TY - JOUR
T1 - mtDNA Lineages Reveal Coronary Artery Disease-Associated Structures in the Lebanese Population
AU - Haber, Marc
AU - Youhanna, Sonia C.
AU - Balanovsky, Oleg
AU - Saade, Stephanie
AU - Martínez-Cruz, Begoña
AU - Ghassibe-Sabbagh, Michella
AU - Shasha, Nabil
AU - Osman, Raed
AU - el Bayeh, Hamid
AU - Koshel, Sergey
AU - Zaporozhchenko, Valery
AU - Balanovska, Elena
AU - Soria-Hernanz, David F.
AU - Platt, Daniel E.
AU - Zalloua, Pierre A.
PY - 2012/1
Y1 - 2012/1
N2 - Population origins and ancestry have previously been found to be important determinants of coronary artery disease (CAD). This study investigates associations of Lebanese mitochondrial DNA lineages with CAD and studies their correlation with other populations, exploring population structures that may infer mitochondria functional associations and reveal population movements and origins. Sequencing the mitochondrial hypervariable sequence 1 (HVS-1) of 363 controls and 448 cases revealed that haplogroup W was more frequent (P= 0.013) in cases compared to controls, and was associated with increased risk of CAD (OR = 5.50, 95% CI = 1.50-35.30, P= 0.026) among Lebanese samples. Haplogroup A was only found in controls (P= 0.029). We have detected stronger geographic correlation between haplogroup W and CAD (Pearson's r= 0.316, P < 0.001) than between haplogroup A and CAD (r= 0.149, P < 0.001). HVS-1 phylogenetic network of haplogroup W shows controls are restricted to European clusters while cases belong mostly to Middle Eastern natives. The network of haplogroup A shows that the controls belong to a cluster dominated by Central Asians. Our results show evidence of a gene flow into Lebanon, creating CAD-associated population structures that are similar to those in the source populations, maintained by limited admixture, and probably encompassing variations on the nuclear and/or the mitochondrial genome that are correlated with the disease.
AB - Population origins and ancestry have previously been found to be important determinants of coronary artery disease (CAD). This study investigates associations of Lebanese mitochondrial DNA lineages with CAD and studies their correlation with other populations, exploring population structures that may infer mitochondria functional associations and reveal population movements and origins. Sequencing the mitochondrial hypervariable sequence 1 (HVS-1) of 363 controls and 448 cases revealed that haplogroup W was more frequent (P= 0.013) in cases compared to controls, and was associated with increased risk of CAD (OR = 5.50, 95% CI = 1.50-35.30, P= 0.026) among Lebanese samples. Haplogroup A was only found in controls (P= 0.029). We have detected stronger geographic correlation between haplogroup W and CAD (Pearson's r= 0.316, P < 0.001) than between haplogroup A and CAD (r= 0.149, P < 0.001). HVS-1 phylogenetic network of haplogroup W shows controls are restricted to European clusters while cases belong mostly to Middle Eastern natives. The network of haplogroup A shows that the controls belong to a cluster dominated by Central Asians. Our results show evidence of a gene flow into Lebanon, creating CAD-associated population structures that are similar to those in the source populations, maintained by limited admixture, and probably encompassing variations on the nuclear and/or the mitochondrial genome that are correlated with the disease.
KW - Coronary artery disease
KW - HVS-1
KW - Lebanon
KW - MtDNA haplotype
KW - Population structure
UR - http://www.scopus.com/inward/record.url?scp=84155164030&partnerID=8YFLogxK
U2 - 10.1111/j.1469-1809.2011.00682.x
DO - 10.1111/j.1469-1809.2011.00682.x
M3 - Article
C2 - 22017296
AN - SCOPUS:84155164030
SN - 0003-4800
VL - 76
SP - 1
EP - 8
JO - Annals of Human Genetics
JF - Annals of Human Genetics
IS - 1
ER -