Ficolins are pattern recognition molecules that are involved in innate immune defense. Ficonin-2 (FCN2) has a specific affinity for lipoteichoic acid present in the cell wall of Streptococcus pyogenes, an etiological agent for rheumatic heart disease (RHD). We have estimated FCN2 serum levels and analyzed the functional variants of FCN2 in 400 RHD patients, 617 healthy controls, and 581 individuals belonged to various ethnic populations, who are inhabited in various geographical regions of India. Our study revealed that the FCN2 −986A and +6359T alleles were the risk factors for RHD susceptibility (p = 0.0007 for −986G>A; p = 0.0004 for +6359C>T). The haplotype AGGT (p = 0.0024) was observed to be a risk factor for RHD susceptibility, and the haplotype GGAC (p = 0.002) was found to confer protection against RHD. The level of serum FCN2 was significantly higher in controls (p < 0.0001) and in controls with GGAC haplotypes (p < 0.0001). The frequency of the risk alleles −986A and +6359T was found to be more prevalent in Northern and North-Western (Indo-European) India. The protective GGAC haplotype was found more prevalent in Eastern (Tibeto-Burman) and South-Western (Dravidian) India. Alleles −986A and +6359T were in positive correlation with the prevalence of RHD (regression coefficient = 1.84 and 1.94, respectively), whereas GGAC haplotype was in negative correlation with prevalence of RHD (regression coefficient = −1.71). In conclusion, we found that low level of serum ficolin-2 is significantly associated with RHD. Further, FCN2 −986A and +6359T alleles and AGGT haplotype are associated with increased susceptibility to RHD, while GGAC haplotype is associated with moderate protection against RHD.

中文翻译：

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新型 FCN2 变体和单倍型与风湿性心脏病有关

Ficolins 是参与先天免疫防御的模式识别分子。Ficonin-2 (FCN2) 对存在于化脓性链球菌（风湿性心脏病 (RHD) 的病原体）细胞壁中的脂磷壁酸具有特异性亲和力。我们估计了 FCN2 血清水平，并分析了400 名 RHD 患者、617 名健康对照者和 581 名不同种族人群中FCN2的功能变异，这些人居住在印度的不同地理区域。我们的研究表明FCN2 -986A 和 +6359T 等位基因是 RHD 易感性的危险因素（ -986G>A p = 0.0007； +6359C>T p = 0.0004）。单倍型 AGGT ( p = 0.0024) 被观察到是 RHD 易感性的危险因素，并且发现单倍型 GGAC ( p  = 0.002) 可提供针对 RHD 的保护。血清 FCN2 水平在对照组 ( p  < 0.0001) 和具有 GGAC 单倍型的对照组 ( p < 0.0001)。发现风险等位基因 -986A 和 +6359T 的频率在印度北部和西北部（印欧）更为普遍。发现保护性 GGAC 单倍型在印度东部（藏缅）和西南（德拉威）印度更为普遍。等位基因-986A 和+6359T 与RHD 的患病率呈正相关（回归系数分别为1.84 和1.94），而GGAC 单倍型与RHD 的患病率呈负相关（回归系数= -1.71）。总之，我们发现低水平的血清 ficolin-2 与 RHD 显着相关。此外，FCN2 -986A 和 +6359T 等位基因和 AGGT 单倍型与增加的 RHD 易感性相关，而 GGAC 单倍型与对 RHD 的中度保护相关。