

The AIDS epi­dem­ic dis­pro­por­tion­ate­ly affects peo­ple of African descent.


of new HIV cas­es in the Unit­ed States are diag­nosed in African Amer­i­cans, who make up 12 per­cent of the pop­u­la­tion.


of the world’s pop­u­la­tion lives in sub-Saha­ran Africa.


of the world’s HIV/AIDS cas­es are in sub-Saha­ran Africa.

Sources: Cen­ters for Dis­ease Con­trol and Pre­ven­tion; UNAIDS


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