mtDNA Lineages Reveal Coronary Artery Disease-Associated Structures in the Lebanese Population

作者：Haber Marc; Youhanna Sonia C; Balanovsky Oleg; Saade Stephanie; Martinez Cruz Begona; Ghassibe Sabbagh Michella; Shasha Nabil; Osman Raed; el Bayeh Hamid; Koshel Sergey; Zaporozhchenko Valery; Balanovska Elena; Soria Hernanz David F; Platt Daniel E; Zalloua Pierre A^*

来源：Annals of Human Genetics, 2012, 76: 1-8.

DOI：10.1111/j.1469-1809.2011.00682.x

• Coronary artery disease
• HVS-1
• Lebanon
• mtDNA haplotype
• population structure

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 = 1.5035.30, 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%26apos;s r= 0.316, P %26lt; 0.001) than between haplogroup A and CAD (r= 0.149, P %26lt; 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.

• 出版日期2012-1